Health benefits of Kochujang (KCJ) and its bioactive compounds have been reported in several in vitro and animal studies.
The aim of this study was to investigate the efficacy of KCJ supplementation on body composition and blood lipid profiles in overweight adults.
Sixty overweight men and women with BMI ≥23 kg/m2 and waist-hip-ratio (WHR) ≥0.90 for men and ≥0.85 for women were randomly assigned to a KCJ supplement (n=30, 32 g/day) or placebo (n=30, 32 g/day) group for a 12-week, double-blind, placebo controlled study. We measured anthropometric parameters, serum lipid profiles, abdominal fat distribution by computerized tomography and calculated the atherosclerosis indices in 53 subjects (n=26 in KCJ group, n=27 in placebo group) who completed the study.
After 12 weeks, the KCJ group showed a significant reduction in visceral fat (cm2) (p<0.05), although body weight (kg) and WHR did not change. Serum concentration of triglycerides and ApoB were decreased when compared to those of the placebo group.
KCJ supplementation (32 g/day) for 12 weeks in overweight adults showed anti-atherosclerotic and anti-obesogenic effects.
Clinical trials.gov Identifier:
Kochujang (KCJ); Visceral fat; Triglyceride; Atherosclerosis index; Apolipoprotein
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Dietary intake of n-3 polyunsaturated fatty acids (PUFA) is primarily recognized to protect against cardiovascular diseases, cognitive dysfunctions and the onset of obesity and associated metabolic disorders. However, some of their properties such as bioavailability can depend on their chemical carriers. The objective of our study was to test the hypothesis that the nature of n-3 PUFA carrier results in different metabolic effects related to adiposity, oxidative stress and inflammation.
4 groups of C57BL/6 mice were fed for 8 weeks low fat (LF) diet or high-fat (HF, 20%) diets. Two groups of high-fat diets were supplemented with long-chain n-3 PUFA either incorporated in the form of phospholipids (HF-ω3PL) or triacylglycerols (HF-ω3TG).
Both HF-ω3PL and HF-ω3TG diets reduced the plasma concentrations of (i) inflammatory markers such as monocyte chemoattractant protein-1 (MCP-1) and interleukin 6 (IL-6), (ii) leptin and (iii) 4-hydroxy-2-nonenal (4-HNE), a marker of n-6 PUFA-derived oxidative stress compared with the control HF diet. Moreover, in both HF-ω3PL and HF-ω3TG groups, MCP-1 and IL-6 gene expressions were decreased in epididymal adipose tissue and the mRNA level of gastrointestinal glutathione peroxidase GPx2, an antioxidant enzyme, was decreased in the jejunum compared with the control HF diet. The type of n-3 PUFA carrier affected other outcomes. The phospholipid form of n-3 PUFA increased the level of tocopherols in epididymal adipose tissue compared with HF-ω3TG and resulted in smaller adipocytes than the two others HF groups. Adipocytes in the HF-ω3PL and LF groups were similar in size distribution.
Supplementation of mice diet with long-chain n-3 PUFA during long-term consumption of high-fat diets had the same lowering effects on inflammation regardless of triacyglycerol or phospholipid carrier, whereas the location of these fatty acids on a PL carrier had a major effect on decreasing the size of adipocytes that was not observed with the triacyglycerol carrier. Altogether, these results would support the development functional foods containing LC n-3 PUFA in the form of PL in order to prevent some deleterious outcomes associated with the development of obesity.
n-3 PUFA; Phospholipid; Triacylglycerol; High-fat diet; Inflammation; Oxidative stress; Adipose tissue
Dietary strategies seem to be the most prescribed therapy in order to counteract obesity regarding not only calorie restriction, but also bioactive ingredients and the composition of the consumed foods. Dietary total antioxidant capacity (TAC) is gaining importance in order to assess the quality of the diet.
Ninety-six obese adults presenting metabolic syndrome (MetS) symptoms completed an 8-week intervention trial to evaluate the effects of a novel dietary program with changes in the nutrient distribution and meal frequency and to compare it with a dietary pattern based on the American Heart Association (AHA) guidelines.
