The prevalence of obesity has increased dramatically. A direct comparison in the predisposition to obesity between males, premenopausal females, and postmenopausal females with various caloric intakes has not been made. To determine the effects of sex and ovarian hormones on the susceptibility to obesity, we conducted laboratory studies with mice. To eliminate confounders that can alter body weight gain, such as age and food consumption; we used mice with the same age and controlled the amount of calories they consumed.
We determined sex-specific susceptibility to obesity between male, non-ovariectomized female, and ovariectomized female mice. To compare susceptibility to gaining body weight between males and females, animals from each sex were exposed to either a 30% calorie-restricted, low-fat (5% fat), or high-fat (35% fat) diet regimen. To establish the role of ovarian hormones in weight gain, the ovaries were surgically removed from additional female mice, and then were exposed to the diets described above. Percent body fat and percent lean mass in the mice were determined by dual energy x-ray absorptiometry (DEXA).
In all three diet categories, male mice had a greater propensity of gaining body weight than female mice. However, ovariectomy eliminated the protection of female mice to gaining weight; in fact, ovariectomized female mice mimicked male mice in their susceptibility to weight gain. In summary, results show that male mice are more likely to become obese than female mice and that the protection against obesity in female mice is eliminated by ovariectomy.
Understanding metabolic differences between males and females may allow the discovery of better preventive and treatment strategies for diseases associated with body weight such as cancer and cardiovascular disease.
Intrauterine growth retardation due to maternal under-nutrition increases susceptibility to obesity and insulin resistance. We reported earlier in the offspring of mineral or vitamin restricted rat dams, a high body fat percentage and decreased insulin secretion to glucose challenge. This study determined whether or not central adiposity and altered adipocytokine profile were associated with high body fat content.
Body fat percentage; glucose, insulin and adipocytokine levels in fasting plasma and fresh weights of epididymal fat pads were determined in the six months old male offspring of Wistar NIN rat dams on chronic 50 percent restriction of vitamins or minerals throughout their growth, gestation, lactation and weaned on to restricted diets or restricted mothers/offspring rehabilitated from different time points.
In line with high body fat percent, chronic restriction of vitamins and minerals increased the epididymal fat pad weight. Maternal vitamin restriction decreased plasma adiponectin and increased leptin levels whereas mineral restriction decreased both. Both the treatments did not affect plasma TNF-α levels or insulin resistance status (HOMA-IR). Rehabilitation from parturition but not weaning, rescued the changes in the offspring.
High body fat percentage in the offspring of vitamin restricted or mineral restricted rat dams was associated with increased abdominal adiposity (epididymal fat pad weight) and differential expression of adipocytokines but not insulin resistance. The changes could be mitigated by rehabilitation from birth but not weaning.
Given the increasing concerns about the levels of obesity being reached throughout the world, this paper analyses the relationship between the most common index of obesity, the BMI, and levels of body fat.
Research methods and procedures
The statistical relationship, in terms of functional form, between body fat and BMI is analysed using a large data set which can be categorized by race, sex and age.
Irrespective of race, body fat and BMI are linearly related for males, with age entering logarithmically and with a positive effect on body fat. Caucasian males have higher body fat irrespective of age, but African American males’ body fat increases with age faster than that of Asians and Hispanics. Age is not a significant predictor of body fat for females, where the relationship between body fat and BMI is nonlinear except for Asians. Caucasian females have higher predicted body fat than other races, except at low BMIs, where Asian females are predicted to have the highest body fat.
