Effect of diet supplementation with glutamine, dihydroxyacetone, and leucine on food intake, weight gain, and postprandial glycogen metabolism of rats

OBJECTIVE: We tested the hypothesis that increasing the rate of postprandial hepatic glycogen synthesis would decrease food intake and growth rate in normal rats. METHODS: Diets supplemented with glutamine, glutamine plus dihydroxyacetone, and glutamine plus dihydroxyacetone plus leucine were administered to male Sprague-Dawley rats for 1 wk. These are combinations that have been shown to stimulate hepatic glycogen synthesis in vitro. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis. Positional analysis of the 3H incorporated into glycogen was used to determine the proportion of glycogen synthesized via pyruvate. Final levels of plasma glucose and triacylglycerol and hepatic glycogen were also measured. RESULTS: Dietary glutamine increased hepatic glycogen synthesis. Addition of dihydroxyacetone, with or without additional leucine, caused an additional increase in hepatic glycogen synthesis and increased the proportion of glycogen synthesized via pyruvate. Lipogenesis was not altered in the liver or adipose tissue. None of the dietary treatments had any effect on food intake, but the diets that contained dihydroxyacetone decreased the rate of weight gain. CONCLUSIONS: Increasing glycogen synthesis had no effect on food intake. Increasing the proportion of glycogen synthesized by the indirect pathway through pyruvate was associated with a decrease in weight gain.     

Comparison of dehydroepiandrosterone and clofibric acid treatments in obese Zucker rats

The effects of either dehydroepiandrosterone (DHEA) or clofibric acid (CFA) treatment on obese female Zucker rats were compared. After 5 wk of treatment, food intake, body weight gain and food efficiency ratio of DHEA-treated rats were 85, 64 and 75%, respectively, of those of CFA-treated and control rats. Liver weights of DHEA- and CFA-treated rats were higher than those of control rats. Non-fasting serum glucose levels were similar in all groups, but serum insulin level of DHEA-treated rats was 59% of that in CFA-treated and control rats. Results of glucose tolerance tests were not different among the groups. Mitochondrial state 3 and 4 rates expressed per g liver or per liver with either glutamate-malate or succinate as substrate were higher in DHEA-treated rats than in CFA-treated or control rats. Mitochondrial long-chain fatty acyl-CoA hydrolase activity was 8.5 and 4 times higher in DHEA- and CFA-treated rats, respectively, than in control rats. These results suggest that although DHEA and CFA affect some hepatic biochemical parameters similarly, they are distinct in their effects on body weight, serum insulin and mitochondrial respiration in obese Zucker rats.     

Influence of thyroid status on body weight gain, food intake and serum lipid levels in genetically obese Zucker rats

Body weight gain, food intake and serum concentrations of total lipids, cholesterol, triglycerides, phospholipids and free fatty acids were measured in genetically obese and lean female Zucker rats after surgical thyroidectomy and treatment with 3,5,3'-triiodothyronine (T3) (3 micrograms/100 g body wt per day) for 4 wk. There were large differences in the major serum lipids between the control obese and lean rats. Obese rats were characterized by high levels of the various categories of lipids, especially of triglycerides. Thyroidectomized rats had higher serum concentrations of total lipids and cholesterol than controls in both obese and lean rats. The serum concentration of triglycerides was higher in the thyroidectomized lean rats than in lean controls but lower in their thyroidectomized obese littermates than in obese controls. The T3 treatment resulted in a marked reduction in serum total lipid, cholesterol, triglyceride and phospholipid levels in both thyroidectomized and control obese rats. The same treatment given to thyroidectomized and control lean rats also produced a lower concentration in serum total lipid, cholesterol and triglyceride levels but had no significant effect on serum phospholipid levels. The serum concentration of free fatty acid was not significantly affected by T3 administration in either obese or lean rats. Thyroidectomy induced a lower body weight gain in both obese and lean rats. The T3 treatment restored the body weight gain in the thyroidectomized lean rats but not in the thyroidectomized obese rats, although the food intake was increased by T3.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