Anthropometric and biochemical parameters were assessed at baseline and at the endpoint of the study, in addition to 48-hours food dietary records.
Both diets equally (p > 0.05) improved MetS manifestations. Dietary TAC was the component which showed the major influence on body weight (p = 0.034), body mass index (p = 0.026), waist circumference (p = 0.083) and fat mass (p = 0.015) reductions. Transaminases (ALT and AST) levels (p = 0.062 and p = 0.004, respectively) were associated with lower TAC values.
RESMENA diet was as effective as AHA pattern for reducing MetS features. Dietary TAC was the most contributing factor involved in body weight and obesity related markers reduction.
Antioxidant; Weight loss; Energy restriction; Macronutrient distribution; Dietary components; Nutritional profile
Obesity and related morbidities are reaching epidemic proportions in the Arab populations. Possible mechanisms that link obesity/visceral fat to diabetes and cardiovascular (CVD) complications include inflammation and increased oxidative stress. The aim of this study is to test whether supplementary antioxidants with B-group vitamins enhance antioxidant capacity and/or mitigate oxidative damage and subclinical inflammation in obese diabetic patients.
Hundred diabetic patients were randomly assigned to receive either oral dose of daily B-group vitamins (1.67 mg folic acid, 1.67 mg vitamin B-2, 20 mg vitamin B-6, 0.134 mg vitamin B-12) and antioxidant vitamins (221 mg of α-tocopherol and 167 mg of vitamin C) [n = 50], or an identical placebo [n = 50] daily for 90 days. Blood was obtained before treatment, and after 90 days for measurements of plasma antioxidant vitamins status, markers of oxidative damage [malondialdehyde (MDA) and protein carbonyls] and inflammation (C-Reactive Proteins [CRP], IL6 & TNFα).
Supplementation with antioxidant and B-group vitamins increased plasma concentration of vitamin E and folate and reduced homocysteine in the intervention groups compared with the placebo group. Vitamin B12 improved in the supplement group compared with the decline seen in the placebo group however, this did not reach statistical significance. Vitamin C declined in both groups but more so in the intervention group. Both MDA and Protein carbonyls increased in both the supplement and the placebo group. IL6 concentration increased in both groups but less so in the supplement group (p = 0.023). TNF showed more pronounced decline in the supplement group compared with the placebo group but the difference between cumulative changes did not reach statistical significance (p = 0.204). CRP concentrations declined in the supplement group in contrast to the rise seen in the placebo group however, the difference between cumulative changes was not statistically significant (p = 0.205).
Antioxidants supplementation with B-group vitamins enhances antioxidant capacity, and may have an anti-inflammatory effect in obese diabetic patients.
Diabetes; Obesity; Inflammation; Antioxidants; Oxidative damage
This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-γ), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-α) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.
Hepatic injury-markers; Melatonin; Folic acid; Akt1; Oxidative stress; Anti-inflammatory effects
Phenolic compounds combine antioxidant and hypocholesterolemic activities and, consequently, are expected to prevent or minimize cardiometabolic risk.
To evaluate the effect of an aqueous extract (AQ) and non-esterified phenolic fraction (NEPF) from rosemary on oxidative stress in diet-induced hypercholesterolemia, 48 male 4-week old Wistar rats were divided into 6 groups: 1 chow diet group (C) and 5 hypercholesterolemic diet groups, with 1 receiving water (HC), 2 receiving AQ at concentrations of 7 and 140 mg/kg body weight (AQ70 and AQ140, respectively), and 2 receiving NEPF at concentrations of 7 and 14 mg/kg body weight (NEPF7 and NEPF14, respectively) by gavage for 4 weeks.
In vitro, both AQ and NEPF had remarkable antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH●) assay, which was similar to BHT. In vivo, the group that received AQ at 70 mg/kg body weight had lower serum total cholesterol (−39.8%), non-HDL-c (−44.4%) and thiobarbituric acid reactive substance (TBARS) levels (−37.7%) compared with the HC group. NEPF (7 and 14 mg/kg) reduced the tissue TBARS levels and increased the activity of tissular antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). Neither AQ nor NEPF was able to ameliorate the alterations in the hypercholesterolemic diet-induced fatty acid composition in the liver.