Using BMIs to make predictions about body fat should be done with caution, as such predictions will depend upon race, sex and age and can be relatively imprecise. The results are of practical importance for informing the current debate on whether standard BMI cut-off values for overweight and obesity should apply to all sex and racial groups given that these BMI values are shown to correspond to different levels of adiposity in different groups.
obesity; functional form; prediction; gender; race
Guberan, E. and Fernandez, J. (1974).British Journal of Industrial Medicine,31, 159-167. Control of industrial exposure to tetrachloroethylene by measuring alveolar concentrations: theoretical approach using a mathematical model. The uptake, distribution, and elimination of tetrachloroethylene were studied using a mathematical model, and predicted alveolar concentrations were compared with experimental data. Because of its high fat solubility the solvent accumulated in adipose tissue with a predicted biological half-life of 71·5 hours. The relation between the alveolar concentrations and the level or duration of exposure was discussed. The alveolar concentrations of tetrachloroethylene during and after similar exposure were predicted in subjects who differed in age, body weight, height, and body fat content, both at rest and during physical effort. Predictions were made of the alveolar concentrations following exposures to steady and variable concentrations in ambient air, and following exposures of several weeks of the type occuring in industry. It was concluded that measurement of the postexposure alveolar concentrations could be used to estimate the mean exposure to tetrachloroethylene in most industrial situations.
Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. Our objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Values for parameters such as alveolar ventilation, cardiac output, organ volumes, blood flow, partition coefficients, and metabolic rate constants were taken from the literature. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a mumole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Model simulations for PHC and PMA, generally considered to be detoxification metabolites, were similar in shape and dose-response to those for total metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, and mammary gland of Sprague-Dawley rats following chronic oral administration of benzene. The cause for the specificity of such lesions remains unclear, but it is possible that tissue-specific metabolism or pharmacokinetics of benzene is responsible. Metabolism and pharmacokinetic studies were carried out in our laboratory with 14C-benzene at oral doses of 0.15 to 500 mg/kg to ascertain tissue retention, metabolite profile, and elimination kinetics in target and nontarget organs and in blood. Findings from those studies indicate the following: a) the Zymbal gland is not a sink or a site of accumulation for benzene or its metabolites even after a single high dose (500 mg/kg) or after repeated oral administration; b) the metabolite profile is quantitatively different in target tissues (e.g., Zymbal gland, nasal cavity), nontarget tissues and blood; and (c) pharmacokinetic studies show that the elimination of radioactivity from the Zymbal gland is biphasic.
An early-life adverse environment has been implicated in the susceptibility to different diseases in adulthood, such as mental disorders, diabetes and obesity. We analyzed the effects of a high-fat sucrose (HFS) diet for 35 days in adult female rats that had experienced 180 minutes daily of maternal separation (MS) during lactancy. Changes in the obesity phenotype, biochemical profile, levels of glucocorticoid metabolism biomarkers, and the expression of different obesity- and glucocorticoid-metabolism-related genes were analyzed in periovaric adipose tissue. HFS intake increased body weight, adiposity and serum leptin levels, whereas MS decreased fat pad masses but only in rats fed an HFS diet. MS reduced insulin resistance markers but only in chow-fed rats. Corticosterone and estradiol serum levels did not change in this experimental model. A multiple gene expression analysis revealed that the expression of adiponutrin (Adpn) was increased owing to MS, and an interaction between HFS diet intake and MS was observed in the mRNA levels of leptin (Lep) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). These results revealed that early-life stress affects the response to an HFS diet later in life, and that this response can lead to phenotype and transcriptomic changes.
High-fat (HF) diet feeding usually leads to hyperphagia and body weight gain, but macronutrient proportions in the diet can modulate energy intake and fat deposition. The mechanisms of fat accumulation and mobilization may differ significantly between depots, and gender can also influence these differences.
To investigate, in rats of both sexes, the effect of an isocaloric intake of a diet with an unbalanced proportion of macronutrients on fatty acid composition of visceral and subcutaneous adipose tissues and how this is influenced by both dietary fatty acids and levels of proteins involved in tissue lipid handling.
Eight-week-old Wistar rats of both sexes were fed a control diet (3% w/w fat) or high-fat diet (30% w/w fat) for 14 weeks. Fatty acid composition was analyzed by gas-chromatography and levels of LPL, HSL, α2-AR, β3-AR, PKA and CPT1 were determined by Western blot.
