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1.  Assessment of Antiobesity Potential of Achyranthes aspera Linn. Seed 
The present study was designed to evaluate the quality control parameters, quantitative phytochemical analysis (total phenols, total flavonoids, and total saponin content), and the antiobesity effect of ethanol extract of Achyranthes aspera Linn. seed (EAA) by employing in vitro and in vivo models. In in vitro study, the inhibitory activity of EAA on pancreatic amylase and lipase was measured. The in vivo pancreatic lipase activity was evaluated by measurement of plasma triacylglycerol levels after oral administration of EAA along with lipid emulsion to Swiss albino mice. The EAA inhibited pancreatic amylase and lipase activity in vitro and elevations of plasma triacylglycerol level in mice. Furthermore, the antiobesity effect of EAA (900 mg/kg) was assessed in mice fed a high-fat diet with or without EAA for 6 weeks. EAA significantly suppressed the increase in body, retroperitoneal adipose tissue, liver weights, and serum parameters, namely; total cholesterol, total triglyceride, and LDL-cholesterol level. The anti obesity effects of EAA in high-fat-diet-treated mice may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic amylase and lipase activity. Histopathological effects of EAA on the liver of mice were also assessed.
doi:10.1155/2012/715912
PMCID: PMC3418711  PMID: 22919417
2.  Anti-obesity effects of chikusetsusaponins isolated from Panax japonicus rhizomes 
Background
The rhizomes of Panax japonicus are used as a folk medicine for treatment of life-style related diseases such as arteriosclerosis, hyperlipidemia, hypertension and non-insulin-dependent diabetes mellitus as a substitute for ginseng roots in China and Japan. Obesity is closely associated with life-style-related diseases. This study was performed to clarify whether chikusetsusaponins prevent obesity induced in mice by a high-fat diet for 9 weeks.
Methods
We performed two in vivo experiments. In one, female ICR mice were fed a high-fat diet with or without 1 or 3% chikusetsusaponins isolated from P. japonicus rhizomes for 9 weeks. In the other, lipid emulsion with or without chikusetsusaponins was administered orally to male Wistar rats, and then the plasma triacylglycerol level was measured 0.5 to 5 h after the orally administered lipid emulsion. For in vitro experiments, the inhibitory effects of total chikusetsusaponins and various purified chikusetsusaponins on pancreatic lipase activity were determined by measuring the rate of release of oleic acid from triolein in an assay system using triolein emulsified with lecithin.
Results
Total chikusetsusaponins prevented the increases in body weight and parametrial adipose tissue weight induced by a high-fat diet. Furthermore, consumption of a high-fat diet containing 1 or 3% total chikusetsusaponins significantly increased the fecal content and triacylglycerol level at day 3 compared with the high-fat diet groups. Total chikusetsusaponins inhibited the elevation of the plasma triacylglycerol level 2 h after the oral administration of the lipid emulsion. Total chikusetsusaponins, chikusetsusaponin III, 28-deglucosyl-chikusetsusaponin IV and 28-deglucosyl-chikusetsusaponin V inhibited the pancreatic lipase activity.
Conclusion
The anti-obesity effects of chikusetsusaponins isolated from P. japonicus rhizomes in mice fed a high-fat diet may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity. The present study clearly indicated that the saponin fractions of P. japonicus rhizomes had a significant anti-obesity action and supports the traditional usage as a substitute drug for ginseng roots.
doi:10.1186/1472-6882-5-9
PMCID: PMC1097713  PMID: 15811191
3.  Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor 
Background
There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model.
Methods
We determined the inhibitory action of Anti-lipase IgY on lipase activity in vitro. We also focused our evaluation on the anti-obesity properties of Anti-lipase IgY in a murine high fat diet-induced obesity model.
Results
Anti-lipase IgY blocked porcine lipase activity with an IC50 of 0.49 μM. Supplementing the high fat diet with only 0.2% (w/w) of Anti-lipase IgY for 35 days significantly decreased the weights of intraperitoneal adipose tissues, epididymal, mesenteric, retroperitoneal and perirenal adipose tissues, and the amounts of hepatic total lipid, triglyceride, and cholesterol. This was accompanied by a significant increase in the fecal excretion of triglyceride in the absence of diarrhea. Furthermore, Anti-lipase IgY treatment restored body weight gain to levels similar to mice fed with Control IgY.
Conclusions
This study provides the first report of the development of anti-lipase IgY and the direct evidence that inhibition of pancreatic lipase using Anti-lipase IgY is an effective anti-obesity treatment due to the associated increase in fecal excretion of triglyceride.
doi:10.1186/1743-7075-10-70
PMCID: PMC4028892  PMID: 24321125
Obesity; IgY; Pancreatic lipase; Lipid; Mice
4.  Dohaekseunggi-tang extract inhibits obesity, hyperlipidemia, and hypertension in high-fat diet-induced obese mice 
Background
Dohaekseunggi-tang (DHSGT) is a traditional plant-based medicine prescribed to promote blood circulation and to treat obesity and hypertension. The present study aimed to identify potential anti-obesity activities of DHSGT extract.
