Response of adult lean and obese female Zucker rats to food restriction and refeeding

Lean and obese female Zucker rats were either fed ad libitum (ad libitum-fed lean and ad libitum-fed obese), food-restricted (restricted lean and restricted obese) at 50% of ad libitum intake for 3 weeks from 19–20 weeks of age, or food-restricted and then refed ad libitum for 1 week (restricted-refed lean and restricted-refed obese). Following food restriction, body weights of restricted rats were significantly lower than ad libitum-fed rats within genotype. Body weights of restricted-refed rats were not different from either ad libitum-fed or restricted rats within genotype. Restricted-refed lean rats returned to their previous ad libitum food intake, whereas restricted-refed obese rats ate significantly more food. Both restricted and restricted-refed lean rats had lowered serum insulin levels compared to ad libitum-fed lean rats, whereas there was no effect on serum insulin levels in obese rats. Liver weights and hepatocyte conversion of glucose to fatty acids, glyceride-glycerol and CO₂ were not affected by food restriction or refeeding in lean rats. Among obese rats, restricted obese rats had the smallest liver weights, and restricted-refed obese rats had the highest. Restricted-refed obese rats had greater rates of hepatic glucose metabolism compared to all other groups. Ad libitum-fed lean and restricted-refed lean rats had similar fat pad weights that were significantly greater than those of restricted lean rats. Dietary intervention had no effect on fat pad weight in obese rats. There was no effect of food restriction or refeeding on adipocyte glucose metabolism except for higher glucose conversion to CO₂ for restricted lean rats in comparison to values for all other groups. These results demonstrate that body weight changes of adult female obese rats in response to food restriction and refeeding are similar to those of lean rats; but the effects of liver and adipose tissue weights are different.     

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.     

Effects of a fat substitute, sucrose polyester, on food intake, body composition, and serum factors in lean and obese Zucker rats

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.     

Effects of long-term moderate food restriction on growth, serum factors, lipogenic enzymes and adipocyte glucose metabolism in lean and obese Zucker rats

The effects of long-term moderate food restriction were assessed in lean and obese male Zucker rats. A 30% reduction in food intake from 5 to 68 wk of age resulted in parallel lowering of body weight in both lean and obese rats compared to their respective ad libitum-fed control groups. In lean rats, epididymal and retroperitoneal fat pad weights and cell size were lowered by food restriction. In obese rats there was an effect of food restriction on growth of the epididymal pad but not the retroperitoneal pad. Hyperinsulinemia, hyperlipidemia and elevated serum albumin levels, as well as higher activity of lipogenic enzymes, were also not affected by food restriction in the obese rat. In a second experiment, long-term food restriction resulted in greater glucose conversion to CO2 in response to insulin in adipocytes from lean rats but not obese rats compared to their respective control groups. These results indicate that food restriction throughout the first year of life in the obese Zucker rat does not alter the development of hyperplastic obesity and insulin resistance.     

Body weight, body composition, and energy metabolism in lean and obese Zucker rats fed soybean oil or butter.

BACKGROUND: Dietary fat composition is thought to affect body weight regulation independent of the amount of fat ingested. OBJECTIVE: We analyzed the feeding behavior, body weight gain, body composition, and energy metabolism in lean and obese rats fed a diet in which fat was in the form of either butter or soybean oil. DESIGN: Ten lean (Fa/?) and 10 obese (fa/fa) adult Zucker rats were divided into 4 groups according to a 2 x 2 experimental design. They were fed a normally balanced diet over 11 wk in which 30% of energy was either soybean oil or butter. Food intake, body weight gain, and body composition were measured. Indirect calorimetry was used to study energy metabolism at rest and in relation to feeding and activity. RESULTS: Food intake increased similarly in lean and obese rats after butter feeding. Body weight gain increased in obese rats and decreased in lean rats after butter feeding. Body weight gain in obese rats was due mainly to an increase in the weight of lean tissues besides muscle, whereas adiposity and distribution of fat between the various pads did not change. Resting metabolic rates and postprandial lipid oxidation increased in butter-fed obese rats. Lipid oxidation during exercise was not significantly different between obese and lean rats. Fat oxidation increased in butter-fed lean rats during treadmill running at moderate intensity. CONCLUSIONS: In obese rats, basal metabolism and postprandial lipid oxidation increased during butter feeding, which appeared to prevent fat accumulation in the long term. In lean rats, butter feeding favored lipid utilization by working muscles, an observation that deserves further investigation in terms of endurance and performance.     