The HF diet did not induce hyperphagia or body weight gain, but promoted an increase of adiposity index only in male rats. HF diet produced an increase of the proportion of MUFA and a decrease in that of PUFA in both adipose depots and in both sexes. The levels of proteins involved in the adrenergic control of the lipolytic pathway increased in the gonadal fat of HF females, whereas LPL levels increased in the inguinal fat of HF males and decreased in that of females.
Sexual dimorphism in adiposity index reflects a differential sex response to dietary fatty acid content and could be related to the levels of the proteins involved in tissue lipid management.
The production of an experimental uremia in the albino rat by removal of both kidneys is followed by hypertrophy of the adrenal glands. In the case of male rats 90 days of age this adrenal enlargement amounted to 65 per cent and in the case of female rats 180 days of age 47 per cent. The increase in the size of the whole gland is due entirely to hypertrophy of the cortex. This increase in the volume of cortical tissue amounted to approximately 40 per cent for males and 61 per cent for females and was due in large part to an increase in the size of the cells. The content of water and material soluble in fat solvents was higher in the uremic than the control glands. However after subtraction of such storage materials a true hypertrophy of the cortex still remained. It amounted to 21 per cent. Histologically the stainable fat had a more irregular distribution and was present in lesser amount in the adrenals from the uremic animals. The capillaries of the medulla and reticular cortex were distended. The nuclei of both the cortical and medullary cells were swollen and stained faintly.
Apart from the well known inhibitory effects of estradiol on food intake, meal size, and body weight in female rats that have been documented over the past thirty years, a more recent report presents the opposite finding; that a large dose of estradiol can increase food intake and weight gain in gonadally intact female rats presented with a palatable diet. The purpose of the present experiment was to further examine this hypothesis by evaluating the ability of estradiol to influence feeding behavior in ovariectomized rats presented with diets that differ in flavor and fat content. Female rats were given a cyclic regimen of estradiol benzoate treatment (5.0 or 20.0 µg) or the oil vehicle and were presented with the standard chow diet or a diet with a higher fat content and chocolate flavor. Food intake, meal size, and meal number were monitored three days after the first injection of estradiol or oil. Compared to the chow diet, food intake increased when animals had access to the chocolate/fat diet during the vehicle treatment condition. Both doses of estradiol significantly decreased food intake, meal size, and body weight gain when animals were presented with either the standard chow diet or the chocolate/fat diet. These findings indicate that estradiol does not stimulate the intake of a palatable diet in ovariectomized rats, and suggest that previous results showing that estradiol enhanced eating and weight gain stemmed from a disruption of the hypothalamic-pituitary-gonadal axis when intact females received a large dose of exogenous estradiol.
estradiol; palatable food; meal size; body weight
Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.
specific cross sectional reference values for lung function indices
usually employ a linear model with terms for age and stature. The
effects of also matching for body mass index (BMI= mass/stature2) or its components, fat percentage of body
mass (fat%) and fat free mass index (FFMI = fat free
mass/stature2) were studied.
were 458 asymptomatic male and female non-smokers (383 men) and 22 female ex-smokers. Measurements were made of ventilatory capacity, lung
volumes, transfer factor (diffusing capacity, single breath CO method),
and body composition (skinfold method). Linear and proportional
regression models were used.
fat% and FFMI significantly improved the accuracy of reference values
for all the primary lung function indices. The improvements in subjects
with atypical physiques (fat% and FFMI at the ends of the
distributions for the subjects) were in the range 0.3-2.3 SD compared
with conventional regression equations. The new partial regression
coefficients on age were independent of age related changes in body
fat. The coefficient for total lung capacity (TLC) on age in men was
now positive. Most differences between the sexes were eliminated. A
term for BMI improved the descriptions of subdivisions of TLC but
lacked the other advantages.
for fat% and FFMI increases the accuracy of reference equations for
lung function, particularly for subjects with a lot of fat and little
muscle or vice versa. Allowance for BMI is less informative.