Methods
Anti-obesity, anti-hyperlipidemic, and anti-hypertensive effects of orally-administered DHSGT extract were evaluated in high-fat diet- (HFD)-induced obese mice. Serum biochemistry profiles and expression of diverse metabolic regulatory gene mRNAs in mouse visceral fat were assessed by RT-PCR. The effects of DHSGT on angiotensin-1 converting enzyme (ACE) and pancreatic lipase activities were determined using in vitro inhibition assays.
Results
Oral DHSGT treatment reduced obese HFD C57BL/6 J mouse body weight, liver and adipose tissue mass, adipocyte size, and blood pressure versus untreated HFD mice. DHSGT also decreased serum total cholesterol, LDL-cholesterol, triglyceride, glucose, and leptin concentrations, and increased HDL-cholesterol and adiponectin levels in HFD mice. Furthermore, DHSGT markedly increased mRNA expression of peroxisome proliferator activated receptor-gamma, uncoupling protein-2, and adiponectin in visceral adipose tissue of HFD mice. In vitro tests revealed that DHSGT effectively inhibited porcine pancreatic lipase and ACE activities, with IC50 values of 7.58 mg/ml and 0.56 mg/ml, respectively.
Conclusions
These results validate traditional knowledge and suggest that DHSGT may be potentially useful for managing hyperlipidemia, hyperglycemia, hypertension, and obesity.
doi:10.1186/1472-6882-14-372
PMCID: PMC4193160  PMID: 25280587
Angiotensin-1 converting enzyme; Body weight; Dohaekseunggi-tang; High-fat diet; Pancreatic lipase; Visceral adipose tissue
5.  Antiobesity effect of Stellaria media against drug induced obesity in Swiss albino mice 
Ayu  2011;32(4):576-584.
The whole plant of Stellaria media (family: Caryophyllaceae) has been tested for its antiobesity activity by using progesterone-induced obesity model in female albino mice. The effect of S. media on food consumption pattern, change in body weight, thermogenesis, lipid metabolism, and histology of fat pad. were examined. Methanolic and alcoholic extracts of the S. media were used in the study. Methanolic extract of S. media (MESM) have prevented the increase in body weight, adipose tissue weight and size, and upturned obesity and associated complications. MESM has also shown promising effects compared with alcoholic extract of S. media may be because of its multiple mechanisms. These findings suggest that antiobesity activity produced by MESM is because of its anorexic property mediated by saponin and flavonoid and partly of by its β-sitosterol content. β-Sitosterol in the plant extract was confirmed by thin-layer chromatography study. β-sitosterol is plant sterol having structural similarity with dietary fat which do the physical competition in the gastrointestinal tract and reduces fat absorption. Before carrying in vivo activity detail pharmacognostic and phytochemical analysis of the extracts was carried out. The plant has shown the presence of saponin, flavonoids, steroids and triterpenoids, glycosides, and anthocynidine. By this study, it can be concluded that, MESM is beneficial in suppression of obesity induced by progesterone.
doi:10.4103/0974-8520.96137
PMCID: PMC3361939  PMID: 22661858
Anorexia; histology of fat pads; obesity; progesterone; Stellaria media; β-sitosterol
6.  Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats 
AIM: To investigate the effect of Platycodon grandi-florum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats.
METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis.
RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE significantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue.
CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet. From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.
doi:10.3748/wjg.v13.i25.3493
PMCID: PMC4146786  PMID: 17659697
Obesity; High fat diet; Platycodon grandi-florum extract; Fatty acid binding protein; Subcutaneous adipose tissue
7.  Effects of Fortunella margarita Fruit Extract on Metabolic Disorders in High-Fat Diet-Induced Obese C57BL/6 Mice 
PLoS ONE  2014;9(4):e93510.
Introduction
Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice.
Methods
The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay.
Results
In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes.
Conclusion
Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.
doi:10.1371/journal.pone.0093510
PMCID: PMC3976270  PMID: 24705395
8.  Biochemical and histological impact of Vernonia amygdalina supplemented diet in obese rats 
This study was carried out to evaluate the anti-obesity effect of Vernonia amygdalina Del. (VA) supplemented diet. VA leaf powder was fed at 5% and 15% to diet-induced obese rats for 4 weeks and its effect compared with orlistat (5.14 mg/kg p.o.), an anti-obesity drug. Food intake, body and organ weights, total body fat, some lipid components and amino transaminase activities in serum, hepatocytes and brain; as well as serum glucose, were measured during or at end of the study. Result showed respective decrease of 12.78% and 38.51% in body weight gain, of VA fed rats against 17.45% of orlistat at end of study (P < 0.05); but with no effect on food intake. Total body fat was lowered by 28.04% and 30.02% vs. obese control rats (CDC) (P < 0.05). Furthermore, serum triacylglycerol (TG), serum and brain total cholesterol (TCHOL), were down regulated at 15% VA supplementation (P < 0.05). Serum glucose which increased in obese rats by 46.26% (P < 0.05) vs. NC, indicating intolerance, was restored by VA (38.75% and 34.65%) and orlistat (31.80%) vs. CDC (P < 0.05). VA diet also exerted hepato-protection, via lowering serum alanine amino transaminase (ALT) (41.35% and 27.13%) and aspartate amino transaminase (AST) (17.09% and 43.21%) activities (P < 0.05). Orlistat had no effect on these enzymes. Histology of adipose tissue corroborated the changes on total body fat. We concluded that, diet supplemented with VA can attenuate dietary obesity as well as ameliorates the potential risks of hepato-toxicity and glucose intolerance associated with obesity.