Consequences of restricted feeding/refeeding cycles in lean and obese female Zucker rats

Lean and obese female Zucker rats underwent four, 6-wk cycles of restricted feeding/refeeding. Restricted-fed, lean (RL) rats lost and then regained sufficient weight in each cycle to weigh the same amount as ad libitum-fed, lean (AL) rats at the end of each refeeding period. After the final period of restricted intake, RL rats had significantly lower parametrial and retroperitoneal pad weights and fat cell sizes than AL rats, but their organ growth and lipogenic enzymes were not affected. After the final refeeding period, there were no differences between RL and AL rats except in cumulative food intake. During the first period of restricted intake restricted-fed, obese (RO) rats did not lose weight; however, they were unable to attain the body weight of ad libitum-fed, obese (AO) rats during the subsequent refeeding period. In later cycles, RO rats lost and regained weight, but always weighed significantly less than AO rats. Following the final restricted feeding and refeeding periods, fat pad weights and cell numbers were significantly lower in RO than AO rats, but fat cell size was not affected. Liver weight and lipogenic enzymes were lower in RO than in AO rats after the final period of restricted intake, but were similar to AO rats after the final refeeding period. Permanent effects on heart and kidney growth were found in RO rats. Obese rats appeared to respond differently than lean rats to this form of dietary intervention.     

Response of adult lean and obese female Zucker rats to intermittent food restriction/refeeding

Previously, it was found that lean and obese Zucker rats (9-15 wk of age) responded differently to the first of four cycles of food restriction/refeeding. In later cycles, they responded similarly. The present study was undertaken to determine if this finding was due to age, adaptation to the intervention or the obesity. Adult (35-wk-old) lean and obese rats were classified into four groups, ad libitum-fed lean and obese and food-restricted lean and obese. Food-restricted rats underwent four 3-wk periods when they were fed 50% of their ad libitum intake, each followed by a 3-wk period of ad libitum refeeding. Food-restricted rats lost and regained sufficient weight in each cycle to weigh a similar amount as their ad libitum-fed groups by the end of each refeeding period. In lean rats, there were no permanent effects of this intervention except for a 25% reduction in carbohydrate intake. Similar results were found in obese rats, although they did have significantly lower retroperitoneal fat pad weight and serum triacylglycerol levels than ad libitum-fed obese rats at the end of the experiment. These results indicate that lean and obese adult rats respond to each food restriction/refeeding cycle in a similar manner. Results in the earlier experiment would appear to be due both to age and genotype.     

Adaptations of adult lean and obese zucker rats during food restriction

The adaptations that occur during prolonged food restriction of adult lean and obese Zucker rats were examined. Lean Zucker rats were restricted until they lost 31% (RL-31) or 42% (RL-42) of their starting weight. Obese Zucker rats were restricted until they lost 53% (RO-53) or 78% (RO-78) of their initial weight. Weights of five skeletal muscles, three fat pads and two organs were determined. During restriction, the obese rats catabolized less muscle protein per day than the lean animals. The percentage of muscle lost by the obese was lower than the percentage body weight loss. After prolonged restriction, both lean and obese rats were essentially depleted of fat stores. Obese rats relied to a greater extent on fat stores for energy and to a lesser extent on catabolism of lean body mass than lean rats. The ratios of protein/DNA and RNA/DNA were significantly reduced in muscles from all restricted animals and the DNA content was lower in the groups that lost the most weight (RL-42 and RO-78). In conclusion, obese Zucker rats have an enhanced ability to adapt to restriction with a slower rate of skeletal muscle catabolism. However, “survival” during prolonged restriction is dependent on the initial amount of adipose tissue and not loss of a critical amount of lean body mass.     

