Polysiloxane: potential noncaloric fat substitute; effects on body composition of obese Zucker rats

Phenylmethylpolysiloxane (PS), a noncaloric, nonabsorbable liquid oil, was studied for effects on body comparison as fat substitute in the diet. Two groups of female obese Zucker rats were fed either a control low-fat (LF) or an experimental diet containing PS (22% wt/wt) incorporated into LF. Two additional groups were fed either PS or cellulose (CE) in diet providing equivalent caloric dilution. Rats on PS lost weight whereas LF control rats gained. Dissectible fat and adipocyte size of PS were smaller than those of LF. Food intake, body water, and adipocyte number did not differ between PS and LF. Body protein on PS increased only in proportion to weight. When both diets were diluted, PS animals lost more weight than CE controls despite similar food intakes, suggesting absorption of calorigenic substances derived from partial digestion of CE but not PS by intestinal microflora. Obese rats did not compensate for caloric dilution with PS.     

Dietary single cell protein reduces fatty liver in obese Zucker rats

There is growing evidence that dietary proteins may interfere with lipid metabolism. We therefore examined the effects of feeding obese Zucker rats a single cell protein (SCP) with low ratios of methionine:glycine and lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and lowered the plasma transaminase levels when compared with casein-fed rats (controls). The fatty acid oxidation was increased in liver mitochondria and peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG biosynthesis were unaffected. SCP feeding affected the fatty acid composition of liver lipids and plasma, and reduced the mRNA levels of the fatty acid desaturases. The decreased gene expression of stearoyl-CoA desaturase suggested that the fatty acids were directed towards oxidation rather than esterification as TAG. The decreased mRNA levels of VLDL-receptor and lipoprotein lipase in the liver after SCP feeding suggested that the uptake of TAG-rich lipoprotein to the liver was decreased. To conclude, the reduced fatty liver by SCP feeding may be caused by the increased capacity for fatty acid beta-oxidation in the liver, combined with changed fatty acid composition and possibly a reduced hepatic clearance of circulating VLDL. An increased awareness of the effect of dietary proteins on lipid metabolism could be of relevance in future dietary treatment of non-alcoholic fatty liver disease.     

Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats

This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.     

High fat feeding increases brown fat GDP binding in lean but not obese Zucker rats

The effects of high fat feeding on brown fat thermogenesis in rodents are controversial. In this study, we examined the effects of 8 d of high fat feeding on brown fat mitochondrial GDP binding (an in vitro index of thermogenic activity) in lean (Fa/?) and obese (fa/fa) Zucker rats. Six-week-old female rats were fed a defined low fat control diet (9.5% of energy from fat) only during the dark cycle (1200-2400 h), and food intake was measured daily at 1200, 1600, 2300, and 2400 h for 7 d (the control period). For the next 8 d, half of the lean and obese rats were fed a high fat diet (65% of energy from fat), and the others remained on the low fat control diet. Each rat was fed the amount of energy equivalent to its average energy intake during the 7-d control period. Rats were killed at 0800-1000 h. In the lean rats, high fat feeding increased GDP binding. This increased binding in the lean rats appeared to reflect levels of dietary fat and carbohydrate and was independent of caloric intake. The blunted GDP binding of the obese rats failed to respond to dietary changes.     

Dietary conjugated linoleic acid reduces adiposity in lean but not obese Zucker rats

Recent studies have demonstrated a reduction in body fat in growing animals fed conjugated linoleic acid (CLA). Two experiments were conducted to extend these observations to obese rats so that the mechanism of the actions of CLA might be more easily elucidated. In experiment 1, male lean and obese Zucker rats were fed diets containing either 0 or 0.5% CLA for 5 wk. There was no effect of diet on growth rate or food intake. Dietary CLA reduced retroperitoneal and inguinal fat pad weights in the lean rats but increased fat pad weights in the obese genotype (diet x genotype interaction; P < 0.05). Determination of fat pad cellularity indicated that these changes in fat pad weight were due to a reduction or increase in average fat cell size for the lean and obese Zucker rats, respectively. In experiment 2, we sought to reproduce these effects on fat pad size, as well as to determine the effect of dietary CLA on the catabolic response to bacterial endotoxin injection in obese Zucker rats. Growing female lean and obese Zucker rats were fed diets containing 0 or 0.5% CLA for 8 wk. On d 28, each rat was injected intraperitoneally with lipopolysaccharide from Escherichia coli serotype 055:B5 (1 mg/kg body weight) and body weight was determined over the next 96 h. There was a diet x genotype interaction (P < 0.05) for the body weight response to lipopolysaccharide 24 h postinjection. Lean rats fed CLA lost less weight than did lean controls, but obese rats fed CLA lost more weight than did obese controls. As in the first experiment, there was a diet x genotype (P < 0.05) for the effect of treatment on retroperitoneal fat pad weights determined at the end of the experiment. Lean rats fed CLA had smaller RP fat pads than did lean controls, but obese rats fed CLA once again had heavier RP fat pads than did obese controls. These results indicate that CLA reduces body fat and catabolic response to endotoxin injection in lean Zucker rats but not in the obese genotype. The observed interaction between diet and genotype warrants additional investigation into the specific mechanism(s) of the biological activities of CLA.     