doi:10.1016/j.sjbs.2012.05.003
PMCID: PMC3730893  PMID: 23961200
Vernonia amygdalina Del.; Adipose tissue; Histology; Total body fat; Lipid profile; Glucose intolerance; Diet-induced obesity
9.  Carboxyl Ester Lipase Deficiency Exacerbates Dietary Lipid Absorption Abnormalities and Resistance to Diet-induced Obesity in Pancreatic Triglyceride Lipase Knockout Mice* 
The Journal of biological chemistry  2007;282(34):24642-24649.
This study evaluated the contributions of carboxyl ester lipase (CEL) and pancreatic triglyceride lipase (PTL) in lipid nutrient absorption. Results showed PTL deficiency has minimal effect on triacylglycerol (TAG) absorption under low fat dietary conditions. Interestingly, PTL−/− mice displayed significantly reduced TAG absorption compared with wild type mice under high fat/high cholesterol dietary conditions (80.1 ± 3.7 versus 91.5 ± 0.7%, p < 0.05). Net TAG absorption was reduced further to 61.1 ± 3.8% in mice lacking both PTL and CEL. Cholesterol absorption was 41% lower in PTL−/− mice compared with control mice (p < 0.05), but this difference was not exaggerated in PTL−/−,CEL−/− mice. Retinyl palmitate absorption was reduced by 45 and 60% in PTL−/− mice (p < 0.05) and PTL−/−,CEL−/− mice (p < 0.01), respectively. After 15 weeks of feeding, the high fat/high cholesterol diet, wild type, and CEL−/− mice gained ∼24 g of body weight. However, body weight gain was 6.2 and 8.6 g less (p < 0.01) in PTL−/− and PTL−/−,CEL−/− mice, respectively, despite their consumption of comparable amounts of the high fat/high cholesterol diet. The decrease body weight gain in PTL−/− and PTL−/−,CEL−/− mice was attributed to their absorption of fewer calories from the high fat/high cholesterol diet, thereby resulting in less fat mass accumulation than that observed in wild type and CEL−/− mice. Thus, this study documents that PTL and CEL serve complementary functions, working together to mediate the absorption of a major portion of dietary fat and fat-soluble vitamin esters. The reduced lipid absorption efficiency due to PTL and CEL inactivation also resulted in protection against diet-induced obesity.
doi:10.1074/jbc.M702530200
PMCID: PMC2045644  PMID: 17604277
10.  Liver Fatty Acid Binding Protein Gene-Ablated Female Mice Exhibit Increased Age-Dependent Obesity123 
The Journal of nutrition  2008;138(10):1859-1865.
Previous work done in our laboratory suggested a role for liver fatty acid binding protein (L-FABP) in obesity that develops in aging female L-FABP gene-ablated (−/−) mice. To examine this possibility in more detail, cohorts of wild-type (+/+) and L-FABP (−/−) female mice were fed a standard low-fat nonpurified rodent diet for up to 18 mo. Various obesity-related parameters were examined including body weight and fat and lean tissue mass. Obesity in (−/−) mice was associated with increased expression of nuclear receptors that induce peroxisome proliferator-activated receptor α (PPARα) (e.g., hepatocyte nuclear factor 1α, genotype effectα and of PPARα-regulated proteins involved in uptake of free (lipoprotein lipase and fatty acid transport protein, genotype and/or age effect) and esterified (scavenger receptor class B type 1, genotype effect) long chain fatty acids (LCFAs). Hepatic total lipid and neutral lipid levels were not affected by age or genotype, consistent with absence of gross and histologic steatosis. There was increased mRNA expression of liver proteins involved in LCFA oxidation [mitochondrial 3-oxoacyl-CoA thiolase (genotype effect) and butyryl-CoA dehydrogenase (genotype and/or age effect)], increased expression of LCFA esterification enzymes [glycerol-3-phosphate acyltransferase (age × genotype effect) and acyl-CoA:cholesterol acyltransferase-2 (genotype and/or age effect)], and increased expression of proteins involved in intracellular transfer and secretion of esterified LCFA [liver microsomal triacylglycerol transfer protein (genotype effect), serum apolipoprotein B (genotype or age effect), and liver apolipoprotein B (age and age × genotype effect)]. The data support a working model in which obesity development in these mice results from shifts toward reduced energy expenditure and/or more efficient energy uptake in the gut.
PMCID: PMC2835297  PMID: 18806093
11.  Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation 
Genes & Nutrition  2013;9(1):361.
