Changes in environmental temperature influence leptin responsiveness in low- and high-fat-fed mice.

Loss of body fat in leptin-treated animals has been attributed to reduced energy intake, increased thermogenesis, and preferential fatty acid oxidation. Leptin does not decrease food intake or body fat in leptin-resistant high-fat (HF)-fed mice, possibly due to a failure of leptin to activate hypothalamic receptors. We measured energy expenditure of male C57BL/6 mice adapted to low-fat (LF) or HF diet and infused them for 13 days with PBS or 10 mug leptin/day from an intraperitoneal mini-osmotic pump to test whether leptin resistance prevented leptin-induced increases in energy expenditure and fatty acid oxidation. There was no effect of low-dose leptin infusions on either of these measures in LF-fed or HF-fed mice, even though LF-fed mice lost body fat. Experiment 2 tested leptin responsiveness in LF-fed and HF-fed mice housed at different temperatures (18 degrees C, 23 degrees C, 27 degrees C), assuming that the cold would increase and the hot environment would inhibit food intake and thermogenesis, which could potentially interfere with leptin action. LF-fed mice housed at 23 degrees C were the only mice that lost body fat during leptin infusion, suggesting that an ability to modify energy expenditure is essential to the maintenance of leptin responsiveness. HF-fed mice in cold or warm environments did not respond to leptin. HF-fed mice in the hot environment were fatter than other HF-fed mice, and, surprisingly, leptin caused a further increase in body fat, demonstrating that the mice were not totally leptin resistant and that partial leptin resistance in a hot environment favors positive energy balance and fat deposition.

Nutritional effects of enzymatically modified soybean oil with caprylic acid versus physical mixture analogue in obese Zucker rats.

Enzymatically modified soybean oil with caprylic acid (SL), a physical mixture of tricaprylin and soybean oil (PHY), and soybean oil as control were fed (20% of diet weight) to female obese Zucker rats. Both lipids (SL and PHY) have similar total fatty acid composition containing 23.4 mol % caprylic acid (C8:0) but have different lipid structures. After 21 days of feeding, the body weight gain was 36.4% in the SL-fed group and 35.2% in the PHY-fed group, respectively; whereas the body weight of the control group increased 41.6%. Significant differences in the respiratory exchange ratio were observed between the SL and PHY groups. However, the contents of glucose, total and high density lipoprotein (HDL) cholesterol, and very low density and low density lipoprotein (VLDL + LDL) cholesterol in serum were not significantly different between the SL- and PHY-fed groups or among the three dietary groups (control, SL, and PHY) (p < 0.05). On the other hand, plasma total cholesterol and plasma triacylglycerol (TAG) were significantly higher in SL- and PHY-fed groups than in the control group. In the liver and inguinal adipocyte TAG, C8:0 was found in the SL-fed group, whereas it was not observed in the liver and inguinal adipocyte TAG of the PHY-fed group, which suggests that positional distribution of C8:0 of the TAG molecule is an important consideration in the metabolism of lipids. This study showed that different positional distribution in TAG molecules lead to different metabolic fates, resulting in the change of fatty acid composition in liver and inguinal adipose TAG in female Zucker rats.

Attenuation of circadian rhythms of food intake and respiration in aging diabetes-prone BHE/Cdb rats.

The hypothesis that BHE/Cdb rats with mutations in their mitochondrial genome might accommodate this mutation by changing their food intake patterns was tested. Four experiments were conducted. Experiments 1 and 2 examined food intake patterns of BHE/Cdb rats fed a stock diet or BHE/Cdb and Sprague-Dawley rats fed a high-fat diet from weaning. Experiment 3 examined the daily rhythms of respiration and heat production in these rats at 200 days of age. Experiment 4 examined the effects of diet composition on these measurements at 50-day intervals. The Sprague-Dawley rats, regardless of diet, had the typical day-night rhythms of feeding and respiration. In contrast, the BHE/Cdb rats fed the high-fat diet showed normal rhythms initially, but with age, these rhythms were attenuated. The changes in rhythms preceded the development of glucose intolerance.

Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number.

