Consumption of a high-fat diet alters the homeostatic regulation of energy balance

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.     

Effects of diet composition on food intake and carcass composition in rats

Since most of the weight-reduced obese humans are in a protein deficit state, this study was designed to examine whether a high protein diet (HP) enhances the restoration of lean body mass and facilitates the maintenance of weight loss. Obesity in rats was produced by 16 weeks of high fat diet (HF) feeding. In the 17th week, all HF-fed obese rats were fed a limited amount of control diet to normalize their body weights, but they still had more body fat content. The HF-fed rats were then divided into subgroups with different diets offered for 5 weeks: HP, HF or chow diet. A control group was fed the chow diet throughout the study. HP feeding maintained normal body weight and carcass composition in weight-reduced obese rats by reducing feeding efficiency levels to within normal ranges. Weight-reduced rats fed a chow diet, however, had more fat mass than controls and HF feeding stimulated weight gain again. Therefore, a HP diet has a higher probability of enhancing weight loss maintenance in weight-reduced obese subjects than does a usual well-balanced diet.     

A “Western Diet” promotes symptoms of hepatic steatosis in spontaneously hypertensive rats

Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non‐alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to examine whether a high‐fat "Western" diet had effects on hypertension and associated NAFLD. Normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were placed on a normal chow or high‐fat diet for 8 weeks; blood pressure was measured fortnightly and body weight recorded weekly. As expected, SHR had elevated blood pressure compared to WKY. Diet did not influence blood pressure. Compared to SHR, WKY rats gained more weight, associating with increased white adipose tissue weight. Normotensive rats also had higher plasma cholesterol and triglycerides in response to a “Western” diet, with no changes in plasma glucose levels. Neither strain developed atherosclerosis. Interestingly, high‐fat diet‐fed SHR had increased liver weight, associating with a significant level of hepatic lipid accumulation not observed in WKY. Further, they exhibited hepatocellular ballooning and increased hepatic inflammation, indicative of steatohepatitis. These findings suggest that a high‐fat “Western” diet promotes features of NAFLD in SHR, but not WKY rats. Importantly, the high‐fat diet had no effect on blood pressure.     

微粒化非诺贝特对高脂饲养SHR脂毒性及胰岛素敏感性的影响

目的：观察微粒化非诺贝特对高脂饲养自发性高血压大鼠(SHR) 脂毒性及胰岛素敏感性（IS）的影响。方法:将27只SHR随机分为3组，1组给予标准饲料，其余2组分别给予高脂饲料、高脂饲料+非诺贝特100 mg·kg-1·d-1灌胃。3个月后，观察比目鱼肌细胞内脂滴沉积情况，计算脂质沉积指数（LAI）；进行葡萄糖耐量试验及游离脂肪酸测定。结果:(1) 与标准饲料组比较，高脂饲料组SHR体重和血浆甘油三酯（TG）、胆固醇（TC）水平明显增高，高密度脂蛋白胆固醇（HDL-C）水平明显降低(P＜0.05)，而非诺贝特治疗组与标准饲料组比较血压明显下降，HDL-C明显升高，体重、TG及TC水平无明显差异。(2) 高脂饲料组空腹血糖、游离脂肪酸、葡萄糖曲线下面积明显高于标准饲料组，胰岛素敏感指数显著低于标准饲料组（0.0038±0.0007 vs 0.0053±0.0013, P＜0.05）。非诺贝特组各项指标与标准饲料组无明显差异（P＞0.05）。(3)与标准饲料组相比，高脂饲料组比目鱼肌细胞内有大量脂质沉积（LAI: 6.42±0.59 vs 1.98±0.97, P＜0.05），非诺贝特治疗组比目鱼肌细胞内脂质含量显著减少，与标准饲料组无明显差别（LAI: 3.32±0.77 vs 1.98±0.97, P＞0.05）。经协方差分析排除血糖、血压因素影响后，上述差别仍有意义（F=10.46, P＜0.05）。（4） 骨骼肌脂质沉积指数与胰岛素敏感指数呈负相关（r=-0.58, P＜0.05），与TG、FFA、体重、葡萄糖曲线下面积呈正相关。结论:非诺贝特除了调脂外，还具有降低高脂饲养SHR体重、血压、脂毒性和改善胰岛素敏感性多重效应。     