Quercetin exhibits a wide range of biological functions. The first aim of the present work was to analyze the effects of quercetin on fat accumulation in adipose tissue and glycemic control in rats. Any potential involvement of muscle fatty acid oxidation in its effect on glycemic control was also assessed. Animals were fed a high-fat high-sucrose diet either supplemented with quercetin (30 mg/kg body weight/day), or not supplemented, for 6 weeks. One week before killing, a glucose tolerance test was carried out. Muscle triacylglycerol content, serum glucose, insulin, fructosamine and free fatty acids were measured, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. The activities of lipogenic enzymes and lipoprotein lipase in adipose tissue, carnitine palmitoyl transferase-1b (CPT-1b) and citrate synthase in skeletal muscle, and the expression of several genes, ACO, CD36, CPT-1b, PPAR-α, PGC-1α, UCP3, TFAM and COX-2 in skeletal muscle were analyzed. Quercetin caused no significant reduction in body weight or adipose tissue sizes. However, fructosamine, basal glucose and insulin, and consequently HOMA-IR, were significantly reduced by quercetin. No changes were observed in the activity of lipogenic enzymes and lipoprotein lipase. Muscle triacylglycerol content was similar in both experimental groups. The expression of ACO, CD36, CPT-1b, PPAR-α, PGC-1α, UCP3, TFAM and COX-2 remained unchanged. It can be concluded that quercetin is more effective as an anti-diabetic than as an anti-obesity biomolecule. The improvement in insulin resistance induced by this flavonoid is not mediated by a delipidating effect in skeletal muscle.
doi:10.1007/s12263-013-0361-7
PMCID: PMC3896623  PMID: 24338341
Quercetin; Glycemic control; Fat accumulation; Adipose tissue; Muscle; Fatty acid oxidation; Rat
12.  OA01.38. Anti-obesity activity of Zizyphyus mauritiana lam: a potent pancreatic lipase inhibitor 
Ancient Science of Life  2012;32(Suppl 1):S38.
Purpose:
To study anti-obesity activity of Ziziphus mauritiana Lam bark powder (ZMBP) on High Fat Diet (HFD) induced obesity in rats.
Method:
Obesity was induced in Wistar rats by feeding high fat diet (HFD) for 70 days. The obese rats were distributed in 4 groups (n=5). Group 1: Normal (lean) Control, Group 2: Obese Control, Group 3: Obese rats administered orally 250 mg/kg ZMBP daily, Group 4: Obese rats dosed with 500 mg/kg ZMBP daily, Group 5: Obese rats dosed with Standard Drug Sibutramine, 0.90 mg/kg. The rats were dosed orally daily for a period of 90 days. The animals were screened for induction of obesity by analysing obesity parameters such as Body weight, Anthropological Parameters, Serum Tryglycerides, Serum Cholesterol, Glucose tolerance test, Insulin resistance Test, DEXA analysis and MRI Scan.
Result:
At the end of 90 days treatment with ZMBP the obese rats showed 16.33 % reduction in body weight gain at 250 mg/kg and 17.38 % (P<0.05) reduction in body weight gain at 500 mg/kg when compared with the obese control group respectively. The standard drug Sibutramine showed 5.52% reduction in body weight gain when compared with the obese control group. The DEXA analysis at the end of 90 days of treatment showed 68.99 % (P<0.01) decrease in the Fat mass at 250 mg/kg dose and 72.84 % (P<0.001) decrease in the Fat mass at 500 mg/kg dose when compared with the obese control group. The pancreatic lipase activity in 250mg/kg (5.13+0.71 U/mg of protein) and in 500 mg/kg (4.01+0.86 I/mg of protein) reduced significantly (P<0.001) when compared with the obese control group (9.73+2.39 U/mg of protein)
Conclusion:
The ZMBP has anti-obesity activity at 250 mg/kg and 500-mg/kg dose. It has lipase inhibitory activity.
PMCID: PMC3800916
13.  Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats 
Background
Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats.
Methods
In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3.
Results
No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration.
Conclusions
These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.
doi:10.1186/1476-511X-9-77
PMCID: PMC2918615  PMID: 20653972
14.  Partial Inhibition of Adipose Tissue Lipolysis Improves Glucose Metabolism and Insulin Sensitivity Without Alteration of Fat Mass 
PLoS Biology  2013;11(2):e1001485.
Partial inhibition of adipose tissue lipolysis does not increase fat mass but improves glucose metabolism and insulin sensitivity through modulation of fatty acid turnover and induction of fat cell de novo lipogenesis.
When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet–fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.
Author Summary
In periods of energy demand, mobilization of fat stores in mammals (i.e., adipose tissue lipolysis) is essential to provide energy in the form of fatty acids. In excess, however, fatty acids induce resistance to the action of insulin, which serves to regulate glucose metabolism in skeletal muscle and liver. Insulin resistance (or low insulin sensitivity) is believed to be a cornerstone of the complications of obesity such as type 2 diabetes and cardiovascular diseases. In this study, our clinical observation of natural variation in fat cell lipolysis in individuals reveals that a high lipolytic rate is associated with low insulin sensitivity. Furthermore, partial genetic and pharmacologic inhibition of hormone-sensitive lipase, one of the enzymes involved in the breakdown of white adipose tissue lipids, results in improvement of insulin sensitivity in mice without gain in body weight and fat mass. We undertake a series of mechanistic studies in mice and in human fat cells to show that blunted lipolytic capacity increases the synthesis of new fatty acids from glucose in fat cells, a pathway that has recently been shown by others to be a major determinant of whole body insulin sensitivity. In conclusion, partial inhibition of adipose tissue lipolysis is a plausible strategy in the treatment of obesity-related insulin resistance.
doi:10.1371/journal.pbio.1001485
PMCID: PMC3576369  PMID: 23431266
15.  Extracts of Pomelo Peels Prevent High-Fat Diet-Induced Metabolic Disorders in C57BL/6 Mice through Activating the PPARα and GLUT4 Pathway 
PLoS ONE  2013;8(10):e77915.