The effects of phenylpropanolamine on Zucker rats selected for fat food preference

Treatments of human and rodent obesity frequently involve administration of amphetamine derivatives, much like phenylpropanolamine, which suppress food intake. The Zucker rat is a commonly employed model of youth-onset obesity in which the homozygous genotype manifests hyperphagia as well as other characteristics that parallel human obesity. Using a macronutrient selection procedure, we examined phenylpropanolamine's differential actions in controlling dietary intake, spontaneous open-field activity, and regional hypothalamic neurotransmitter levels in obese female Zucker rats of varying fat food preference. We hypothesized that phenylpropanolamine would alter hypothalamic monoamine levels differently in low-fat preferring and high-fat preferring Zucker rats, and hence affect feeding behavior and activity differently in these two groups. It was found that in high-fat preferring animals, phenylpropanolamine significantly decreased spontaneous open-field activity, decreased only carbohydrate caloric intake, and increased serotonin and 5-HIAA levels in the paraventricular nucleus (PVN). In low-fat preferring animals, phenylpropanolamine decreased carbohydrate, protein, and total caloric intake, had no significant effect of spontaneous activity, and increased serotonin and 5-hydroxyindole acetic acid levels in the PVN. Inherent and induced physiological differences of low-fat and high-fat preferring animals are discussed as well as phenylpropanolamine's potential in combination drug therapy for the treatment of human hyperphagic obesity.     

Rice bran enzymatic extract–supplemented diets modulate adipose tissue inflammation markers in Zucker rats

ObjectiveChronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue and adipokine production deregulation. Obesity also is characterized by oxidative stress related to inflammatory signaling. The aim of this study was to analyze whether dietary supplementation with a rice bran enzymatic extract (RBEE), rich in bioactive compounds with antioxidant and hypocholesterolemic properties, would ameliorate the inflammatory state existing in visceral adipose tissue of obese Zucker rats.MethodsObese Zucker rats and their littermate controls, lean Zucker rats ages 8 wk, were daily fed an enriched diet with either 1% or 5% RBEE supplementation over 20 wk. Measurement of adipocyte size and mRNA expression of proinflammatory molecules from visceral abdominal/epididymal tissue was performed.ResultsAn RBEE-supplemented diet decreased the overproduction of tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and inducible nitric oxide synthase (iNOS), as well as the overproduction of IL-6 and iNOs in visceral abdominal adipose tissue and visceral epididymal adipose tissue, respectively. An RBEE-supplemented diet modified the adipocyte-size distribution pattern in both abdominal and epididymal adipose tissue, shifting it toward smaller cell sizes.ConclusionsChronic administration of a novel water-soluble RBEE, rich in polyphenols, tocotrienols and γ-oryzanol, could be a suitable treatment to ameliorate the obesity-associated proinflammatory response.     

A casein diet added isoflavone-enriched soy protein favorably affects biomarkers of steatohepatitis in obese Zucker rats

ObjectiveDietary supplementation of a soy protein enriched with isoflavones (HDI) has been shown to improve fatty liver in obese rats. The main objective of this study was to investigate whether HDI would influence the inflammatory status in livers of obese rats with fatty liver.MethodsMale obese Zucker fa/fa rats were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk.ResultsThe HDI-fed rats had a markedly lower hepatic concentration of triacylglycerol when compared with controls. The decreased aspartate transaminase/alanine transaminase ratio in plasma, together with lower circulating levels of alkaline phosphatase and bile acids after HDI feeding, implied an improved hepatitis. This was supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor-α, lower plasma levels of interleukin-1β and monocyte chemoattractant protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI also seemed to protect the rats from oxidative damage, because the level of lipid peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation was lower for HDI-fed rats when compared with controls.ConclusionThese results show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy proteins enriched in isoflavones may be a promising agent to improve steatohepatitis in patients.     