Time-dependent effects of progressive gamma-linolenate feeding on hyperphagia, weight gain, and erythrocyte fatty acid composition during growth of Zucker obese rats

Obese Zucker rats (fa/fa) have low levels of arachidonic acid (AA) in liver phospholipids (PL). We have previously shown that a 70% gamma-linolenate concentrate (GLA; an AA intermediate) fed at a fixed dose (0.07 g/day) normalized hepatic PL AA and reduced weight gain selectively in the obese animals. In a follow-up study, 16 obese (fa/fa) and 16 lean (Fa/Fa) 4-week-old male rats were randomized into 4 groups of 8 each and gavaged daily with soybean oil (SOY) containing 55% 18:2omega6 (an AA precursor) or GLA, using a progressive dose (< or = 5% of total calories) based on body weight. A defined diet with 11% of energy as SOY was fed ad libitum for 60 days. GLA obese had lower body weight (p<0.0001) and 60-day cumulative food intake (p<0.05) compared to SOY obese, but neither parameter differed between the lean groups. For the last twenty days cumulative food intake was identical for GLA obese and SOY lean, whereas SOY obese consumed 18% more (p<0.05). Thus the progressive dose of GLA selectively suppressed hyperphagia in obese Zucker rats. Erythrocytes collected at 15-day intervals showed parallel increases in AA in both genotypes over time, suggesting normal AA availability during rapid growth. Thus, the reduced PL AA in the livers from the obese rats probably reflects impaired distribution in selected tissues rather than reduced hepatic production. Due to the potential health risks of enriching tissue lipids with AA, great caution is advised in considering GLA as therapy for human obesity.     

Postprandial glycogen and lipid synthesis in prednisolone-treated rats maintained on high-protein diets with varied carbohydrate levels

OBJECTIVE: The present experiment was designed to study the effect of a high-protein, high-carbohydrate diet versus a high-protein, low-carbohydrate diet on in vivo postprandial glycogen and lipid synthesis of rats treated with prednisolone. METHODS: Thirty-two 6-wk-old male Sprague-Dawley rats were randomly assigned to one of four equal groups: high-protein, high-carbohydrate; high-protein, high-carbohydrate with prednisolone; high-protein, low-carbohydrate; and high-protein, low-carbohydrate with prednisolone. Rats were sham operated or subcutaneously implanted with prednisolone pellets while being maintained on their respective diets (39% of energy from protein) for 6 wk. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, overnight-fasted rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose, insulin, and triacylglycerol concentrations and hepatic glycogen content were also measured. RESULTS: Results showed that hepatic glycogen content (milligrams per gram of liver) was similar across all four experimental groups. Total hepatic glycogen synthesis and its percentage synthesis via pyruvate (indirect pathway) were higher in rats maintained on the high-protein, high-carbohydrate diet compared with those on the high-protein, low-carbohydrate diet and this was not substantially affected by prednisolone administration. Hepatic and epididymal fat pad lipid syntheses were not altered by diet or prednisolone treatments. CONCLUSION: Under long-term high-protein conditions, prednisolone administration does not seem to affect hepatic glycogen synthesis, which was increased with the increased carbohydrate content of the diet.     

Effect of treadmill training on muscle oxidative capacity and accretion in young male obese and nonobese Zucker rats

This study was designed to determine if treadmill training of the male obese Zucker rat could reverse its deficit in muscle accretion, expose a possible latent defect in its muscle oxidative capacity or significantly alter its food intake and lipid deposition. At 12 wk of age muscle mass and myofibrillar protein concentration were significantly lower and body lipid and food intake were significantly higher in the sedentary obese than in the nonobese rat. Exercise, by both inducing hypophagia and increasing energy output, led to a lower body weight, body lipid, and muscle mass in the exercised than in the nonexercised rats. This response to exercise did not differ between both phenotypes, except for body lipid. In that case the reduction of body lipid was greater for the obese rats. Muscle mitochondrial enzyme activities and rates of mitochondrial respiration in the obese rats were not different or greater than those of their sedentary or pair-exercised nonobese counterparts. Taken together these data indicate that oxidative capacity per unit of muscle is not significantly lower in the obese rats than in nonobese rats in both sedentary and exercised states, but that total muscle oxidative capacity is lower on a whole-animal basis since total muscle mass is lower. Further, exercise reduces, but does not prevent the enhanced weight gain and lipid accretion that characterizes the obese rat.     

Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats

OBJECTIVE: To investigate whether chronic administration of the long-acting glucagon-like peptide-1 receptor agonist exendin-4 can elicit sustained reductions in food intake and body weight and whether its actions require an intact leptin system. RESEARCH METHODS AND PROCEDURES: Male lean and obese Zucker (fa/fa) rats were infused intracerebroventricularly with exendin-4 using osmotic minipumps for 8 days. RESULTS: Exendin-4 reduced body weight in both lean and obese Zucker rats, maximum suppression being reached on Day 5 in obese (8%) and Day 7 in lean (16%) rats. However, epididymal white adipose tissue weight was not reduced, and only in lean rats was there a reduction in plasma leptin concentration. Food intake was maximally suppressed (by 81%) on Day 3 in obese rats but was reduced by only 18% on Day 8. Similarly, in lean rats food intake was maximally reduced (by 93%) on Day 4 of treatment and by 45% on Day 8. Brown adipose tissue temperature was reduced from Days 2 to 4. Plasma corticosterone was elevated by 76% in lean but by only 28% in obese rats. DISCUSSION: Chronic exendin-4 treatment reduced body weight in both obese and lean Zucker rats by reducing food intake: metabolic rate was apparently suppressed. These effects did not require an intact leptin system. Neither does the absence of an intact leptin system sensitize animals to exendin-4. Partial tolerance to the anorectic effect of exendin-4 in lean rats may have been due to elevated plasma corticosterone and depressed plasma leptin levels, but other counter-regulatory mechanisms seem to play a role in obese Zucker rats.     

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.     

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.     

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.     

LY226936 administered orally and centrally to obese Zucker rats suppresses food intake and body weight gain

LY226936, methylcarbamothoic acid-S-(4,5-dihydro-2-thiazolyl) ester, is a new compound that, when administered to obese Zucker rats, caused reduced food intake. LY226936 reduced the food consumption after a single oral dose of 50 and 100 mg/kg. On chronic oral administration to meal-fed obese (5 to 35 mg/kg. once daily) and to fed obese and lean (15 mg/kg. twice daily) Zucker rats, LY226936 reduced food intake and body weight gain for periods ranging from 40 to 48 days. The effect on both parameters was statistically significant. There is no evidence in our studies that tolerance to the actions of LY226936 developed. LY226936 decreased the consumption of both high carbohydrate and high fat diets. Food consumption of meal-fed obese Zucker rats was reduced significantly each time a single dose of 10 ugm LY226936 per rat was infused intracerebroventricularly. None of the receptors studied (mu and kappa opioid, CCK, serotonin, neuropeptide Y, galinin, N-methyl-D-aspartic acid) appeared to bind LY226936 and therefore, appear not to be involved in the depression of food intake by the obese Zucker rat.     

Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats

We studied the influence of oligofructose (OFS), a nondigestible fructan, on lipid metabolism in obese fa/fa Zucker rats. The addition of 10 g/100 g OFS to the diet slowed the increase in body weight without modifying serum triglycerides or glucose concentrations after 7 wk of treatment. However, an oral load of 2 g glucose and 5 g corn oil/kg body weight increased triglyceridemia more in OFS-fed rats than in control rats. After 10 wk, OFS decreased the hepatic concentration of triglycerides 57% relative to controls. The less severe steatosis was confirmed by histologic analysis. Among the key enzymes involved in fatty acid synthesis and esterification, only malic enzyme activity was significantly lower in OFS-fed rats than in controls. The epididymal fat mass was significantly lower in OFS-fed rats. In conclusion, dietary enrichment with OFS can counteract both the fat mass development and the hepatic steatosis that occur in obese Zucker rats. Future studies will be designed to clarify in obese animals the influence of dietary OFS on postprandial triglyceridemia, which is an important variable associated with the development of atherosclerosis in humans, and to analyze the biochemical mechanism underlying the "hepatoprotective" effect of OFS.     