These data suggest that phenolic compounds from rosemary ameliorate the antioxidant defense in different tissues and attenuate oxidative stress in diet-induced hypercholesterolemic rats, whereas the serum lipid profile was improved only in rats that received the aqueous extract.
Hypercholesterolemia; Oxidative stress; Polyphenols; Rosmarinus officinalis
Patients with inflammatory bowel disease (IBD) frequently appear iron deplete but whether this is a reflection of dietary iron intakes is not known.
Dietary data were collected from 29 patients with inactive or mildly-active IBD and 28 healthy controls using a validated food frequency questionnaire that measured intakes of iron and its absorption modifiers. Non-haem iron availability was estimated using a recently developed algorithm. Subjects were classified for iron status based upon data from a concomitant and separately published study of iron absorption. Absorption was used to define iron status because haematological parameters are flawed in assessing iron status in inflammatory conditions such as IBD.
Dietary intakes of total iron, non-haem iron and vitamin C were significantly greater in IBD patients who were iron replete compared to those who were iron deplete (by 48%, 48% and 94% respectively; p≤0.05). The predicted percentage of available non-haem iron did not differ between these groups (19.7 ± 2.0% vs 19.3 ± 2.0% respectively; p=0.25). However, because of the difference in iron intake, the overall amount of absorbed iron did (2.4 ± 0.8 mg/d vs 1.7 ± 0.5 mg/d; p=0.013). No such differences were observed in the healthy control subjects.
In IBD, iron status is more closely related to the quality and quantity of dietary iron intake than in the general healthy population.
IBD; Iron deficiency anaemia; Iron intake; Diet; Food frequency questionnaire
The objective of present study was to examine the effect of long-chain monounsaturated fatty acids (LC-MUFAs) with chain lengths longer than 18 (i.e., C20:1 and C22:1 isomers combined) on obesity-related metabolic dysfunction and its molecular mechanisms. Type-2 diabetic KK-Ay mice (n = 20) were randomly assigned to the 7% soybean oil-diet group (control group) and 4% LC-MUFA concentrate-supplemented-diet group (LC-MUFA group). At 8 weeks on the diet, the results showed that plasma, liver and adipose tissue levels of C20:1 and C22:1 isomers increased significantly with LC-MUFA treatment. Supplementation with LC-MUFAs markedly reduced white fat pad weight as well as adipocyte size in the mice. The levels of plasma free fatty acids, insulin, and leptin concentration in the obese diabetic mice of the LC-MUFA group were also decreased as compared with the mice in the soybean oil-diet control group. Dietary LC-MUFAs significantly increased the mRNA expression of peroxisome proliferator-activated receptor gamma (Pparg), lipoprotein lipase (Lpl), fatty acid transport protein (Fatp), fatty acid translocase/CD36 (Cd36), as well as mRNA expression of genes involved in lipid oxidation such as carnitine palmitoyltransferase-1A (Cpt1a) and citrate synthase (Cs), and decreased the mRNA expression of inflammatory marker serum amyloid A 3 (Saa3) in the adipose tissues of diabetic mice. The results suggest that LC-MUFAs may ameliorate obesity-related metabolic dysfunction partly through increased expression of Pparg as well as its target genes, and decreased inflammatory marker expression in white adipose tissue.
Long-chain monounsaturated fatty acids; Type 2 diabetes mellitus; Pparg; Adipose mass
A blunted muscle protein synthetic response to protein ingestion may contribute to the age related loss of muscle tissue. We hypothesized that the greater endogenous insulin release following co-ingestion of carbohydrate facilitates post-prandial muscle protein accretion after ingesting a meal-like bolus of protein in older males.
Twenty-four healthy older men (75±1 y) were randomly assigned to ingest 20 g intrinsically L-[1-13C] phenylalanine-labeled casein protein with (PRO-CHO) or without (PRO) 40 g carbohydrate. Ingestion of specifically produced intrinsically L-[1-13C] phenylalanine labeled protein allowed us to assess post-prandial incorporation of dietary protein derived amino acids into muscle protein. Blood samples were collected at regular intervals, with muscle biopsies being obtained prior to and 2 and 6 h after protein ingestion.