Objective
Metabolic syndrome is a serious health problem in both developed and developing countries. The present study investigated the anti-metabolic disorder effects of different pomelo varieties on obese C57BL/6 mice induced by high-fat (HF) diet.
Design
The peels of four pomelo varieties were extracted with ethanol and the total phenols and flavonoids content of these extracts were measured. For the animal experiment, the female C57BL/6 mice were fed with a Chow diet or a HF diet alone or supplemented with 1% (w/w) different pomelo peel extracts for 8 weeks. Body weight and food intake were measured every other day. At the end of the treatment, the fasting blood glucose, glucose tolerance and insulin (INS) tolerance test, serum lipid profile and insulin levels, and liver lipid contents were analyzed. The gene expression analysis was performed with a quantitative real-time PCR assay.
Result
The present study showed that the Citrus grandis liangpinyou (LP) and beibeiyou (BB) extracts were more potent in anti-metabolic disorder effects than the duanshiyou (DS) and wubuyou (WB) extracts. Both LP and BB extracts blocked the body weight gain, lowered fasting blood glucose, serum TC, liver lipid levels, and improved glucose tolerance and insulin resistance, and lowered serum insulin levels in HF diet-fed mice. Compared with the HF group, LP and BB peel extracts increased the mRNA expression of PPARα and its target genes, such as FAS, PGC-1α and PGC-1β, and GLUT4 in the liver and white adipocyte tissue (WAT).
Conclusion
We found that that pomelo peel extracts could prevent high-fat diet-induced metabolic disorders in C57BL/6 mice through the activation of the PPARα and GLUT4 signaling. Our results indicate that pomelo peels could be used as a dietary therapy and the potential source of drug for metabolic disorders.
doi:10.1371/journal.pone.0077915
PMCID: PMC3797771  PMID: 24147098
16.  Syzygium aromaticum ethanol extract reduces high-fat diet-induced obesity in mice through downregulation of adipogenic and lipogenic gene expression 
Numerous medicinal plants and their derivatives have been reported to prevent obesity and related diseases. Although Syzygium aromaticum has traditionally been used as an anodyne, carminative and anthelmintic in Asian countries, its potential in the prevention and treatment of obesity has not yet been explored. Therefore, the present study investigated the anti-obesity effect of S. aromaticum ethanol extract (SAE) both in vitro and in vivo. To evaluate the anti-obesity potential of SAE in vitro, the effect of SAE treatment on adipocyte differentiation in 3T3-L1 cells was investigated. To evaluate its potential in vivo, mice were assigned to three groups: a group fed the American Institute of Nutrition AIN-76A diet (normal group), an experimental group fed a high-fat diet (HFD group) and an experimental group fed an HFD supplemented with 0.5% (w/w) SAE (HFD + SAE group). After 9 weeks of feeding, the body weight; white adipose tissue (WAT) mass; serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, glucose, insulin and leptin; hepatic lipid accumulation; and levels of lipid metabolism-related genes in the liver and WAT were measured. In vitro investigation of the effect of SAE treatment on 3T3-L1 cells revealed that it had efficiently inhibited the conversion of cells into adipocytes in a dose-dependent manner. In vivo investigation revealed that SAE supplementation had significantly decreased HFD-induced increases in the body weight, liver weight, WAT mass, and serum TG, TC, lipid, glucose, insulin and leptin levels. Consistent with its effects on liver weight and WAT mass, SAE supplementation was found to have suppressed the expression of lipid metabolism-related proteins, including SREBP-1, FAS, CD36 and PPARγ in the liver and WAT, in addition to downregulating mRNA levels of transcription factors including Srebp and Pparg. SAE inhibits fat accumulation in HFD-fed mice via the suppression of transcription factors integral to adipogenesis and lipogenesis, suggesting its potential in preventing obesity.
doi:10.3892/etm.2012.609
PMCID: PMC3503535  PMID: 23181109
obesity; lipogenesis adipogenesis; Syzygium aromaticum
17.  Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice 
Background
Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice.
Methods and results
Eight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p<0.001). Inflammation measured by mRNA expressions of IL-6, MMP-9, PAI-1 and leptin and protein expression of NF-κB was higher, whereas anti-inflammation measured by mRNA expressions of adiponectin and INF-γ was lower in obesity than in control and OR (all p<0.003). Oxidative protein expressions of NOX-1, NOX-2 and oxidized protein were higher, whereas expression of anti-oxidant markers HO-1 and NQO-1 were lower (all p<0.01); and apoptosis measured by Bax and caspase 3 was higher, whereas anti-apoptotic Bcl-2 was lower in obesity as compared with control and OR (all p<0.001). The expressions of fibrotic markers phosphorylated Smad3 and TGF-β were higher, whereas expression of anti-fibrotic phosphorylated Smad1/5 and BMP-2 were lower (all p<0.02); and LVEF was lower, whereas the LV remodeling was higher in obesity than in control and OR (all p<0.001).