Effects of food restriction and refeeding on adipocyte glucose metabolism in Zucker rats

Chronic food restriction has been shown to enhance glucose metabolism in adipocytes from lean Zucker rats at 10, 26, and 52 weeks of age compared to ad libitum-fed lean rats. Only adipocytes from food restricted 10-week-old obese rats demonstrated this response. In this study, lean and obese rats were food restricted from 5 until 14 weeks of age to determine the age at which adipocytes from obese rats were no longer affected by this intervention. Effects of 1 week of refeeding were also determined. When the rats were killed, body weights were highest in control rats followed by restricted/refed and then restricted rats within each genotype. Epididymal pad weights of lean rats were resistant to dietary intervention, while those of obese-restricted and obese-restricted/refed rats weighed less than pads of obese-control rats. Retroperitoneal pad weight was lowered by food restriction in both genotypes; but only that of lean-restricted/refed rats totally recovered with refeeding. Adipocytes of lean-restricted rats had the highest conversion of glucose to CO₂. Glyceride-glycerol production was higher in obese compared to lean rats, but restricted rats had elevated conversion of glucose to fatty acids. In general, these results indicate that by 14 weeks of age obese Zucker rats no longer respond to food restriction with an elevated rate of glucose metabolism in adipocytes.     

Effects of short-term dehydroepiandrosterone treatment on serum and pancreatic insulin in Zucker rats

Lean and obese female Zucker rats were treated with 0.6% dehydroepiandrosterone (DHEA) from 5 until 10 wk of age and comparisons made to both ad libitum--fed and weight-matched groups. Within genotype, body weights and cumulative food intakes of DHEA and weight-matched groups were not different. Fat pad weights of DHEA rats were significantly lower than those of non-treated groups. Pancreatic insulin content, whether expressed per pancreas or per gram pancreas, was not lowered by DHEA treatment. Fasting serum insulin levels were not altered in lean rats but were significantly lower in DHEA obese rats than in either nontreated obese group. Glucose metabolism (conversion to CO2, fatty acids or glyceride-glycerol) in isolated adipocytes was similar in all groups except that obese rats had greater glyceride-glycerol production than lean rats. Glucose conversion to CO2 in soleus muscle was lower in obese rats than in lean rats. Basal and insulin-stimulated glycogen production was lower in DHEA and weight-matched obese rats than in any other group. Ad libitum-fed lean rats had higher insulin-stimulated glycogen production than DHEA lean and all groups of obese rats. Short-term DHEA treatment of obese Zucker rats lowers serum insulin levels without improvement of insulin resistance in peripheral tissues and without lowering pancreatic insulin content.     

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.     

Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats

OBJECTIVE: This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats. RESEARCH METHODS AND PROCEDURES: A 2 x 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg). RESULTS: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals. DISCUSSION: The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.     

Effects of dehydroepiandrosterone treatment in rats with diet-induced obesity

Previous studies showed that administration of dehydroepiandrosterone (DHEA) to lean and genetically obese Zucker rats reduced body weight. In the present experiments, the effect of DHEA treatment in rats with diet-induced obesity was evaluated. In experiment 1, male Sprague-Dawley rats (300 g) were fed a nonpurified diet (reference group) or a condensed milk-corn oil nonpurified diet [diet-induced obese (DIO) rats] for 7 wk. Then, 0.6% DHEA was included in the food of one-half of the DIO rats (DIO + DHEA rats). After 6 wk, DIO rats weighed 23% more and had greater fat pad weights, cell size and cell number than reference and DIO + DHEA rats. Brown fat mitochondrial respiration was similar in all groups. DIO rats had higher serum cholesterol and triacylglycerol concentrations than reference and DIO + DHEA rats. DIO + DHEA rats had lower serum insulin levels than DIO and reference rats. In experiment 2, male Sprague-Dawley rats (460 g) were fed either the nonpurified diet or the condensed milk diet for 8 wk. Condensed milk-fed rats were then divided into DIO and diet-resistant groups. One-half of the rats in each group were fed 0.6% DHEA for 2 wk. Body weights and serum glucose, insulin, triacylglycerol and triiodothyronine levels were lowered by DHEA treatment in all groups. Liver mitochondrial state 3 respiration rates per gram and per liver and peroxisomal beta-oxidation were higher in DHEA-treated than in control rats. In DIO rats, DHEA treatment appears to interfere with hyperplastic adipose tissue growth. In this strain of rats, DHEA appears to have hypolipidemic and hypoinsulinemic effects.     

