Modulation of N-nitrosomethylurea induced mammary tumorigenesis by dietary fat and voluntary exercise.

The effect of dietary fat and exercise on N-nitrosomethylurea [NMU:CAS:684-93-5]-induced mammary tumorigenesis in female F344 rats was investigated. Rats were fed the NIH-07 diet until NMU administration on day 50 of age, when they were transferred to four treatment groups. Three sedentary groups were fed either high-fat (20% wt/wt), medium fat (10%) or low fat (5%) diets (HF, MF, LF, respectively), and a fourth group was fed a HF diet but allowed free access to an activity wheel (HFEX). Tumor yields among the three sedentary groups were significantly greater in the HF and MF groups when compared to the LF group. Voluntary exercise reduced tumor yields and delayed time of tumor appearance in HFEX animals to levels similar to those found in LF sedentary animals. Animals with voluntary access to exercise wheels averaged between 1.03 and 2.85 miles/day, consumed more food (+ 18%) and exhibited greater weight gain (+ 13%) than their sedentary counterparts. No differences in weight gains were detected among the HF, MF, and LF groups, despite widely varying amounts of fat intake. Body composition studies indicated that body fat content was not influenced by the quantity of fat consumed in the diet, but was significantly reduced by voluntary exercise (-20%). Since exercise and fat intake have been associated with alterations in endocrine status, circulating bioactive and immunoactive prolactin were assessed at termination. No significant changes were found in either form of prolactin among the four experimental groups, casting doubt on mediation by this pituitary hormone.     

Ethanol feeding stimulates trichloromethyl radical formation from carbon tetrachloride in liver

1. Female, Sprague-Dawley rats were fed liquid ethanol or control diets, both of which contained fat either at 35% (high fat, HF) or 12% (low fat, LF) of total calories. The rats were given an oral dose of 13CCl4 along with the spin trapping agent, phenyl tert.-butyl-nitrone (PBN). 2. Analysis of the hepatic lipid extracts revealed a signal due to the trichloromethyl radical (CCl3) adduct of PBN. Ethanol feeding in the HF diet increased the signal intensity two-fold over controls, whereas ethanol feeding in the LF diet caused only a 35% increase. 3. In isolated microsomes, ethanol feeding in HF or LF diets increased CCl3 formation by approx. 8-fold and 4-fold, respectively, over control values. These data support the hypothesis that ethanol induces a cytochrome P-450 isozyme that is highly active in the metabolism of CCl4 to the CCl3 radical. 4. Ethanol feeding markedly enhanced the hepatotoxicity of CCl4; however, there were no differences in the loss of hepatic enzymes into blood between the ethanol plus HF or ethanol plus LF groups. Thus, ethanol is likely to increase CCl4 toxicity by some mechanism in addition to increased trichloromethyl radical formation.     

高脂诱导性肥胖大鼠的胰岛素敏感性与TNF-α及FFAs水平

目的观察正常大鼠在高脂饮食诱导下形成肥胖后的胰岛素敏感性及其TNF-α、FFAs的变化。方法9周龄健康雄性Wistar大鼠16只,随机分为正常饲养组(NC熏n=8)和高脂饲养组(HF熏n=8)。喂养10周,比较两组大鼠体重、胰岛素抵抗指数(HOMA-IR)、以及TNF-α、FFAs等的变化。结果经10周高脂喂养,HF组与NC组比较,体重和内脏脂肪组织显著增加(HF组大鼠体重较NC组增加了11.4%,P<0.05;HF组大鼠内脏脂肪组织较NC组增加了20.7%,P<0.01),并出现胰岛素抵抗(HOMA-IR:HF组为8.88±4.25,NC组为3.92±2.26熏P<0.05),空腹FFAs和TNF-α水平显著上升,较NC组分别增加了80.8%(P<0.05)和58.4%(P<0.05),但两组空腹血糖差异无显著性(HF组为7.89±1.46mmol/L,NC组为8.70±1.59mmol/L熏P>0.05)。结论高脂饮食可诱导大鼠肥胖伴胰岛素抵抗,其胰岛素抵抗的形成可能与TNFα、FFAs水平的升高有关。     

Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.     

Metabolic disorders and oxidative stress programming in offspring of rats fed a high-fat diet during lactation: effects of a vinifera grape skin (ACH09) extract

This study examined the effect of Vitis vinifera grape skin ACH09 extract (ACH09) on metabolic disorders and oxidative stress in adult offspring of rats fed a high-fat diet (HF) during lactation. Four groups of female rats were fed: control diet (7% fat); ACH09 (7% fat + 200 mg·kg·d ACH09 orally); HF (24% fat); HF+ ACH09 (24% fat + 200 mg·kg·d ACH09 orally) during lactation. From weaning onward, all female offspring were fed a control diet and killed when they were 90 or 180 days old. Systolic blood pressure was increased in adult offspring of HF-fed dams, and ACH09 prevented hypertension. Increased adiposity, plasma triglyceride, glucose levels, and insulin resistance were observed in offspring from both ages, and these changes were reversed by ACH09. The plasma oxidative damage assessed by malondialdehyde levels was increased, and nitrite levels decreased in the HF group of both ages, which were reversed by ACH09. In addition, ACH09 restored the decreased plasma and mesenteric artery antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in the HF group. In conclusion, ACH09 protected normally fed offspring of HF-fed dams during lactation from phenotypic and metabolic characteristics of metabolic syndrome providing an alternative nutritional resource for the prevention of metabolic syndrome.     