Conclusion
Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.
doi:10.1186/1479-5876-10-145
PMCID: PMC3551744  PMID: 22784636
Obesity; Inflammation; Oxidative stress; Apoptosis; Fibrosis
18.  HOX-7 suppresses body weight gain and adipogenesis-related gene expression in high-fat-diet-induced obese mice 
Background
HOX-7 is a newly developed dietary formula composed of traditional oriental herbal medicines. The formula was developed with the aim of improving weight control. We investigated the anti-obesity effect of HOX-7 on high-fat-diet (HFD)-induced obesity in C57BL/6 mice.
Methods
The mice were divided into four groups and were fed a normal diet (ND), HFD, or HFD with oral administration of HOX-7 at 100 or 200 mg/kg/day for 12 weeks. Body and fat weight, histological changes of fat tissue, and the expression of key adipogenic transcription factors were investigated.
Results
The body weight of mice fed the HFD with HOX-7 was significantly decreased compared to the HFD group. There were no obvious differences in weekly food intake among the 4 groups. The weight of the epididymal and total fat pads was reduced in mice fed the HFD with HOX-7. Treatment with HOX-7 also substantially attenuated the expression of key adipogenic transcription factors, including peroxisome proliferatoractivated receptor γ, CCAAT/enhancer binding protein α, sterol regulatory element binding protein 1c, adipocyte P2, liver X receptor, and lipoprotein lipase in the epididymal adipose tissue.
Conclusion
Overall, this study highlighted the anti-obesity effects of HOX-7, a finding that could contribute to the development of natural anti-obesity herbal medicines.
doi:10.1186/1472-6882-14-505
PMCID: PMC4320579  PMID: 25515293
C/EBPα; Mice; Obesity; PPARγ; SREBP1c; Traditional herbal medicine
19.  Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model 
Laboratory Animal Research  2012;28(1):31-38.
Overweight and obesity are usually related with high fat and calorie intake, and seriously causative of lifestyle-related diseases such as cardiovascular disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel dietary therapy against overweight and obesity using mixtures of protamine and chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in the body. Protamine is a dietary protein originated from salmon reproductive organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS strongly suppressed the activity of pancreatic lipase, which is the primary enzyme for the digestion and absorption of lipids in the intestine. In in vivo animal test, the mixtures of protamine and COS significantly reduced the serum levels of triglyceride (TG), total cholesterol (T-CHO), and low density lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they increased fecal TG and T-CHO contents. From these alterations in lipid metabolism, we verified that protamine and COS mixtures could effectively interrupt the digestion and absorption of dietary lipids in the body by inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures increased the serum level of high density lipoprotein-cholesterol (HDLC), responsible for removing cholesterol from cells and protecting atherosclerosis, and therefore decreased the potential risks of cardiovascular diseases by lowering values of the atherogenic index (AI) and cardiac risk factor (CRF). Taken together, we suggest protamine and COS mixtures as a prominent dietary therapy for the prevention of overweight, obesity, and further cardiovascular diseases related with hyperlipidemia.
doi:10.5625/lar.2012.28.1.31
PMCID: PMC3315200  PMID: 22474472
Protamine; chitooligosaccharide; high fat diet; triglyceride; cholesterol
20.  Lifetime Medical Costs of Obesity: Prevention No Cure for Increasing Health Expenditure 
PLoS Medicine  2008;5(2):e29.
Background
Obesity is a major cause of morbidity and mortality and is associated with high medical expenditures. It has been suggested that obesity prevention could result in cost savings. The objective of this study was to estimate the annual and lifetime medical costs attributable to obesity, to compare those to similar costs attributable to smoking, and to discuss the implications for prevention.
Methods and Findings
With a simulation model, lifetime health-care costs were estimated for a cohort of obese people aged 20 y at baseline. To assess the impact of obesity, comparisons were made with similar cohorts of smokers and “healthy-living” persons (defined as nonsmokers with a body mass index between 18.5 and 25). Except for relative risk values, all input parameters of the simulation model were based on data from The Netherlands. In sensitivity analyses the effects of epidemiologic parameters and cost definitions were assessed. Until age 56 y, annual health expenditure was highest for obese people. At older ages, smokers incurred higher costs. Because of differences in life expectancy, however, lifetime health expenditure was highest among healthy-living people and lowest for smokers. Obese individuals held an intermediate position. Alternative values of epidemiologic parameters and cost definitions did not alter these conclusions.
Conclusions
Although effective obesity prevention leads to a decrease in costs of obesity-related diseases, this decrease is offset by cost increases due to diseases unrelated to obesity in life-years gained. Obesity prevention may be an important and cost-effective way of improving public health, but it is not a cure for increasing health expenditures.
Using a simulation model, Pieter van Baal and colleagues conclude that obesity prevention leads to a decrease in costs of obesity-related diseases, but this is offset by cost increases due to diseases unrelated to obesity in life-years gained.