Characteristics of the obesity syndrome in Zucker-Brown Norway (ZBN) hybrid rats

The existence of a restriction fragment length polymorphism (RFLP) closely linked to the fatty locus between the Zucker (Z) and Brown Norway (BN) rat strains allows evaluation of early effects of the fatty (fa) gene using offspring of back-crosses (N2) between F1 females and Zucker obese males. We examined several metabolic characteristics of N2 animals to determine if these hybrid animals exhibited similar characteristics of the obese syndrome to those of Zucker rats. Females from crosses of obese male Zucker (fa/fa) and lean female BN (+/+) rats were back-crossed to their sires, resulting in twelve N2 litters. At 9 weeks of age, liver, spleen, interscapular brown fat (IBAT), and gonadal, retroperitoneal (RP), and inguinal fat depots were removed and weighed. Samples of the RP depot were analyzed for cell size and number. Obese N2 rats were hyperphagic, with body weights in the range of those of obese Zucker rats. Obese N2 rats were also hyperinsulinemic [mean +/- SEM, microU/ml: females, 7.9 +/- 0.6 vs. 82.1 +/- 8.4 (lean vs. obese); males, 10.5 +/- 1.6 vs. 128.5 +/- 13.4 (lean vs. obese)] and mildly hyperglycemic [mean +/- SEM, mg/dl: females, 104.1 +/- 2.0 vs. 139.0 +/- 14.7 (lean vs. obese); males, 100.9 +/- 2.6 vs. 132.0 +/- 2.8 (lean vs. obese) p < or = 0.05]. White fat depots in obese rats were 3 to 7 times heavier than those in lean rats; adipocyte numbers in RP depots were 50% greater in obese than in lean rats; and cell size was more than 3 times larger. IBAT, liver, and spleen were also heavier in obese vs. lean rats, while tail lengths were shorter. Percent lean carcass mass and % carcass protein were about 30% greater in lean vs. obese rats, while % carcass fat in obese rats was 5 times greater than that of lean rats. Thus, phenotypic expression of the fa gene in ZBN hybrid animals, with approximately 25% of their genetic background coming from the BN strain, appears to be similar to that in Zucker rats. Given the similarity of phenotypic expression of the fa gene between the Zucker strain and ZBN hybrids, it is plausible to consider using ZBN hybrids for studies of early manifestations of fa gene action prior to onset of detectable obesity.     

Insulin resistant glucose transport activity in adipose cells from the SHR/N-corpulent rat

Young male obese (cp/cp) and lean (cp/+ or +/+) littermates of the SHR/N-corpulent (cp) strain were fed purified diets containing 54% carbohydrate as either sucrose or cooked starch for 12 wk. A significant effect of phenotype (obese greater than lean) was observed on body weight, epididymal fat pad weight and fat cell size. A diet effect (sucrose greater than starch) was observed on body weight, fat pad weight, and fat cell size. No effect of phenotype or diet was observed on basal 3-O-methylglucose transport in isolated adipose cells. However, insulin-stimulated glucose uptake was decreased 70-80% in isolated adipose cells from obese SHR/N-cp rats. No effect of diet on insulin-stimulated glucose uptake was observed in obese SHR/N-cp rats. Scatchard analysis of insulin binding data demonstrated no differences in the dissociation constant (KD) for the insulin receptor:insulin complex. However, obese rats exhibited a decreased number of insulin receptors compared to lean SHR/N-cp rats. These data demonstrate that the obese SHR/N-cp rat exhibits insulin-resistant glucose transport. This altered insulin sensitivity may be one factor contributing to the development of noninsulin-dependent diabetes mellitus in these animals.     

The presence of the "fa" gene in heterozygous (FA/fa) lean female rats, effects on body weight, body fat and serum leptin.