小檗碱改善高脂饮食大鼠的胰岛素抵抗

目的:观察小檗碱是否能改善高脂饮食诱导的胰岛素抵抗,以探讨小檗碱干预糖耐量受损(IGT)的可能性。方法:8周龄雄性SD大鼠29只,分为正常组(NC,n=9)和高脂组(HF,n=20)。高脂饲料喂养14周后高脂组分为二组,10只大鼠继续喂养高脂饮食,另一小檗碱组(HF B,n=10)每天灌胃小檗碱150mg/kg体重,治疗6周后进行口服葡萄糖耐量试验和胰岛素耐量试验(ITT),评估小檗碱对胰岛素敏感性的影响。结果:HF组大鼠体重、肝重和附睾脂肪重量均明显高于HF B和NC组(均P<0.01),HF B组空腹血糖和葡萄糖负荷后2h血糖明显低于HF组(分别为5.70±0.52mmol/Lvs6.66±0.51mmol/L和7.88±0.46mmol/Lvs8.85±1.01mmol/L),空腹和葡萄糖负荷后2h胰岛素HF B组也显著低于HF组(分别为0.63±0.25ng/mlvs1.64±0.68ng/ml和1.20±0.21ng/mlvs3.60±0.36ng/ml)。各时间点血糖和胰岛素HF组均显著高于NC组(均P<0.01)。Homa胰岛素抵抗指数HF组明显高于HF B组(P<0.01)。ITT腹腔注射胰岛素后各时间点血糖下降幅度HF B组均高于HF组,15min时HF B组血糖下降23%,而HF组仅下降7%。结论:长期高脂饮食可导致大鼠胰岛素抵抗,小檗碱明显降低高脂大鼠的高胰岛素血症,改善胰岛素抵抗,因此适合于IGT的干预。     

Dietary fat content affects energy intake and weight gain independent of diet caloric density in rats

Recent considerations of high-fat diet hyperphagia have focused on fat's relatively high energy density as the critical variable which promotes overeating. However, a high-fat (HF) diet has been shown to enhance intake and weight gain relative to a high-carbohydrate (HC) diet when both energy density and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present studies investigated the generality of this finding across manipulations of diet caloric density, diet physical form, and chow availability. Separate groups of male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding enhanced weight gain relative to HC across both levels of energy density. HF hyperphagia also occurred when diets were presented in semisolid (gelled) form, and when chow was available in addition to liquid diet. These findings are consistent with previous observations that an HF diet can enhance daily kilocalorie intake and weight gain at least partly via a mechanism that is unrelated to caloric density.     

Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats

Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.     

Chronic stress, energy balance and adiposity in female rats

Stress preferentially increases the consumption of high fat foods in women, suggesting the interaction of these two factors may disproportionately predispose women toward excess weight gain. In the present study, female rats were exposed to a chronic high fat or chow diet and were exposed to 4 weeks of chronic variable stress (CVS) or served as home cage controls. Control females exposed to a high fat diet displayed many symptoms of the metabolic syndrome including increased body weight gain, total and visceral adiposity and insulin and leptin concentrations relative to all groups. However, CVS-high fat, CVS chow and control chow groups had similar body weight gain and caloric efficiency. This finding suggests that CVS increases energy expenditure much more in females exposed to a high fat diet relative to those fed a standard chow diet. The CVS-high fat group had increased adiposity and increased circulating leptin and insulin concentrations, despite the fact that their body weight did not differ from the controls. These results underscore the importance of assessing the degree of adiposity, rather than body weight alone, as an index of overall metabolic health. Overall, the data indicate that in female rats, chronic stress prevents high fat diet related increases in body weight, but does not prevent high fat diet induced increases in adiposity when compared to chow-fed females.     

Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet

Overconsumption and increased selection of high fat (HF) foods contribute to the development of common obesity. Because the hypothalamic melanocortin (MC) system plays an integral role in the regulation of food intake and dietary choice, we tested the hypothesis that proneness (-P) or resistance (-R) to dietary-induced obesity (DIO) may be due to differences in MC function. We found that prior to developing obesity and while still maintained on chow, acute, central administration of MTII, an MC agonist, produced a greater anorectic response in DIO-P rats than in DIO-R rats. However, after only 5 days of exclusive HF feeding, the DIO-R rats had significantly greater suppression of intake after MTII treatment than they did when maintained on chow. In addition, the DIO-P rats were much less responsive to MTII treatment than the DIO-R rats after only 5 days of the HF diet. In fact, MTII-induced anorexia during HF feeding correlated negatively with body weight gained on the HF diet. These results suggest that the voluntary decrease of HF feeding in DIO-R rats may be mediated by increased endogenous MC signaling, a signal likely compromised in DIO-P rats. Differences in MC regulation may also explain the observed preference for HF over a lower fat food choice in DIO-P rats. Finally, the results indicate that responses to exogenous MC challenge can be used to predict proneness or resistance to DIO.     