Plasma glucose and insulin concentrations showed a greater increase in PRO-CHO compared with PRO (P<0.001). Muscle protein-bound L-[1-13C] phenylalanine enrichments tended to increase to a greater extent in PRO-CHO compared with PRO during the first 2 h after protein ingestion (0.0072±0.0013 vs 0.0046±0.010 MPE, respectively; P=0.13). However, 6 h after protein ingestion, differences in muscle protein-bound L-[1-13C] phenylalanine enrichments were no longer observed between experiments (0.0213±0.0024 vs 0.0185±0.0010 MPE, respectively; P=0.30).
This study shows that carbohydrate ingestion may accelerate, but does not further augment post-prandial incorporation of dietary protein derived amino acids into muscle protein in healthy elderly men.
Skeletal muscle; Ageing; Sarcopenia; Amino acids; Anabolic resistance
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The article entitled “Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population”, concluded that higher amounts of individual’s MSG consumption are associated with the risk of having the metabolic syndrome and being overweight independent of other major determinants. However, this epidemiological study is the only study indicating such a relationship between MSG intake and the prevalence of metabolic syndrome and there is no direct supporting evidence for a causal relationship between MSG intake and prevalence of metabolic syndrome. This study does not indicate that MSG causes metabolic syndrome. Furthermore, there are several questionable points concerning study methods. Further carefully designed studies taking into account all glutamate sources are necessary to demonstrate the relationship between overweight, metabolic syndrome, MSG intake and umami sensitivity.
Monosodium glutamate; Intake; Overweight; Metabolic syndrome
Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP) enzymes.
An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day) for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions.
Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity.
Orally added butyrate in bolus could cause in vivo hyperacetylation of the hepatic core histones, providing modifications in the epigenetic regulation of cell function. However, these changes did not result in alteration of drug-metabolizing hepatic CYP2H and CYP3A37 enzymes, so there might be no relevant pharmacoepigenetic influences of oral application of butyrate under physiological conditions.
Short chain fatty acids; Butyrate; Histone deacetylase inhibitor; Histone hyperacetylation; Epigenetics; Cytochrome P450 enzymes
See related article: http://www.nutritionandmetabolism.com/content/10/1/14
GPR43 is a G-protein-coupled receptor that participates in adipocyte differentiation in mice and is over-expressed in adipose tissue of obese mice. The aim of this study was to investigate the implication of GPR43 in adipogenesis in humans and to determine the influence of obesity on its expression in human adipose tissue.
Preadipocytes were isolated from human omental adipose tissue and cultured during 13 days. One PPARγ agonist (troglitazone) and three GPR43 agonists (two physiological and one synthetic) were tested for their ability to induce differentiation. After 13 days, the three GPR43 agonists had no impact on aP2 expression, a marker of adipocyte differentiation, whereas troglitazone led to a huge over-expression of aP2 in these cells but tended to decrease GPR43 expression (p=0.06).
GPR43 and inflammatory markers expression was also quantified in omental adipose tissue from lean and obese individuals. GPR43 expression in total adipose tissue was similar between obese patients and lean subjects and did not correlate with aP2 expression. In contrast, GPR43 expression positively correlated with TNFα mRNA.
Our results suggest the absence of relationship between GPR43 and adipocyte differentiation in humans, unlike what was observed in mice. Furthermore, GPR43 expression is not increased in adipose tissue from obese subjects but could be related to TNFα-related inflammatory processes.
Human; GPR43; Adipocyte differentiation; Obesity; Inflammation
Iron deficiency anaemia and oral iron supplementation have been associated negatively with quality of life, and with adverse effects, respectively, in subjects with inflammatory bowel disease (IBD). Hence, the risk-benefit ratio of oral iron is not understood in this patient group. The present case–control study investigated whether dietary iron intake impacts on quality of life in IBD patients.
Quality of life, habitual dietary iron intakes and iron requirements were assessed in 29 patients with inactive or mildly active IBD as well as in 28 healthy control subjects.