We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine the effects on growth performance and fat mass. There was no effect of CLA on growth rate or food intake. Dietary CLA reduced retroperitoneal fat pad weight 13, 25 and 32% in rats fed 0.25 and 0. 5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.05). Similar effects were observed in the parametrial fat pad. The reduced pad size was due to smaller adipocyte size rather than a reduced cell number. Relative to the control group, mean cell volume was 15, 28 and 29% lower in tissue from rats fed 0.25 and 0.5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.01). In the second study, rats were fed CLA (0 vs. 0.5%) for 7 or 49 d. Reductions in fat pad weight were observed within 7 d. In addition, the effects of CLA on energy metabolism were studied in the chronically fed rats. There were no significant effects of CLA on oxygen consumption, CO(2) or heat production. During wk 4 of feeding, but not at other times, there was a 5% lower respiratory quotient in CLA-fed rats (P < 0.05). There was a time-dependent accumulation of CLA in adipose tissue and a decrease in monounsaturated fatty acids. These results suggest that the reduction in fat mass in rats fed CLA can be accounted for by a reduction in cell size rather than a change in cell number.

Metabolic responses to intracerebroventricular leptin and restricted feeding.

Leptin is a hormone secreted by adipocytes, which plays an important role in the control of food intake and metabolic processes. In the current study, a dose-dependent relationship was shown between a bolus intracerebroventricular rat recombinant leptin administration and reductions in food intake and body weight in Sprague-Dawley rats. During the 24 h postinjection period, food intake was decreased by 24, 26, and 52% with 0.625, 2.5, and 10 microg of leptin, respectively. Body weight was reduced by 2, 3, and 5% at 24 h after leptin administration at the doses of 0.156, 2.5, and 10 microg, respectively. Furthermore, indirect calorimetry demonstrated that five daily i.c.v. injections of leptin resulted in an increase in heat production per unit of metabolic body size and fat oxidation by approximately 10 and 48%, respectively. In contrast, food-restricted rats that consumed the equivalent amount of food as leptin-treated rats for 5 days decreased their energy expenditure by 10%. Food restriction was found to decrease respiratory quotient in a similar pattern as the leptin administration. When ad lib feeding was resumed, food-restricted rats quickly recovered their normal food intakes, body weights, and metabolism. Conversely, leptin treatment has prolonged effects on body weight resulting from different metabolic responses than food restriction. Leptin not only suppresses food intake, but also enhances energy expenditure to reduce fat depots.

Responses of lean and obese Zucker rats to centrally administered leptin.

Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the leptin receptor gene. One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation. Obese Zucker rats are unable to respond behaviorally to leptin which is peripherally administered. However, conflicting reports exist on whether obese Zucker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin and to compare the responses of lean and obese Zucker rats. We found that both lean and obese Zucker rats had similar body weight and food intake responses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5, 5, and 10 microg), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also decreased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exhibited different recovery responses. It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ventricles.

Dietary fat type and level influence adiposity development in obese but not lean Zucker rats.

The development of obesity is influenced by a variety of factors including genetics and dietary fat type and level. To examine the interaction between these factors, male lean and obese Zucker rats (5 weeks initial age) were fed either a low-fat (15% calories) or one of two high-fat diets (65% calories; predominant fat source of either soybean oil or palm olein) for 8 weeks. Body weight, food intake, indirect calorimetry, and body composition determinations were performed. As expected, food intake, body weight, feed efficiency, oxygen consumption, heat production and carcass lipid were all significantly higher in obese compared to lean rats. Dietary fat level and/or type influenced body weight gain, oxygen consumption, heat production, energy balance, and carcass weight and lipid content in the obese but not in the lean Zucker rats. Oxygen consumption and carcass weight were increased approximately 25% and 10% respectively in obese rats fed either of the two high-fat diets as compared to those fed the low-fat diet. The type of fat fed in the high-fat diets also influenced body weight gain, heat production, energy balance, and carcass lipid content of the obese rats. Body weight gain and carcass lipid content were increased (16%-17%; P < 0.005) in obese rats fed the high-fat palm olein diet as compared to those fed the low-fat diet. These parameters were not increased in obese rats fed the high-fat soybean oil diet. In contrast, indirect calorimetry measurements indicated a moderate increase in heat production (Kcal/effective body mass/day; 14.5%) and decrease in energy balance (44.8%) in the obese rats fed the high-fat soybean oil diet as compared to those fed the low-fat diet. Energy expenditure and lipid accumulation were negligibly influenced by dietary fat level or type in the lean Zucker rats. The differential response of the lean and obese Zucker rats to this short-term dietary manipulation demonstrate that genetic background can influence an individual's response to dietary fat type and level. The genetically obese Zucker rat appears to be a good model for further studies of high-fat diet-induced obesity.