The Zymbal gland, a sebaceous tissue associated with the ear duct of certain rodent species, is a principal target for carcinogenesis by benzene. To investigate the mechanism of induction of tumors in the rat Zymbal gland, we have developed a procedure for primary culture of epithelial cells from Zymbal gland explants so that cytogenetic analysis can be performed on this target tissue following an in vivo exposure to benzene. Cytogenetic analysis performed 45 hr after in vivo oral dosing with benzene revealed chromosome damage that occurred as a result of acute, subchronic, and chronic dosing. This damage, expressed as a dose-related increase in the frequency of micronucleated cells, was observed in Sprague-Dawley female rats over a range of benzene doses from 12.5 to 250 mg/kg/day, and in male Fischer 344 rats at doses ranging from 1 to 200 mg/kg/day. These results are consistent with the known clastogenicity of benzene in mouse bone marrow, which is also a target tissue. This study is the first report of a genotoxic effect of benzene in the rat Zymbal gland and shows that micronucleus formation may be used as a correlate for carcinogenesis induced by benzene in this target tissue.
A description has been given of the pathologic changes produced experimentally in animals by the inoculation of a virus material obtained from a mouse with spontaneous encephalomyelitis. The most distinctive feature of the lesions in the central nervous system is the widespread destruction of myelin. Giant cells derived from a variety of tissue elements characterize the early lesions. The liver in the majority of cases is the seat of focal necrosis. In some mice, infected with large doses by the intravenous route, there is produced massive necrosis of the liver, with fat infiltration and calcification. Giant cells are occasionally found in lymphatic tissue, but no significant changes were noted in other organs. Inclusions or elementary bodies were not demonstrated in the lesions. Similar lesions were produced by the inoculation of mouse virus into hamsters. In rats, the lesions were of a more chronic character. The relation of this disease to other demyelinating diseases of man and animals is discussed.
Ten male volunteers were exposed to ethylene glycol monoethyl ether acetate (EGEE-Ac) under various conditions of exposure and physical workload. As exposure proceeded, retention, atmospheric clearance, and uptake rate declined slowly to reach steady state levels after three to four hours. Retention increased as a consequence of higher exposure concentrations and of physical workload performed during exposure. Uptake rate was higher as exposure concentration or pulmonary ventilation rate, or both, increased. Subject related factors such as pulmonary ventilation, cardiac output, height, and body fat content also determined individual uptake. During exposure, partial respiratory elimination of EGEE was observed. This finding confirms the hypothesis that EGEE-Ac is first converted to EGEE by (plasma) esterases. The amount of EGEE eliminated at steady state levels correlated more with uptake rate of EGEE-Ac than with exposure concentration. Respiratory elimination of unmetabolised EGEE-Ac accounted for less than or equal to 0.5% of total body uptake. The elimination curves were biexponential indicating that at least two pharmacological compartments are involved. Postexposure breath concentrations were higher as total body uptake increased. Several observations may indicate that the hydrolysis of the ester moiety of EGEE-Ac is hindered by the presence of the natural esterase substrates. With increasing plasma concentrations, however, EGEE-Ac competed more favourably for the available esterase.
At a given external dose of an inhaled chemical the internal dose or the amount absorbed into the body varies depending on pulmonary ventilation and other physiological factors. Such variability is of concern in the development of biological indices of occupational exposure to organic solvent vapours. This paper discusses how physiological factors may influence the pharmacokinetic behaviour of inhaled organic solvent vapours, especially in relation to monitoring of biological exposure. To illustrate the discussion a computer based physiological pharmacokinetic model was used describing quantitatively the influence of body size, body fat content, and sex on the pharmacokinetic behaviour of trichloroethylene. Absorption, distribution, metabolism and excretion of trichloroethylene were found to vary according to the different anatomical features of men and women. Body build (body weight and body fat content) also affected the pharmacokinetic behaviour of this solvent.