Antioxidant effects of a grapeseed procyanidin extract and oleoyl-estrone in obese Zucker rats

ObjectiveTo substantiate the relation between obesity and oxidative stress and to assess the potential beneficial properties of a grapeseed proanthocyanidin extract (GSPE), the amelioration of obesity with oleoyl-estrone (OE), and the possible combined effect of GSPE and OE on the hepatic and renal antioxidant enzyme system in obesity-induced oxidative stress.MethodsMale obese Zucker rats were divided into four groups: GSPE, OE, GSPE + OE, and OC (control). For 30 d they were gavaged with GSPE, OE, GSPE + OE, or sunflower oil as the control vehicle (OC). Lean Zucker rats gavaged with the vehicle comprised the lean control group. Hepatic and renal antioxidant enzymes and oxidative biomarkers were determined at the end of the experimental period.ResultsHepatic antioxidant activities were higher in obese rats than in lean ones. All these activities decreased when obese rats were treated with GSPE, whereas only some of these activities decreased with OE and GSPE + OE treatments. In the kidney, few antioxidant enzymes had higher activities in obese than in lean rats, and OE and GSPE + OE were the treatments that inhibited most enzymes studied. Glutathione S-transferase activity was always lower with the exception of the kidney of obese rats and all treatments used increased the low glutathione levels found in obesity.ConclusionGSPE and OE improve oxidative stress in obese Zucker rats. The effect of GSPE + OE is comparable to GSPE for the liver and to OE for the kidney. Thus the effects of GSPE and OE are not additive and are organ dependent.     

The effects of dietary fat content on the growth and body composition of lean and genetically obese Zucker rats adrenalectomized before weaning

1. Lean (Fa/-) and obese (fa/fa) Zucker rats were adrenalectomized or sham-operated at 18 d of age (3 d before weaning). After weaning the rats were fed ad lib. on semi-synthetic diets containing either a low (8 g/kg) or a high (178 g/kg) proportion of fat. Other groups of sham-operated rats were given the same amount eaten by adrenalectomized animals (restricted intake). Rats were killed at 40 d of age. 2. Adrenalectomy reduced the body lipid content of lean and obese rats compared with intact animals fed ad lib. or given a restricted intake. Adrenalectomized obese rats contained more body lipid than intact or adrenalectomized lean rats. 3. Sham-operated obese rats given a restricted intake had less body protein than similarly treated lean animals and this phenotypic difference was abolished by adrenalectomy. 4. There were no effects of diet on growth or body composition of intact or adrenalectomized rats. 5. It is concluded that preweaning adrenalectomy prevented development of the obese phenotype when rats were fed on either diet. Comparison of these results with a previous study, in which adrenalectomized Zucker rats were fed on a stock diet (Fletcher, 1986b), showed, however, that feeding either of the semi-synthetic diets caused greater deposition of body lipid in obese rats.     

Increased A-ring reduction of glucocorticoids in obese Zucker rats: effects of insulin sensitization

OBJECTIVE: Obesity is associated with altered glucocorticoid metabolism, which may impact on hypothalamic-pituitary-adrenal axis activity. Here we characterize hepatic 5alpha- and 5beta-reductase in obese rats and their responses to insulin sensitization. RESEARCH METHODS AND PROCEDURES: Hepatic A-ring reductase protein and mRNA were assessed in lean and obese Zucker rats after insulin sensitization with metformin or rosiglitazone (n = 7 to 8/group). RESULTS: Hepatic 5alpha-reductase 1 and 5beta-reductase mRNA and protein (p < 0.01) were increased in obese rats. Insulin sensitization ameliorated increased 5alpha-reductase 1 mRNA in obese rats (p < 0.01) and partially reversed increased 5beta-reductase activity. DISCUSSION: Hepatic clearance of glucocorticoids by 5alpha- and 5beta-reductase is increased in obese Zucker rats, and this increase in clearance is attenuated by insulin sensitization. This increased hepatic clearance may underpin compensatory activation of the hypothalamic-pituitary-adrenal axis in obesity.     

