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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects of peripherally administered pyruvate and lactate on the intake of high fat (HF) and low fat (LF) diets by a strain of rat either sensitive (Osborne-Mendel, OM) or resistant (SSB/Pl) to high fat-induced obesity. Both pyruvate and lactate inhibited the intake of HF and LF diets by OM rats and these effects were blocked by selective hepatic vagotomy. In contrast, in S5B/Pl rats fed an LF diet the responses to pyruvate and lactate were attenuated and were absent in S5B/Pl rats fed the HF diet. These data suggest that OM and S5B/Pl rats differ either in their metabolism of pyruvate and lactate or in their responses to these metabolites.
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PMID:Effects of pyruvate and lactate on food intake in rat strains sensitive and resistant to dietary obesity. 870 Sep 60

This study compared the effects of exogenous pyruvate and lactate on the serum levels of pyruvate, lactate, glucose, alanine, and insulin, as well as the activity of hepatic pyruvate dehydrogenase (PDH) in strains of rat that were either sensitive [Osborne-Mendel (OM)] or resistant (S5B/Pl) to high-fat diet-induced obesity. Serum pyruvate and lactate were significantly higher and glucose lower in ad libitum-fed OM rats, but these differences disappeared after an 18-h fast. The increase in pyruvate and lactate after exogenous pyruvate administration was significantly greater in S5B/Pl rats than OM rats. There were no differences in serum alanine with strain or diet. The total PDH activity was similar across strains and diets but the proportion of PDH in its activated form (PDHa) was decreased in ad libitum-fed S5B/Pl rats. Pyruvate injection increased insulin and hepatic PDHa activity in OM rats fed both high- and low-fat diets, but these responses were greatly attenuated or absent in S5B/Pl rats. The data are consistent with the hypothesis that modulation of carbohydrate oxidation by PDH may be related to susceptibility to obesity when rats are fed a high-fat diet.
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PMID:Pyruvate and hepatic pyruvate dehydrogenase levels in rat strains sensitive and resistant to dietary obesity. 878 Feb 12

We have investigated the central effect of a kappa-opioid agonist and an antagonist on the macronutrient preference in two strains of rat, the Osborne Mendel (OM) and S5B/P1 rats, that have different susceptibility to obesity and differential preference for dietary fat intake. OM rats prefer diets high in fat and are sensitive to diet-induced obesity, whereas S5B/P1 prefer a low fat diet and are resistant to high-fat diet-induced obesity. Rats adapted to a two-choice high fat (HF)/low fat (LF) diet were food deprived (20 h) and then infused into the third cerebroventricle with 10 micrograms nor-binaltorphimine (nor-BNI), a selective kappa-antagonist. Nor-BNI preferentially suppressed HF intake, but not LF intake in OM rats, whereas it affected neither diet in S5B rats. Infusion of U50488, a selective kappa-agonist (33 nmol), into the third cerebroventricle in sated rats, potently stimulated the intake of HF only in the OM rats, whereas it induced a significant but moderate stimulation of intake of both HF and LF diets in the S5B/P1 rats. Total energy intake following U50488 was not significantly different between the two strains. These findings suggest that the enhanced sensitivity of the OM rats to kappa-opioid stimulation for dietary fat may contribute to their preference for dietary fat and possibly their increased susceptibility for obesity.
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PMID:Differential response to kappa-opioidergic agents in dietary fat selection between Osborne-Mendel and S5B/P1 rats. 943 46

The purpose of this experiment was to determine if Osborne-Mendel (OM) rats, which are susceptible to dietary-induced obesity, and S5B/PL (S5B) rats, which are resistant to dietary-induced obesity, differ in their feeding responses to mercaptoacetate (MA), which blocks fatty acid oxidation, or 2-deoxy-D-glucose (2DG), which blocks glucose utilization. 2DG (100 mg/kg or 200 mg/kg) increased food intake in both strains of rats on a high-fat diet (56% energy from fat). Mercaptoacetate (600 mumol/kg) increased food intake in OM but not S5B rats on a high-fat diet. When maintained on a low-fat diet (10% energy from fat), MA (400 mumol/kg or 600 mumol/kg) stimulated food intake in OM rats, whereas S5B rats increased food intake only after the highest dose of MA (600 mumol/kg). MA stimulated carbohydrate and protein intake in OM rats maintained on a macronutrient selection diet, whereas S5B rats maintained on this diet did not significantly increase intake of any macronutrient after MA. These results demonstrate that OM and S5B rats have a similar food intake response to 2DG but a dissimilar response to MA. The variable response to MA in these strains may be due to a difference in peripheral or central signaling systems related to fatty acid oxidation or a difference in metabolic environments between the strains, which in turn affects the feeding response to MA. These studies suggest that a difference in control of fatty acid oxidation may account for the difference in susceptibility to obesity when eating a high-fat diet.
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PMID:Feeding response to mercaptoacetate in Osborne-Mendel and S5B/PL rats. 944 44