Variations in the fatty acid composition of lipids in the heart alter its function and susceptibility to ischaemic injury. We investigated the effect of sex and dietary fat intake on the fatty acid composition of phospholipids and triacylglycerol in rat heart. Rats were fed either 40 or 100 g/kg fat (9:1 lard:soybean oil) from weaning until day 105. There were significant interactive effects of sex and fat intake on the proportions of fatty acids in heart phospholipids, dependent on phospholipid classes. 20:4n-6, but not 22:6n-3, was higher in phospholipids in females than males fed a low, but not a high, fat diet. There was no effect of sex on the composition of triacylglycerol. These findings suggest that sex is an important factor in determining the incorporation of dietary fatty acids into cardiac lipids. This may have implications for sex differences in susceptibility to heart disease.
Heart; Fatty acids; Phophospholipids; Triacylglycerol; Sex; Rat
Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F1 mice, and female B6C3F1 mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS)
Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH.
Background & Aims
Steatosis in patients with nonalcoholic fatty liver disease (NAFLD) is due to an imbalance between intrahepatic triglyceride (IHTG) production and export. The purpose of this study was to evaluate TG metabolism in adipose tissue and liver in NAFLD.
Fatty acid, VLDL-TG, and VLDL-apolipoprotein B-100 (apoB100) kinetics were assessed by using stable isotope tracers in 14 nondiabetic obese subjects with NAFLD (IHTG, 22.7% ± 2.0%) and 14 nondiabetic obese subjects with normal IHTG content (IHTG, 3.4% ± 0.4%), matched on age, sex, body mass index, and percent body fat.
Compared with the normal IHTG group, the NAFLD group had greater rates of palmitate release from adipose tissue into plasma (85.4 ± 6.6 and 114.1 ± 8.1 µmol/min, respectively; P = .01) and VLDL-TG secretion (11.4 ± 1.1 and 24.3 ± 3.1 µmol/min, respectively; P = .001); VLDL-apoB100 secretion rates were not different between groups. The increase in VLDL-TG secretion was primarily due to an increased contribution from “nonsystemic” fatty acids, presumably derived from lipolysis of intrahepatic and intra-abdominal fat and de novo lipogenesis. VLDL-TG secretion rate increased linearly with increasing IHTG content in subjects with normal IHTG but reached a plateau when IHTG content was ≥10% (r = 0.618, P < .001).
Obese persons with NAFLD have marked alterations in both adipose tissue (increased lipolytic rates) and hepatic (increased VLDL-TG secretion) TG metabolism. Fatty acids derived from nonsystemic sources are responsible for the increase in VLDL-TG secretion. However, the increase in hepatic TG export is not adequate to normalize IHTG content.
Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.
Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.
In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.
These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.
Early dietary exposure can influence susceptibility to obesity and type 2 diabetes later in life. We examined the lasting effects of a high protein or high prebiotic fiber weaning diet when followed by a high energy diet in adulthood.
At birth, litters of Wistar rats were culled to 10 pups. At 21 d pups were weaned onto control (C), high prebiotic fiber (HF) or high protein (HP) diet. Rats consumed the experimental diets until 14 wk when they were switched to a high fat/sucrose (HFHS) diet for 6 wk. Body composition and energy intake were measured and an oral glucose tolerance test (OGTT) performed. Blood was analyzed for satiety hormones and tissues collected for real-time PCR.