Effect of dehydroepiandrosterone on growth in lean and obese Zucker rats

Several studies were undertaken to determine the effect of dehydroepiandrosterone (DHEA) on growth in Zucker rats. In experiment 1, 3 weeks of DHEA treatment in lean rats resulted in decreased body weight gain in comparison to control rats. In experiment 2, both lean and obese rats were treated with DHEA from 6 to 21 weeks of age. Significant decreases in body weight were found for both lean and obese DHEA-treated rats. The food efficiency ratio (FER) was significantly decreased in both DHEA-treated groups. Significant decreases in parametrial and retroperitoneal fat pads were found in both lean and obese DHEA-treated rats. This was primarily attributed to a decrease in fat cell number in lean rats and to decreases in both number and size of fat cells in obese rats. In experiment 3 obese female rats were treated with DHEA from 6 to 21 weeks of age followed by 15 weeks with DHEA removed from the diet. Significantly more weight was gained by the rats previously treated than by the control rats, but body weight remained significantly lower than in the control groups. These data indicate DHEA has an effect on altering body weight and body fat in lean and obese Zucker rats.     

Levels of hypothalamic neurotransmitters in lean and obese Zucker rats

Hypothalamic neurotransmitter levels were compared between groups of Zucker rats. Animals were grouped by gender, phenotype and preference for dietary fat. Before sacrifice all animals consumed a standard rat chow diet and were fasted overnight. Five rats from each of eight groups were assayed. Hypothalamic regions (lateral, LH; ventromedial, VMH; paraventricular, PVN) and the raphe were isolated and analyzed for dopamine, norepinephrine, epinephrine, serotonin and 5-hydroxyindoleacetic acid. A factorial analysis of variance was used to compare the concentrations of these biogenic amines in the four regions across phenotypic, gender and fat preference profiles. No differences were demonstrated between groups based upon fat food preference. Epinephrine and 5-HIAA content varied between lean and obese animals but there were no differences in the content of serotonin, norepinephrine or dopamine. The results are consistent with the hypothesis that the obese animal eats more because it releases less of the satiety-inducing neurotransmitter serotonin in the hypothalamus.     

Dietary long-chain inulin reduces abdominal fat but has no effect on bone density in growing female rats

New strategies to improve Ca absorption and bone health are needed to address the current state of osteoporosis prevention and management. Inulin-type fructans have shown great promise as a dietary intervention strategy, but have not yet been tested in a young female model. Our objective was to investigate the effect of long chain (LC) inulin on bone mineralization and density in growing, female rats, as well as the quality of growth. Weanling Sprague-Dawley rats were assigned to inulin or cellulose treatments for either 4 or 8 weeks. Growth was measured weekly and quality of growth assessed using fat pad weights and dual-energy X-ray absorptiometry (DXA). Whole body (WB) and selected regions were analysed for bone mineral density (BMD) and body composition by DXA. Serum markers of bone turnover were assessed by enzyme-linked immunosorbent assays. Ca and P concentrations were determined in excised femurs by inductively coupled plasma spectrometry. Feeding inulin resulted in 4 % higher femoral weight (adjusted for body weight) and 6 % less feed intake. Inulin did not affect WB or regional BMD, but was associated with a 28 % lower parametrial fat pad mass, 21 % less WB fat mass and 5 % less WB mass. In summary, LC-inulin lowered body fat mass, without consequence to bone density in growing female rats.     

Effect of fasting on vascular contractility in lean and obese Zucker rats

We compared the effects of fasting (36 h) on blood pressure and aortic contractile responsiveness in lean and obese Zucker rats. Fasting of lean animals resulted in a significant loss in body weight (-9.1 +/- 0.1%) and reduction in systolic blood pressure (-11.4 +/- 1.9 mmHg). Fasting plasma triacylglycerols (-76%) and beta-hydroxybutryic acid (beta-HBA) (+ 218%) were significantly decreased and increased, respectively. The fasting plasma concentrations of insulin (-72%) were significantly decreased, whereas glucose and epinephrine (Epi) were not changed in lean rats. The fasting of obese rats also resulted in weight loss (-5.6 +/- 1.3%) but did not cause a significant reduction of blood pressure. The plasma total cholesterol (+18%) was increased, triacylglycerols (-42%) were decreased and beta-HBA levels were unchanged in fasted obese rats. Similar to lean animals, the insulin levels of fasted obese rats were significantly decreased (-85%), whereas glucose and Epi concentrations were not significantly changed. Fasting of lean animals had no effect on the maximal contractile response of aortae to high K(+) and phorbol 12, 13 dibutyrate (PDBu) but significantly reduced the response to norepinephrine (NE) (% reference: fed, 61.1 +/- 11.0; fasted, 45.6 +/- 4.5). In addition, the concentration for half-maximal response (ED(50)) to NE was increased in fasted lean rats (fed, 1.8+/-0.2 x 10(-8)M; fasted, 3.0+/-0.3 x 10(-8)M). By comparison, fasting of obese rats had no significant effect on the contractile response to K(+), NE, or PDBu. The results show that short-term food withdrawal induces significant changes in vascular contractile properties of lean but not obese rats. Because fasting-induced changes were variable depending on the agonist, the results further suggest that the mechanism did not involve a general loss or enhancement in functional status.     