Editors' Summary
Background.
Since the mid 1970s, the proportion of people who are obese (people who have an unhealthy amount of body fat) has increased sharply in many countries. One-third of all US adults, for example, are now classified as obese, and recent forecasts suggest that by 2025 half of US adults will be obese. A person is overweight if their body mass index (BMI, calculated by dividing their weight in kilograms by their height in meters squared) is between 25 and 30, and obese if BMI is greater than 30. Compared to people with a healthy weight (a BMI between 18.5 and 25), overweight and obese individuals have an increased risk of developing many diseases, such as diabetes, coronary heart disease and stroke, and tend to die younger. People become unhealthily fat by consuming food and drink that contains more energy than they need for their daily activities. In these circumstances, the body converts the excess energy into fat for use at a later date. Obesity can be prevented, therefore, by having a healthy diet and exercising regularly.
Why Was This Study Done?
Because obesity causes so much illness and premature death, many governments have public-health policies that aim to prevent obesity. Clearly, the improvement in health associated with the prevention of obesity is a worthwhile goal in itself but the prevention of obesity might also reduce national spending on medical care. It would do this, the argument goes, by reducing the amount of money spent on treating the diseases for which obesity is a risk factor. However, some experts have suggested that these short-term savings might be offset by spending on treating the diseases that would occur during the extra lifespan experienced by non-obese individuals. In this study, therefore, the researchers have used a computer model to calculate yearly and lifetime medical costs associated with obesity in The Netherlands.
What Did the Researchers Do and Find?
The researchers used their model to estimate the number of surviving individuals and the occurrence of various diseases for three hypothetical groups of men and women, examining data from the age of 20 until the time when the model predicted that everyone had died. The “obese” group consisted of never-smoking people with a BMI of more than 30; the “healthy-living” group consisted of never-smoking people with a healthy weight; the “smoking” group consisted of lifetime smokers with a healthy weight. Data from the Netherlands on the costs of illness were fed into the model to calculate the yearly and lifetime health-care costs of all three groups. The model predicted that until the age of 56, yearly health costs were highest for obese people and lowest for healthy-living people. At older ages, the highest yearly costs were incurred by the smoking group. However, because of differences in life expectancy (life expectancy at age 20 was 5 years less for the obese group, and 8 years less for the smoking group, compared to the healthy-living group), total lifetime health spending was greatest for the healthy-living people, lowest for the smokers, and intermediate for the obese people.
What Do These Findings Mean?
As with all mathematical models such as this, the accuracy of these findings depend on how well the model reflects real life and the data fed into it. In this case, the model does not take into account varying degrees of obesity, which are likely to affect lifetime health-care costs, nor indirect costs of obesity such as reduced productivity. Nevertheless, these findings suggest that although effective obesity prevention reduces the costs of obesity-related diseases, this reduction is offset by the increased costs of diseases unrelated to obesity that occur during the extra years of life gained by slimming down.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0050029.
The MedlinePlus encyclopedia has a page on obesity (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of obesity (in English and Spanish)
The UK National Health Service's health Web site (NHS Direct) provides information about obesity
The International Obesity Taskforce provides information about preventing obesity
The UK Foods Standards Agency, the United States Department of Agriculture, and Shaping America's Health all provide useful advice about healthy eating
The Netherlands National Institute for Public Health and the Environment (RIVM) Web site provides more information on the cost of illness and illness prevention in the Netherlands (in English and Dutch)
doi:10.1371/journal.pmed.0050029
PMCID: PMC2225430  PMID: 18254654
21.  Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract 
Background
This study was undertaken to provide pharmacological basis for the medicinal use of Viola odorata Linn. in hypertension and dyslipidemia using the in vivo and in vitro assays.
Results
Viola odorata leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 μM) and K+ (80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca++ concentration-response curves as well as suppression of PE (1 μM) control peaks in Ca++-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C.
Conclusions
These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca++ influx via membranous Ca++ channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of Viola odorata in hypertension and dyslipidemia.
doi:10.1186/1476-511X-11-6
PMCID: PMC3286389  PMID: 22233644
Viola odorata leaves; antihypertensive; antidyslipidemic; Ca++ antagonist; NO-mediated.
22.  Anti-obesity activity of chloroform-methanol extract of Premna integrifolia in mice fed with cafeteria diet 
Aim of the study:
Aim of the present study was to evaluate the anti-obesity activity of chloroform:methanol extract of P. integrifolia (CMPI) in mice fed with cafeteria diet.
Materials and Methods:
Female Swiss Albino mice were divided into six groups, which received normal and cafeteria diet, standard drug simvastatin (10 mg/kg) and CMPI (50, 100 and 200 mg/kg) daily for 40 days. Parameters such as body weight, body mass index (BMI), Lee index of obesity (LIO), food consumption, locomotor behavior, serum glucose, triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index, organ weight and organ fat pad weight were studied for evaluating the anti-obesity activity of P. integrifolia. High performance liquid chromatography (HPLC) fingerprint profile of chloroform-methanol extract was also studied using quercetin as the reference standard.