A diet supplemented with husks of Plantago ovata reduces the development of endothelial dysfunction, hypertension, and obesity by affecting adiponectin and TNF-alpha in obese Zucker rats

The aim of the present study was to analyze whether consumption of a fiber-supplemented diet containing 3.5% Plantago ovata husks prevented many of the abnormalities clustered in the metabolic syndrome, including obesity, dyslipidemia, hypertension and endothelial dysfunction. For this purpose, obese Zucker rats, a model of type 2 diabetes, and their lean littermates were studied. Rats consumed a standard control diet or that diet supplemented with 3.5% P. ovata husks for 25 wk. Body weights were measured weekly. Systolic blood pressure (SBP) was measured monthly. At the end of the treatment, plasma concentrations of triglycerides, total cholesterol, FFAs, glucose, insulin, adiponectin, and tumor necrosis factor alpha (TNF-alpha) were determined, and studies on vascular function were performed using aortic rings. Rats fed the P. ovata husk-supplemented diet had a significantly reduced body weight gain compared with those fed the standard diet. Decreased endothelium-dependent relaxation in response to acetylcholine (ACh) by aortic rings from obese Zucker rats was improved in those fed the fiber-supplemented diet. The greater SBP, higher plasma concentrations of triglycerides, total cholesterol, FFA, glucose, insulin, and TNF-alpha, and the hypoadinectinemia that occurred in obese Zucker rats that consumed the control diet were significantly improved in those fed the fiber-supplemented diet. We conclude that intake of a P. ovata husk-supplemented diet prevents endothelial dysfunction, hypertension, and obesity development, and ameliorates dyslipidemia and abnormal plasma concentrations of adiponectin and TNF-alpha in obese Zucker rats.     

A comparison of the effects of dehydroepiandrosterone treatment to adlibitum and pair-feeding in the obese zucker rat

In general, treatment of mice and rats with dehydroepiandrosterone (DHEA) has been shown to result in a decrease in body weight gain without an effect on food intake. The obese Zucker rat has been the exception. The present study compares the response of DHEA-treated obese rats to both adlibitum-fed and pair-fed obese groups. Body weight, weight gain and food efficiency ratio were all significantly decreased in DHEA-treated rats compared with either adlibitum-fed or pair-fed rats. Liver weight was higher and heart weight lower in the DHEA-treated group in comparison to both control groups. Retroperitoneal fat pad weight was lowered in DHEA-treated rats by over 60% compared to both pair-fed rats and adlibitum-fed rats. Similar results were found for parametrial fat pads. Neither fecal fat excretion nor urinary output were altered by DHEA treatment. The finding of greater activity of the enzyme, long chain acyl-CoA hydrolase, in DHEA-treated but not in either adlibitum-fed or pair-fed rats, supports our hypothesis that DHEA may induce a futile cycle of fatty acid metabolism leading to enhanced energy utilization. These results support fundamentally different effects of DHEA compared to a decreased food intake in the obese Zucker rat.     

Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.     

Thermogenic and antiobesity activity of a novel beta-adrenoceptor agonist (BRL 26830A) in mice and rats

The effects of a novel compound, BRL 26830A, on energy balance in normal and obese mice have been investigated. BRL 26830A reduced body weight or weight gain in genetically (ob/ob), goldthioglucose, and cafeteria diet obese mice and genetically obese (fa/fa) Zucker rats. Weight reduction was due to reduced body lipid content. BRL 26830A caused little or no reduction in food intake in these animals but it increased metabolic rate and in genetically obese mice this thermic effect was increased by repeat dosing. BRL 26830A did not reduce body weight gain in the lean counterparts of the genetically obese animals. Its thermic effect was smaller in the lean than the genetically obese mice and it caused an increase in food intake in the lean mice. The thermic effect of BRL 26830A was inhibited by dl- but not d-propranolol. BRL 26830A largely overcame the depression in metabolic rate caused by fasting.     

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.