Effects of alternations (10 days) of high-fat with normal diet on liver lipid infiltration, fat gain, and plasma metabolic profile in rats

The purpose of the present study was to test the hypothesis that short-term alternations of high-fat with normal chow feeding result in higher fat accumulation in liver than continuous intake of the same high-fat diet. Male Sprague-Dawley rats (7 weeks of age) were divided into 3 groups according to diet composition: standard chow (SD; 12,5% kcal as fat), high-fat (HF; 42% kcal as fat), and food cycles (FC) consisting of 10-day alternations between HF and SD diets beginning with the high-fat diet. Rats in each of these 3 groups were sacrificed after 10, 30, and 50 days (n = 10 rats/sub-groups). Energy intake, body weight, liver and muscle relative weights were not significantly (P > 0.05) different between FC- and HF-fed rats. Using the total energy intake for the 50-day period, it was calculated that approximately 30% less calories as fat was ingested in the FC- compared to the HF-fed rats. In spite of this, liver lipid infiltration as well as fat accretion in abdominal adipose tissues were increased (P < 0.01) similarly in FC- and HF-fed rats. Plasma FFA and insulin levels depicted strong tendencies (P < 0.07) to be higher in FC- than in continuous HF-fed rats at the end of the 50-day period. These results indicate that, despite a 30% reduction in ingested lipids, alternations of HF with normal chow diet compared to the continuous hyperlipidic diet caused the same level of infiltration of lipids in the liver and in the abdominal adipose tissues and, to a certain extent, may even result in a larger deterioration of the metabolic profile.     

Post weaning high fat feeding affects rats' behavior and hypothalamic pituitary adrenal axis at the onset of puberty in a sexually dimorphic manner

Feeding adult rats with high fat (HF) diets can alter their hypothalamic pituitary adrenal (HPA) axis responsiveness. In the present study, we examined the effect of a high fat diet, applied in rats from weaning to puberty, on their behavior and HPA axis status at puberty onset. Wistar rats of both sexes were fed postweaning with two diets containing either 24% fat (high fat, HF) or 4.3% fat (normal chow) by weight. HF enhanced puberty onset in female rats, without increasing body weight gain in either sex, compared with chow-fed animals. In the forced swim test, HF males exhibited a more active behavioral response on the first day, whereas HF females a more passive response during the second day of the test, as compared with their chow-fed counterparts. In the open field test, HF females showed increased sniffing but reduced rearing, compared with chow-fed females and were less explorative than HF males in the central arena. All animals could learn and recall a water maze task though HF males spent more time in the opposite quadrant than chow-fed males during memory test. The HPA axis status of these animals was investigated under basal conditions. Pubertal fat-fed males had lighter adrenals, while females heavier ones, compared with their counterparts. In addition, plasma corticosterone levels of female rats were increased and glucocorticoid receptor levels in their hypothalamus were reduced due to fat diet, while in males no such changes were detected. We conclude that HF feeding during the prepubertal period can affect behavior and the HPA axis of rats at puberty onset, well before the appearance of the obese state, in a sexually dimorphic manner. Fat diet impacted more the female HPA axis, suggesting that their system is more sensitive to fat-induced nutritional imbalance during adolescence. Present data suggest that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction that in turn may trigger the appearance of stress-related disorders during adolescence.     

Dietary fat-induced hyperphagia in rats as a function of fat type and physical form

The influence of dietary fat on food intake and weight gain was assessed by feeding adult female rats diets that differed in the type and form of fat, as well as in the availability of other macro- and micronutrients. Compared to chow-fed controls, the various fat diets increased total food intake by 4% to 27%. Specifically, rats fed chow and a separate source of fat (fat option diet) consumed more fat and total calories, and gained more weight when the fat source was emulsified corn oil rather than pure corn oil or was vegetable shortening rather than corn oil. However, corn oil and shortening had similar effects on caloric intake and weight gain when presented as emulsified gels. Also, pure and emulsified-gel forms of shortening did not differ in their effects on caloric intake and weight gain. Supplementing the vegetable shortening with micronutrients, however, enhanced its hyperphagia-promoting effect. The results of two-choice tests revealed that the rats' preferences for the orosensory properties of the various fat sources did not account for the differential hyperphagias obtained. Rather, it appears that long-term fat selection and caloric intake are influenced primarily by postingestive factors. Fat selection and total intake were determined not only by the fat source itself, but also by the other diet options. That is, rats selected more fat and consumed more calories when chow was the alternative food than when separate sources of carbohydrate and protein were available.     