Results:
There was a significant increase in body weight, BMI, LIO, food consumption, organ weight (liver and small intestine), organ fat pad weight (mesenteric and peri-renal fat pad) and in the levels of serum glucose, triglyceride, total cholesterol, LDL and VLDL with a significant decrease in locomotor behavior (ambulation, rearing, grooming) and HDL level in cafeteria diet group. Animals treated with CMPI showed dose dependent activity. P. integrifolia (200 mg/kg) supplementation attenuated all the above alterations, which indicates the anti-obesity activity. HPLC fingerprint profile of CMPI showed two peaks in the solvent system of 50 mm potassium diphosphate (pH-3 with ortho phosphoric acid): Methanol (30:70 v/v) at 360 nm.
Conclusion:
Present findings suggest that, CMPI possessed anti-obesity activity that substantiated its ethno-medicinal use in the treatment of obesity.
doi:10.4103/0975-7406.116825
PMCID: PMC3778593  PMID: 24082700
Cafeteria diet; chloroform-methanol extract (1:1); obesity; Premna integrifolia
23.  Whole-Body Vibration Training Effect on Physical Performance and Obesity in Mice 
The purpose of this study was to verify the beneficial effects of whole-body vibration (WBV) training on exercise performance, physical fatigue and obesity in mice with obesity induced by a high-fat diet (HFD). Male C57BL/6 mice were randomly divided into two groups: normal group (n=6), fed standard diet (control), and experimental group (n=18), fed a HFD. After 4-week induction, followed by 6-week WBV of 5 days per week, the 18 obese mice were divided into 3 groups (n=6 per group): HFD with sedentary control (HFD), HFD with WBV at relatively low-intensity (5.6 Hz, 0.13 g) (HFD+VL) or high-intensity (13 Hz, 0.68 g) (HFD+VH). A trend analysis revealed that WBV increased the grip strength in mice. WBV also dose-dependently decreased serum lactate, ammonia and CK levels and increased glucose level after the swimming test. WBV slightly decreased final body weight and dose-dependently decreased weights of epididymal, retroperitoneal and perirenal fat pads and fasting serum levels of alanine aminotransferase, CK, glucose, total cholesterol and triacylglycerol. Therefore, WBV could improve exercise performance and fatigue and prevent fat accumulation and obesity-associated biochemical alterations in obese mice. It may be an effective intervention for health promotion and prevention of HFD-induced obesity.
doi:10.7150/ijms.9975
PMCID: PMC4196122  PMID: 25317067
vibration training; exercise performance; fatigue; obesity; high fat diet
24.  Weight loss herbal intervention therapy (W-LHIT) a non-appetite suppressing natural product controls weight and lowers cholesterol and glucose levels in a murine model 
Background
The prevalence of obesity is increasing in industrialized countries. Obesity increases the risk of coronary artery disease, stroke, cancer, hypertension, and type-2 diabetes. Unfortunately, conventional obesity drug treatment is often associated with adverse effects. The objective of this study was to evaluate a novel natural formula, Weight loss herbal intervention therapy (W-LHIT), developed from traditional Chinese medicine, for weight control in a high-fat-diet (HFD) induced obesity murine model.
Methods
Two sets of experiments were performed. In experiment 1, 14-week-old C57BL/6 J male mice were fed with HFD for 21days and then separated into 3 weight-matched groups. One group continued on the HFD as obese-controls. Two groups were switched from HFD to normal fat level diet (NFD) and sham or W-LHIT treated. In experiment 2, 25-week-old obese mice, following 2weeks acclimatization, received either W-LHIT or sham treatment while maintained on HFD. In both sets of experiments, NFD fed, age matched normal weight mice served as normal controls. Body weight and food intake were recorded. Epididymal fat pad weight, serum glucose and cholesterol levels, as well as PPARγ and FABP4 gene expression in epididymal fat tissue were analyzed at the end of the experiment.
Results
In experiment 1, W-LHIT treated obese mice lost body weight 12.2 ± 3.8% whereas sham treated mice lost 5.5 ± 2.8% by day 10 after switching from the HFD to the NFD, without reduction of chow consumption. In experiment 2, W-LHIT treated obese mice maintained on the HFD had significantly lower body weight (8 fold less) than the sham treated mice. W-LHIT treatment also reduced epididymal fat pad weight, blood cholesterol and glucose levels versus sham treated mice without reduced chow consumption. In addition, significantly increased PPARγ (peroxisome proliferator activated receptor γ) and FABP4 (fatty acid binding protein 4) gene expression were found in epdidymal fat tissues. Liver and kidney function and hematology testing results of W-LHIT treated mice were within the normal range.
Conclusions
W-LHIT significantly and safely reduced body weight, normalized glucose and cholesterol levels in obese mice, without suppression of appetite, and increased adipocyte PPARγ and FABP4 gene expression.
doi:10.1186/1472-6882-14-261
PMCID: PMC4125697  PMID: 25055851
Obesity; C57BL/6 J; High fat diet; W-LHIT natural product; Weight loss; Serum glucose; Cholesterol; PPARγ
25.  Effects of prolonged ethanol intake and malnutrition on rat pancreas. 
Gut  1996;38(2):285-292.
Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.
Images
PMCID: PMC1383039  PMID: 8801213

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