OBJECTIVE: In previous studies, suckling lean heterozygous (FA/fa) pups had higher body fat levels in comparison to lean homozygous (FA/FA) pups. However, in older male rats fed either low- or high-fat diets, we found no effects of the "fa" gene in heterozygous lean rats compared to homozygous lean rats. Other studies have reported effects of the "fa" gene on aspects of insulin metabolism for lean heterozygous female rats compared to their homozygous counterparts. In the present study, the effect of the "fa" gene on body weight and body fat in lean female rats was investigated. RESEARCH METHODS AND PROCEDURES: Homozygous lean female rats were obtained by mating homozygous lean male and female rats. Heterozygous lean female rats were obtained by mating homozygous obese male rats with heterozygous lean female rats. Following weaning, rats were maintained on a standard laboratory diet until 10 weeks of age when they were killed after an overnight fast. RESULTS: Body weight (p<0.03) and inguinal (p = 0.01) and combined retroperitoneal+parametrial (p = 0.06) fat pad weights were heavier in heterozygous lean compared to homozygous lean female rats. Combined fat pad-to-body weight ratio (p = 0.05) and fat cell sizes (p = 0.06) were also higher in the heterozygous lean compared to homozygous lean rats. No differences in serum triacylglycerol, cholesterol, glucose, or insulin concentrations were found between the two groups, but serum leptin levels were significantly higher (p<0.004) in heterozygous lean rats. DISCUSSION: These results indicate that effects of the "fa" gene are present during the postweaning period in lean female rats. Implications for increased body fat and leptin with respect to sexual maturation and fertility are discussed.     

Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats

We have demonstrated previously that a diet containing skimmed milk (SM) fermented by Lactobacillus gasseri SBT2055 (LGSP) reduces adipocyte size in Sprague-Dawley rats. Two experiments were conducted to extend these observations in order to elucidate the mechanism involved. In experiment 1, lean and obese Zucker rats were fed a diet containing SM or LGSP for 4 weeks. The LGSP diet, compared with the SM diet, resulted in lowering of the mesenteric adipose tissue weight (23 %; P < 0.05), adipocyte sizes (28 %; P < 0.001) and serum leptin concentration (36 %; P < 0.05) in lean rats. Obese Zucker rats did not display such dietary effects. Only the number of smaller adipocytes was increased (P < 0.05) by the LGSP diet in the subcutaneous adipose tissue of obese rats. The LGSP diet significantly reduced the serum and hepatic cholesterol in rats. In addition, the LGSP diet led to an increased excretion of faecal fatty acids and total neutral faecal sterols in both rat strains. In experiment 2, Sprague-Dawley rats with permanent cannulation of the thoracic duct were fed either the SM or LGSP diets and their lymph was collected. The LGSP diet lowered the maximum transport rate of TAG and phospholipids. These results indicate that fermented milk regulates adipose tissue growth through inhibition at the stage of dietary fat absorption in lean Zucker rats.     

Trimethyllysine metabolism in lean and obese zucker rats during fasting

The effect of starvation upon the metabolism of trimethyllysine in lean and obese female Zucker rats was studied. All rats were fed a carnitine and trimethyllysine limiting diet for one to two weeks before starvation was initiated. Fed rats and rats starved for three, six, and nine days were used. Liver free and peptide-linked trimethyllysine, and urine total trimethyllysine were measured. Lean and obese Zucker rats had similar hepatic-free and peptide-linked trimethyllysine content when expressed per g protein or per mg DNA. Obese Zucker rats excreted more total trimethyllysine during starvation relative to lean rats. Starvation did not affect trimethyllysine excretion over time, although there were significant decreases in total carnitine excretion in both lean and obese starved rats. Both phenotypes demonstrated a high efficiency of entry of trimethyllysine into the carnitine biosynthetic pathway. We conclude that lean and obese female Zucker rats, similar to male Sprague-Dawley rats, are extremely efficient in the conversion of trimethyllysine into carnitine.     

Conjugated linoleic acid (CLA), body fat, and apoptosis

OBJECTIVE: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for < or =2 weeks on body fat, energy expenditure, and feed intake. RESEARCH METHODS AND PROCEDURES: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation. RESULTS: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption. DISCUSSION: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.     

Cholinesterase activity in the serum and liver of Zucker fat rats and controls

Serum and liver cholinesterase activity was observed to be significantly higher in chow fed Zucker fat rats than in chow fed lean controls. Similarly, serum triglycerides and insulin showed significantly higher levels in the fat rats compared to the controls. In contrast, no significant difference was observed for adipose tissue cholinesterase, serum glucose and cholesterol.Correlation analyses revealed a positive correlation between serum and liver cholinesterase activity when data were combined from both obese and lean rats indicating liver as the possible source of cholinesterase. Serum cholinesterase also correlated positively with triglycerides, body weight and food intake. Food intake also showed a strong positive correlation with serum triglycerides and body weight.