Carnitine metabolism in lean and obese Zucker rats during starvation

Carnitine metabolism during starvation was studied in adult lean and obese female Zucker rats. Comparisons were made between rats starved for 0, 3, 6 or 9 d. Total plasma carnitine was not affected by obesity or starvation, but free plasma carnitine decreased with starvation. Plasma acid-soluble acylcarnitine was lower in obese than in lean rats, and increased with starvation in both lean and obese rats. Plasma acid-insoluble acylcarnitine was not affected by obesity but increased with starvation. Liver free and acid-soluble acylcarnitine were lower in obese rats than lean rats, and starvation increased liver free carnitine and acid-insoluble acylcarnitine. Free carnitine was lower in muscle from obese rats than from lean rats. In kidney, free carnitine decreased during starvation. Heart carnitine was not affected by obesity or starvation. Urinary free carnitine and acid-soluble acylcarnitine clearance decreased during starvation. These studies indicate that: 1) lean and obese Zucker rats conserve carnitine during starvation; and 2) the decreases in liver carnitine concentration reflect the loss of cellular constituents rather than increases in total hepatic carnitine.     

Effect of bran and cellulose on lipid metabolism in obese female Zucker rats

The effects on lipid metabolism of bran and cellulose added to a low-cholesterol purified diet were studied in female obese Zucker rats. The obese Zucker rat was chosen for the experiment because of its sensitivity to dietary changes with regard to lipid metabolism. Cellulos, as well as bran, had an effect on lipid metabolism, which is expressed as an increase in the excretion of fecal bile acid and cholesterol and, in the case of bran feeding, as a decrease in liver cholesterol level and an increase of fecal fat excretion. The increased excretion rate of cholesterol and bile acids did not result in a reduction of the plasma cholesterol levels, which suggests a compensatory mechanism in the form of either an increase of hepatic cholesterol synthesis and/or changes within the body cholesterol pools. The increased excretion of fecal fat that occurred when bran was added to the diet, is not likely to influence cholesterol metabolism, since fecal fat excretion only appeared to form a small percentage of the total fat intake. Bran as well as cellulose caused a significant increase in fecal wet weight and a decrease in transit time. Though both cellulose and bran are capable of binding bile acid, cholesterol and/or fat, the intestinal transit time and the fecal bulk might also be a cause of increased steroid excretion. The fact that our results are inconsistent with those of some investigations described in the literature but in agreement with the findings of other workers, again stresses the primary need for a better chemical characterization of the various fiber sources.     

Dietary fructans, but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats

This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans.     

Indices of skeletal muscle growth in lean and obese Zucker rats

Skeletal muscle growth was studied in gastrocnemius muscle of lean and obese ad libitum or pair-fed Zucker rats. Skeletal muscle cellularity was determined by DNA, RNA and protein analysis. The length and weight of the tibia and femur were determined. All rats were killed at 15 weeks of age. Lean rats had heavier gastrocnemius, total DNA and total protein than either the ad libitum (ALO) or pair-fed (PFO) obese rats. Lean rats had longer and heavier tibias. Femur length was greater in lean animals while femur weight did not differ between lean and ALO groups. Both had heavier femur than the PFO rats. Comparison of the obese rats revealed that the ALO rats had greater gastrocnemius weight, total DNA and total protein than the PFO group. Total RNA was not different between the lean and ALO group. Comparison of tibias and femurs showed the ALO rats to have longer and heavier bones than the PFO rats. In summary, there are marked differences in the bones of the hindlimb and the cellularity of the gastrocnemius muscle between lean and obese Zucker rats. The differences were accentuated by pair feeding the obese rat.