Dietary self-selection vs. complete diet: body weight gain and meal pattern in rats.

Food intake and body weight gain of male adult Wistar rats were examined in two groups of animals. One group (n = 14) was allowed to select its diet from separate sources of protein (casein, 3.1 kcal/g), fat (lard and sunflower oil, 7.9 kcal/g) and carbohydrate (CHO, starch and sucrose, 3.3 kcal/g). Another group (n = 10) received a nutritionally complete diet (3.3 kcal/g). After 2 weeks of adaptation to the diets, body weights and meal patterns were recorded for at least 4 days. The total caloric intake was nearly identical for the two groups of rats. Rats given dietary choice gained less weight over 4 days than rats fed chow and showed reduced feed efficiency. During the 24-h period, self-selecting rats consumed 20.8% of calories as proteins, 21% as fats and 58.2% as CHO. Self-selecting rats ate significantly less calories during the day than did rats given chow. The chow diet consisting of 17.3% calories as protein, 7.6% as fat and 75.1% as CHO. When comparing the self-selecting group nutrient intakes to those of chow-fed group it was observed that 24-h protein calorie intakes were identical in both groups. Fat intake was significantly higher and CHO reduced as compared to chow-fed rats. During the day, CHO intake was higher in self-selecting rats, and fat intake was not significantly reduced. During the night, protein and fat intakes were significantly higher in self-selecting rats, while CHO intake was significantly decreased, particularly in the last periods of the night.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feeding studies in weanling rats with dorsomedial hypothalamic lesions: maintenance of competence to compensate for additional calories.

Weanling rats received bilateral electrolytic lesions in the dorsomedial hypothalamus primarily destroying the dorsomedial hypothalamic nuclei (DMN). Sham-operated rats served as controls. After a 14 day postoperative period during which food intake (lab chow) and body weight were recorded, each of the above groups were subdivided into 2 groups. One DMN group and one sham-operated control group were continued on lab chow alone throughout the remainder of the study. The other DMN group and the second control group were given additional calories in the form of a liquid diet by stomach tube during 2 separate periods of 10 and 14 days, respectivly, to increase their caloric intake beyond that taken in spontaneously. Both tube-fed groups reduced their ad lib caloric intake from chow considerably and to the same extent. Body weight gains were similar in tube-fed versus non-tube-fed rats, whether with or without DMN lesions. After the second, 14-day-long tube feeding period, however, DMN rats regulated their body weight somewhat less precisely than the controls. This may be related to their reduced food intake during that time period. The data indicate that weanling rats with DMN lesions, despite their basic hypophagia, do not show a deficit in caloric metering and gross body weight regulation.     

Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin

Obesity results in the increased secretion of various hormones controlling food intake and body weight, such as leptin, and insulin; increased circulating levels of pancreatic amylin have also been described in obese humans and rodents. Because leptin-resistance is present in diet-induced obese (DIO) rats, and because hyperleptinemia seems necessary for the full development of leptin resistance, we tested whether amylin sensitivity is inversely correlated with adiposity, such that DIO reduces the anorectic action of acute amylin. We also determined if hyperamylinemia leads to a change in amylin sensitivity. In the first experiment, rats were chronically exposed to a high fat (HF; 60% fat) diet or fed standard chow for control. The anorectic response to amylin was tested on several occasions over a 14 week observation period. HF feeding led to the expected increase in body adiposity; the response to an acute amylin injection (5 - 50 μg/kg s.c.) was unaltered for 10 weeks of HF feeding. Even after 12 weeks on a HF diet, which clearly caused obesity, acute administration of amylin (5 μg/kg, s.c.) was still able to suppress food intake, although the suppression was not statistically significant. Further experiments using additional doses of amylin will be necessary to demonstrate possible amylin resistance after HF feeding or in DIO rats. In the second experiment, we tested more specifically whether hyperamylinemia that may result from HF feeding and subsequent obesity, reduces the sensitivity of the amylin signaling system. To avoid confounding factors, we chronically infused lean chow fed rats with amylin (5 or 10 μg/kg/day s.c.) to elevate their plasma amylin concentration to levels observed in obese rats (30 - 40 pM). In the absence of obesity, hyperamylinemia did not lead to a reduced sensitivity to acute amylin (5 - 20 μg/kg s.c.) injections; acute amylin reduced eating similarly in all groups of rats. Overall, we concluded that direct diet effects by short term exposure to HF appear to be of little importance for amylin sensitivity; further, long-term maintenance on a HF diet and the resulting obesity only slightly attenuated the anorectic response to acute amylin. Because we observed no marked changes in amylin sensitivity in lean, chow fed rats with induced hyperamylinemia, amylin receptor downregulation in chronic hyperamylinemia does not seem to occur.     