Osborne-Mendel (OM) and S5B/Pl rats differ in their sensitivity to develop obesity when fed a high fat (HF) diet; OM rats become obese, whereas S5B/Pl rats remain thin. We have investigated the possibilities that either an impaired leptin response or resistance to leptin action underlies the sensitivity to this form of obesity in OM rats. In Experiment 1, OM and S5B/Pl rats fed a nonpurified diet were killed at d 0 or were fed either a HF (56% fat energy) or a low fat (LF, 10% fat energy) diet for 2 or 7 d. The HF diet increased serum leptin significantly by d 2 to levels that were similar in both rat strains. At 7 d, leptin levels were lower than at d 2 but remained higher than levels in the d 0 control groups. The leptin mRNA:18S RNA ratio in epididymal adipose tissue increased to higher levels in HF-fed OM rats than in S5B/Pl rats fed that diet. However, although the LF diet had no effect in S5B/Pl rats, it increased leptin mRNA levels in epididymal adipose tissue of OM rats compared with the controls fed the nonpurified diet. In Experiment 2, OM and S5B/Pl rats were fed HF or LF diets for 5 wk. At that time, their feeding response to a range of leptin doses (0, 1, 5 or 10 microgram) given intracerebroventricularly was tested after overnight food deprivation. There was a similar dose-dependent reduction in energy intake in response to leptin in both OM and S5B/Pl rats. These responses were independent of the diet. The data suggest that the susceptibility of OM rats to HF diet-induced obesity is not related to either a loss of central sensitivity to leptin or a failure to enhance leptin production acutely, although the failure to maintain chronically increased levels of serum leptin could contribute to the obesity.
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PMID:The effects of a high fat diet on leptin mRNA, serum leptin and the response to leptin are not altered in a rat strain susceptible to high fat diet-induced obesity. 977 25

We previously demonstrated that taste receptor cells (TRCs) respond to cis-polyunsaturated fatty acids (PUFAs) through an inhibition of delayed rectifying K channels (KDR), which may represent the transduction mechanism for dietary fat. To determine if there is a link between the sensitivity of fungiform TRCs to PUFAs and dietary fat preferences, we compared the PUFA-sensitivity of TRCs using patch clamp techniques from Osborne-Mendel (O-M) and S5B/Pl rats, which display dietary preferences for fat over carbohydrate and carbohydrate over fat, respectively. In isolated TRCs, the PUFAs, linoleic (C18:2), linolenic (C18:3) and arachidonic acid (C20:4) inhibit KDR in a concentration-dependent manner in both strains, while the unsaturated lauric acid (C12:0) was ineffective. KDR from TRCs of S5B/Pl rats were significantly more sensitive to inhibition by all three PUFAs (10 microM) than were TRCs from O-M rats. We are currently investigating whether this differential responsiveness is due to (i) the relative affinity of the interaction between cis-PUFAs and the delayed rectifying K channels or (ii) the relative density of delayed rectifying K channels in the two rat strains. Whatever the mechanism, these data suggest an inverse correlation between peripheral gustatory sensitivity to PUFAs and the dietary preference for fat. This finding may provide insight into the mechanism for sensing dietary fat that allows the S5B rats to reduce fat intake on a high-fat diet and avoid the obesity which results when O-M rats eat a high-fat diet.
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PMID:Dietary fat preferences are inversely correlated with peripheral gustatory fatty acid sensitivity. 992 99