Whole body composition of rats determined by dual energy X-ray absorptiometry is correlated with chemical analysis.

The use of dual energy X-ray absorptiometry (DXA) is increasing in animal research, but data comparing whole body composition by DXA and chemical analysis (CHEM) in rats are limited. Lean and obese Zucker female rats were used to compare DXA (QDR1000W, Hologic, Waltham, MA) values with CHEM data for percent fat (%FATDXA, %FATCHEM), lean body mass (%PROTDXA, %PROTCHEM) and bone mineral content (%BMCDXA, %ASHCHEM). Four groups of rats (n = 9) were tested for differences in body composition due to consumption of a 100 g guar gum supplement/kg to see if DXA was as sensitive as CHEM in detecting body composition differences induced by diet. The study was analyzed using a split-plot ANOVA where the main plot was a 2 x 2 factorial with phenotype (obese or lean) and treatment (guar gum or control) as the effects, and the subplot was method of detecting body composition (DXA and CHEM), which was treated as a repeated measure. Absolute values for percent fat differed significantly (P < 0.0001) between the two methods as %FATDXA was consistently higher than %FATCHEM. There was not a statistically significant difference due to method for %PROT (P = 0.13). Values for %BMCDXA were significantly (P < 0.0049) lower than %ASHCHEM values. The differences in body composition due to diet treatment were detected similarly by DXA and CHEM. Significant correlations were found between the methods (P < 0.0001) for %FAT (r = 0.99), %PROT (r = 0.96) and %BMC or ASH (r = 0.81). Bland-Altman plots showed good agreement between methods, and regression equations were developed to estimate CHEM values from DXA readings. DXA may provide an alternative method for assessing changes in whole body composition.

Adipose tissue expansion and the development of obesity: influence of dietary fat type.

Recent studies indicate that the prevalence of obesity in adults has increased by 30% or more in the past decade, with increases in both genders and in all ethnic and racial populations and age groups. Obesity is associated with many chronic diseases and alterations in physiologic function including cardiovascular disease, hypertension, diabetes mellitus, gallbladder disease and certain types of cancer. Much attention regarding dietary influences on obesity development or prevention has focused on high fat diets. Many studies have confirmed that high fat feeding leads to an expansion of adipose tissue mass through an increase in fat cell size and/or number and to the subsequent development of obesity. However, there is little definitive information on the effect of type of dietary fat, especially palm oil, on adipose tissue cellularity and the development of obesity. These studies were designed to determine whether dietary fat of different sources vary in their ability to produce obesity and to begin to elucidate the mechanism by which such divergence occurs. Male Osborne-Mendel rats were fed either a low fat (15% calories) or one of three high fat diets (65% calories) for 12 weeks. The predominant fat source in the high fat diets was either soybean oil, tallow, or palm-olein (a fraction of palm oil). Final body weight was not influenced by fat level or type; however, percent carcass lipid and fat pad weight were higher in soybean oil and tallow fed rats than in low fat and palm-olein fed rats. Fat pad specific increases in cell size and cell number were observed for tallow and soybean oil fed compared to low fat and palm-olein fed rats. Serum triglycerides were higher in the tallow and palm-olein fed rats compared to low fat fed rats; no significant effects of dietary fat type on serum cholesterol were observed. These results indicate that palm-olein, unlike tallow and soybean oil, were comparable to a low fat diet concerning fat pad weight, body composition and adipose tissue cellularity when fed for twelve weeks as 65% of energy intake. The lower fat storage in the palm-olein fed rats is perhaps associated with a slower rate of triglyceride uptake and/ or a reduced fat cell proliferative capacity. The influence of dietary fat type on the proliferative capacity of the pre-adipocytes and on the production of a local or systemic adipogenic factor is being determined in subsequent studies.