Diverse basal and stress-related phenotypes of Sprague Dawley rats from three vendors

Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences and a metabolic feedback hypothesis of hypothalamo-pituitary-adrenal (HPA) regulation. Charles River and Harlan rats gained weight faster than Simonsen rats, but chow intake standardized for body weight was not increased, consistent with their greater caloric efficiency. Weight gain was inversely related with mean daily temperatures, without differences in activity levels. Half of the animals given lard and 32% sucrose solutions in addition to chow increased caloric intake and core temperature, decreased caloric efficiency, and increased fat depots, leptin, and in Simonsen rats, insulin. A 5-day regimen of once-daily 2-h restraint decreased feeding and caloric efficiency. Rats from two vendors with the availability of sucrose and lard, Charles River and Simonsen, showed blunted HPA responses to restraint compared to chow controls, whereas the Harlans exhibited no adrenocorticotropin (ACTH) response and an amplified adrenocortical response on the high-energy diet compared to chow controls. Substantial phenotypic differences exist between Sprague Dawley rats from different vendors with respect to metabolism and HPA function. The metabolic feedback hypothesis was supported in two of the three vendors' rats.     

High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake

Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.     

Consumption of a high-fat diet induces central insulin resistance independent of adiposity

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.     

高脂饮食诱发血糖升高的动物模型中瘦素与胰岛素变化的关系

高脂饲料喂养大鼠,诱发胰岛素抵抗形成血糖升高,以研究瘦素与糖尿病的关系。将大鼠分为正常和高脂饲料喂养组,于喂养前及喂养30、60d时测血糖、瘦素与胰岛素水平,行高胰岛素正常血糖钳夹试验,最后分离分离脂肪称重。结果：高脂饮食组具有明显的胰岛素抵抗,有50％血糖升至8．3mmol/L以上;形成糖尿病的大鼠体重与对照组无明显区别;高脂饮食组瘦素与胰岛素水平与对照组比较有明显差异;所有大鼠瘦素水平与体重、胰岛素、血糖均呈正相关。结论：（1）高脂饮食是导致胰岛素抵抗形成糖尿病的诱因之一;（2）体脂含量与糖尿病正相关;（3）瘦素抵抗与胰岛素抵抗形成糖尿病的发病机制可能有关;（4）瘦素水平随着鼠龄的增加而增高,且参与体重的调节。     

Effects of estradiol on food intake and meal patterns for diets that differ in flavor and fat content

Apart from the well known inhibitory effects of estradiol on food intake, meal size, and body weight in female rats that have been documented over the past thirty years, a more recent report presents the opposite finding; that a large dose of estradiol can increase food intake and weight gain in gonadally intact female rats presented with a palatable diet. The purpose of the present experiment was to further examine this hypothesis by evaluating the ability of estradiol to influence feeding behavior in ovariectomized rats presented with diets that differ in flavor and fat content. Female rats were given a cyclic regimen of estradiol benzoate treatment (5.0 or 20.0 µg) or the oil vehicle and were presented with the standard chow diet or a diet with a higher fat content and chocolate flavor. Food intake, meal size, and meal number were monitored three days after the first injection of estradiol or oil. Compared to the chow diet, food intake increased when animals had access to the chocolate/fat diet during the vehicle treatment condition. Both doses of estradiol significantly decreased food intake, meal size, and body weight gain when animals were presented with either the standard chow diet or the chocolate/fat diet. These findings indicate that estradiol does not stimulate the intake of a palatable diet in ovariectomized rats, and suggest that previous results showing that estradiol enhanced eating and weight gain stemmed from a disruption of the hypothalamic-pituitary-gonadal axis when intact females received a large dose of exogenous estradiol.