The effects of duodenal infusions of fats on sham feeding was measured in two strains of rats that differ in their susceptibility to fat-induced obesity. Osborne-Mendel rats are prone to developing obesity on a high-fat diet and preferentially choose fats over carbohydrates in macronutrient selection paradigms. In contrast, S 5B/PL rats are resistant to developing obesity when eating a high-fat diet, and preferentially choose carbohydrates in macronutrient selection paradigms. To test the hypothesis that differences in the satiating potency of fats in the small intestine contributed to these differences between the two strains, we measured the effects of duodenal infusions of Intralipid and sodium linoleate on sham-feeding intakes. The results were consistent with the hypothesis. Duodenal infusions of either of these fats decreased intake significantly more in S5B/PL rats than in Osborne-Mendel rats. Both rat strains sham fed similar amounts when intestinally infused with 0.15 M NaCl. These results suggest that differences in responses to intestinal satiating mechanisms may contribute to the differences in susceptibility to fat-induced obesity in these rat strains.
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PMID:Differential satiating effects of fats in the small intestine of obesity-resistant and obesity-prone rats. 1038 6

Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high-fat diet.
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PMID:Acute changes in the response to peripheral leptin with alteration in the diet composition. 1120 81

This study examined the cardiovascular, renal, and hormonal responses of dietary-induced obesity in Osborne-Mendel (OM) rats. Male OM rats were fed either a low (LF; n = 10)- or high-fat (HF; n = 11) diet for 17 wk. During week 15 of the study, arterial pressure was measured directly, 24 h/day, from chronically indwelling catheters. Body and kidney weights were 46 +/- 5 and 33 +/- 5% greater, respectively, in rats fed HF vs. LF diet. Left and right ventricular weights were also greater in rats fed HF diet (21 +/- 7 and 36 +/- 6%, respectively). Direct measurement of arterial pressure revealed only a slight increase in mean arterial pressure (88 +/- 1 in rats fed HF diet vs. 85 +/- 1 mmHg in rats fed LF diet), whereas there was no difference in resting heart rate between the two groups. Consumption of HF diet was also associated with a 3.5-fold increase in plasma insulin, a 16 +/- 4% higher blood glucose, and a 40 +/- 6% reduction in plasma renin activity compared with LF-fed rats. Thus feeding OM rats HF diet led to obesity, cardiac and renal hypertrophy, and hyperinsulinemia but only a slight increase in mean arterial pressure.
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PMID:Cardiovascular and renal responses to a high-fat diet in Osborne-Mendel rats. 1144 59

Ghrelin is a peptide produced by the stomach and released into the circulation. As a natural ligand of the growth hormone secretagogue (GHS) receptor, it stimulates growth hormone secretion but it also stimulates feeding in humans and rodents. The orexigenic effect of ghrelin has been related to AgRP/NPY and orexin pathways. We proposed that ghrelin might be involved in the susceptibility to diet induced obesity and in the regulation of macronutrient selection. We have investigated these hypotheses in two strains of rat, the Osborne-Mendel (OM) rat that prefers diets high in fat and is sensitive to dietary obesity and the S5B/P1 (S5B) rat that prefers a low fat diet and is resistant to high fat diet induced obesity. OM and S5B rats were adapted to a choice of high fat (HF) and low fat (LF) diet for 2 weeks. GHRP-2, an analogue of ghrelin, was injected intraperitoneally into satiated and 24 h fasted rats at doses of 10, 30 and 90 nmol. Food intake was measured over the next 4 h period. In satiated S5B rats, GHRP-2 stimulated intake of the LF diet in a dose dependent manner but did not affect the intake of the HF diet. In satiated OM rats, 90 nmol of GHRP-2 stimulated HF intake. In contrast, neither fasted OM nor S5B rats increased the intake of either HF or LF diet in response to GHRP-2. Fasting for 18 h induced a large rise in ghrelin mRNA in stomach of OM rats but not in S5B rats. There were no significant differences in plasma total ghrelin. An increase in ghrelin mRNA in stomach immediately before the onset of the dark cycle was observed in OM but not in S5B rats. Active ghrelin level was significantly affected by different feeding conditions in both OM and S5B rats adapted on HF diet with a trend to increase after 48 h of fasting and to decline to basal levels following 10 h of refeeding. These data suggest that ghrelin stimulates the intake of the preferred macronutrient. In addition, a differential regulation of ghrelin gene expression between OM and S5B rats may be important in their differential sensitivity to HF diet-induced obesity.
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PMID:Regulation of ghrelin gene expression in stomach and feeding response to a ghrelin analogue in two strains of rats. 1557 7


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