As expected, quality of life was worse in IBD patients as a whole in comparison to healthy controls according to EuroQol score and EuroQol VAS percentage (6.9 ± 1.6 vs 5.3 ± 0.6; p< 0.0001 and 77 ± 14% vs 88 ± 12%; p=0.004 respectively). For IBD subjects, 21/29 were iron deplete based upon serum iron responses to oral iron but, overall, were non-anaemic with mean haemoglobin of 13.3 ± 1.5 g/dL, and there was no difference in their quality of life compared to 8/29 iron replete subjects (Hb 14.0 ± 0.8 g/dL). Interestingly, total dietary iron intake was significantly negatively associated with quality of life in IBD patients, specifically for non-haem iron and, more specifically, for fortificant iron. Moreover, for total non-haem iron the negative association disappeared when fortificant iron values were subtracted. Finally, further sub-analysis indicated that the negative association between (fortificant) dietary iron intake and quality of life in IBD patients is driven by findings in patients with mildly active disease rather than in patients with quiescent disease.
Iron deficiency per se (i.e. without concomitant anaemia) does not appear to further affect quality of life in IBD patients with inactive or mildly active disease. However, in this preliminary study, dietary iron intake, particularly fortificant iron, appears to be significantly negatively associated with quality of life in patients with mildly active disease.
IBD; Iron intake; Iron deficiency; Quality of life; Fortificant iron
See related article: http://www.nutritionandmetabolism.com/content/10/1/14
Monosodium glutamate; Intake; Metabolic syndrome
Metabolic flexibility described as “the capacity of the body to match fuel oxidation to fuel availability” has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM).
We measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95).
The Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p < 0.05) and lower PA levels than Insulin Sensitive (IS) group (P < 0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2 = 0.50, p < 0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p < 0.01), independent of body fat % or distribution.
In these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.
HOMA-IR; Insulin-sensitivity; Dietary fat intake
Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo.
Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-κB and AP-1 in Western blot analysis.
Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-κB p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats.
Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling.
Nephrotoxicity; Nrf2/HO-1 signaling; Melatonin; Oxidative stress
We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.
Intrauterine protein restriction; Postnatal overfeeding; Obesity; Visceral fat; Glucose tolerance
Intestinal derived endotoxin and the subsequent endotoxemia can be considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes. Dietary fat has been shown to increase postprandial endotoxemia. Therefore, the aim of this study was to assess the effects of different dietary oils on intestinal endotoxin transport and postprandial endotoxemia using swine as a model. We hypothesized that oils rich in saturated fatty acids (SFA) would augment, while oils rich in n-3 polyunsaturated fatty acids (PUFA) would attenuate intestinal endotoxin transport and circulating concentrations.
Postprandial endotoxemia was measured in twenty four pigs following a porridge meal made with either water (Control), fish oil (FO), vegetable oil (VO) or coconut oil (CO). Blood was collected at 0, 1, 2, 3 and 5 hours postprandial and measured for endotoxin. Furthermore, ex vivo ileum endotoxin transport was assessed using modified Ussing chambers and intestines were treated with either no oil or 12.5% (v/v) VO, FO, cod liver oil (CLO), CO or olive oil (OO). Ex vivo mucosal to serosal endotoxin transport permeability (Papp) was then measured by the addition of fluorescent labeled-lipopolysaccharide.
Postprandial serum endotoxin concentrations were increased after a meal rich in saturated fatty acids and decreased with higher n-3 PUFA intake. Compared to the no oil control, fish oil and CLO which are rich in n-3 fatty acids reduced ex vivo endotoxin Papp by 50% (P < 0.05). Contrarily, saturated fatty acids increased the Papp by 60% (P = 0.008). Olive and vegetable oils did not alter intestinal endotoxin Papp.
Overall, these results indicate that saturated and n-3 PUFA differentially regulate intestinal epithelial endotoxin transport. This may be associated with fatty acid regulation of intestinal membrane lipid raft mediated permeability.
Dietary fat; Endotoxin; Intestine
Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.
Silicon; Orthosilicic acid; Zeolites; Therapeutic and biological effects
PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters.
We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1).
HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman’s correlations revealed that plasma PCSK9 concentrations upon 7-day HFruc1 diet were positively associated with plasma triglycerides (r=0.54, p=0.01) and IHCL (r=0.56, p=0.001), and inversely correlated with hepatic (r=0.54, p=0.014) and whole-body (r=−0.59, p=0.0065) insulin sensitivity.
Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.
Nutrition; Dietary intervention; PCSK9; Insulin resistance; Liver steatosis
Risk for obesity differs with ethnicity/race and is associated with insulin sensitivity (SI), insulin responsiveness, and dietary glycemic load (GL). The objective of this study was to test the hypotheses that, 1) obesity-prone, normal weight, African-American (AA) women would be more insulin sensitive than BMI-matched, never overweight AA women; 2) increased adiposity over time would be associated with greater baseline SI and higher dietary GL in AA but not European-American (EA) women; and 3) increased adiposity over time would be predicted by SI in women with high but not low acute insulin response to glucose (AIRg).
Two controlled weight loss interventions were conducted involving overweight (BMI 25.0-29.9 kg/m2) premenopausal AA and EA women. The first included matching with normal-weight (BMI <25.0 kg/m2) controls following weight loss, and then comparing SI. The second included a 1-year follow-up of weight-reduced participants to identify predictors of change in %body fat. Main outcome measure in the first study was insulin sensitivity (SI) as assessed with intravenous glucose tolerance test (IVGTT), and in the second study was change in %fat, as assessed with DXA, over one year. AIRg was assessed during IVGTT, and free-living diet was determined by food record.
In the first study, formerly overweight AA women were 43% more insulin sensitive than BMI-matched never overweight AA (P < 0.05). In the second study, SI was positively associated with change in %fat over 1 year only in AA women (P < 0.05) and women with high AIRg (P < 0.05). In addition, AA who were insulin sensitive and who consumed a higher GL diet tended to gain greater %fat (P = 0.086 for diet x SI interaction). In both studies, AA women had higher AIRg (P < 0.001) than EA women.
Formerly overweight (obesity-prone) AA women were more insulin sensitive than never overweight AA women, a quality that may predispose to adiposity, particularly when combined with a high GL diet. This ethnicity/race-specific effect may be due to high insulin responsiveness among AA.
Glycemic index; Diet; Insulin secretion; Acute insulin response
In Lebanon, Type 2 diabetes (T2D) has a major public health impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. Diet is an important environmental factor in the development and prevention of T2D. Dietary patterns may exert greater effects on health than individual foods, nutrients, or food groups. The objective of this study is to examine the association between dietary patterns and the odds of T2D among Lebanese adults.
Fifty-eight recently diagnosed cases of T2D and 116 population-based age, sex, and place of residence matched control participants were interviewed. Data collection included a standard socio-demographic and lifestyle questionnaire. Dietary intake was evaluated by a semi-quantitative 97-item food frequency questionnaire. Anthropometric measurements including weight, height, waist circumference, and percent body fat were also obtained. Dietary patterns were identified by factor analysis. Multivariate logistic regression analysis was used to evaluate the associations of extracted patterns with T2D. Pearson correlations between these patterns and obesity markers, energy, and nutrient intakes were also examined.
Four dietary patterns were identified: Refined Grains & Desserts, Traditional Lebanese, Fast Food and Meat & Alcohol. While scores of the “Refined Grains & Desserts” had the highest correlations with energy (r = 0.74) and carbohydrates (r = 0.22), those of the “Fast Food” had the highest correlation with fat intake (r = 0.34). After adjustment for socio-demographic and lifestyle characteristics, scores of the Refined Grains & Desserts and Fast Food patterns were associated with higher odds of T2D (OR: 3.85, CI: 1.13-11.23 and OR: 2.80, CI: 1.14-5.59; respectively) and scores of the Traditional Lebanese pattern were inversely associated with the odds of T2D (OR: 0.46, CI: 0.22-0.97).
The findings of this study demonstrate direct associations of the Refined Grains & Desserts and Fast Food patterns with T2D and an inverse association between the Traditional Lebanese pattern and the disease among Lebanese adults. These results may guide the development of nutrition interventions for the prevention and management of T2D among Lebanese adults.
Dietary patterns; Lebanon; Type 2 diabetes