Weight gain was attenuated in male rats fed HF from 12 wk until study completion. In females there were early reductions in body weight that moderated until the final two wk of HFHS diet wherein HF females weighed less than HP. Final body weight was significantly higher following the high fat challenge in male and female rats that consumed HP diet from weaning compared to HF. Lean mass was higher and fat mass lower with HF compared to HP and compared to C in males. Energy intake was highest in HP rats, particularly at the start of HFHS feeding. Plasma glucose was higher in HP rats compared to HF during an OGTT. Plasma amylin was higher in HF females compared to C and glucagon-like peptide-1 (GLP-1) was higher in HF rats during the OGTT. Leptin was higher in HP rats during the OGTT. HF upregulated GLUT 5 mRNA expression in the intestine and downregulated hepatic hydroxymethylglutaryl coenzyme A reductase. Male rats fed HP had higher hepatic triglyceride content than C or HF.
These data suggest that while a long-term diet high in protein predisposes to an obese phenotype when rats are given a high energy diet in adulthood, consumption of a high fiber diet during growth may provide some protection.
Previous studies have illustrated the importance of leptin receptor (OB-Rb) mediated action on adipocytes in the regulation of body weight. The aim of the present study was to investigate in male and female rats the effects of high-fat (HF) diet feeding on the expression levels of OB-Rb in different depots of white adipose tissue (WAT), and its relation to fatty acid oxidation capacity. Male and female Wistar rats were fed until the age of 6 months with a normal-fat (NF) or non-isocaloric HF-diet (10 and 45% calories from fat, respectively). At this age, the weight of three different fat depots (retroperitoneal, mesenteric and inguinal) and the expression levels of OB-Rb, PPARα and CPT1 in these depots were measured. HF-diet feeding resulted in an increase in the weight of the different fat depots, the retroperitoneal depot being the one with the greatest increase in both sexes. In this depot, HF-diet feeding resulted in a significant decrease in OB-Rb mRNA levels, more marked in male than in female rats. In the mesenteric depot, the effects of HF-diet feeding on OB-Rb mRNA levels were sex-dependent: they decreased in males rats (associated with a decrease in PPARα and CPT1 mRNA levels), but increased in female rats. In the inguinal depot, OB-Rb expression was not affected by HF-diet feeding. These results show that a chronic intake of an HF-diet altered the expression of OB-Rb in WAT in a depot and sex-dependent manner. The decreased expression of OB-Rb in the internal depots of male rats under HF-diet feeding, with the resulting decrease in leptin sensitivity, can help to explain the higher tendency of males to suffer from obesity-linked disorders under HF-diet conditions.
High-fat diet; Leptin; OB-Rb; Sex-dimorphism; White adipose tissue depots
It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD.
Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 ± 2 kg/m2; intrahepatic triglyceride (IHTG) ≤5.5% of liver volume) and increased (n = 9; BMI = 36 ± 2 kg/m2; IHTG ≥ 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic-euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free-fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content.
The rate of whole-body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 ± 7 vs. 127 ± 13 μmol/min; P < 0.01) and during physiological hyperinsulinemia, (24 ± 2 vs. 44 ± 8 μmol/min; P < 0.01).
These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.
Quantitative trait loci (QTL) affecting fatness in male chickens were previously identified on chromosome 5 (GGA5) in a three-generation design derived from two experimental chicken lines divergently selected for abdominal fat weight. A new design, established from the same pure lines, produced 407 F2 progenies (males and females) from 4 F1-sire families. Body weight and abdominal fat were measured on the F2 at 9 wk of age. In each sire family, selective genotyping was carried out for 48 extreme individuals for abdominal fat using seven microsatellite markers from GGA5. QTL analyses confirmed the presence of QTL for fatness on GGA5 and identified a QTL by sex interaction. By crossing one F1 sire heterozygous at the QTL with lean line dams, three recombinant backcross 1 (BC1) males were produced and their QTL genotypes were assessed in backcross 2 (BC2) progenies. These results confirmed the QTL by sex interaction identified in the F2 generation and they allow mapping of the female QTL to less than 8 Mb at the distal part of the GGA5. They also indicate that fat QTL alleles were segregating in both fat and lean lines.
meat-type chickens; quantitative trait loci; fatness QTL; QTL × sex interaction