Dampened Mesolimbic Dopamine Function and Signaling by Saturated but not Monounsaturated Dietary Lipids

Overconsumption of dietary fat is increasingly linked with motivational and emotional impairments. Human and animal studies demonstrate associations between obesity and blunted reward function at the behavioral and neural level, but it is unclear to what degree such changes are a consequence of an obese state and whether they are contingent on dietary lipid class. We sought to determine the impact of prolonged ad libitum intake of diets rich in saturated or monounsaturated fat, separate from metabolic signals associated with increased adiposity, on dopamine (DA)-dependent behaviors and to identify pertinent signaling changes in the nucleus accumbens (NAc). Male rats fed a saturated (palm oil), but not an isocaloric monounsaturated (olive oil), high-fat diet exhibited decreased sensitivity to the rewarding (place preference) and locomotor-sensitizing effects of amphetamine as compared with low-fat diet controls. Blunted amphetamine action by saturated high-fat feeding was entirely independent of caloric intake, weight gain, and plasma levels of leptin, insulin, and glucose and was accompanied by biochemical and behavioral evidence of reduced D1R signaling in the NAc. Saturated high-fat feeding was also tied to protein markers of increased AMPA receptor-mediated plasticity and decreased DA transporter expression in the NAc but not to alterations in DA turnover and biosynthesis. Collectively, the results suggest that intake of saturated lipids can suppress DA signaling apart from increases in body weight and adiposity-related signals known to affect mesolimbic DA function, in part by diminishing D1 receptor signaling, and that equivalent intake of monounsaturated dietary fat protects against such changes.     

Serum resistin is not associated with obesity or insulin resistance in humans

BACKGROUND: Resistin has proposed link with obesity related insulin resistance and type 2 diabetes. The physiologic role of resistin in humans remains unknown. It is suggested that circulating resistin levels are not associated with obesity or insulin resistance in humans. However, the effects of weight loss on serum resistin concentration has not been studied. In order to better understand the physiologic role of resistin in human obesity, we measured the serum resistin concentration in subjects with severe obesity (before and after 6-months of dietary intervention) to test the hypothesis that serum resistin concentrations are elevated amongst individuals with severe obesity and weight loss would reduce these levels. METHODS: Seventy-one obese subjects (defined as BMI > 35 kg/m2) who were randomized to low fat (LF) vs low carbohydrates (LC) diets and who completed the 6-month follow-up were studied. Their baseline demographic information was collected and serum resistin, insulin, glucose were measured at baseline and at 6-months. RESULTS: Subjects in LC diet lost more weight than LF (-19.54 +/- 7.87 lbs vs -7.83 +/- 11.23 lbs., p = 0.001). Insulin sensitivity (HOMA) improved in LC group compared with LF group [-3.72 +/- 9.84 (LC) vs +1.31 +/- 7.31 (LF), p = 0.006]. Serum resistin levels did not decrease in either diet. CONCLUSIONS: Our study found that despite a significant weight loss and improvement in insulin sensitivity there was no reduction in serum resistin concentration in morbidly obese men with metabolic syndrome suggesting that resistin does not play a central role in obesity related insulin resistance.     

The long-term effect of dietary administration of refined sugars and sugar alcohols on plasma biochemistry, urine biochemistry and tissue histology in mice given a limited degree of dietary self-selection

A prototype animal feeding model is described in which mice were meal-fed a balanced diet but were given free access to water (controls) or 20% (w/v) solutions of glucose, sucrose, fructose, xylitol or sorbitol. Under these conditions it was found that the provision of an alternative energy source, in the form of a refined carbohydrate, produced marked effects on total energy intake, mouse cube (i.e. balanced energy) intake and body weight. There were also changes in the metabolic states of the animals as assessed by serum levels of glucose, urea and cholesterol, plasma levels of lactate and D-3-hydroxybutyrate, and urinary excretion of urea and oxalate. Histological examinations of tissue indicated that the sucrose-fed mice had a tendency to suffer from acute congestion of the lungs and liver steatosis. Given a limited degree of dietary self-selection it appears that mice are more likely to be at risk of excessive food consumption and obesity when given glucose- or sucrose-containing diets than they are when fructose-, xylitol- or sorbitol-containing diets are given.     

Effects of benidipine hydrochloride on autonomic nervous activity in hypertensive patients with high- and low-salt diets

The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.     

Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in obese subjects

The effects of simple carbohydrates on erythrocyte insulin receptors, plasma insulin and plasma glucose were studied during four hypocaloric, hyperproteic, diets. One diet contained no carbohydrate; the other three contained 36 g of either glucose, galactose or fructose. These diets were given for a 14-day period to groups of moderately obese subjects. The hypocaloric carbohydrate-free diet produced a decrease in plasma insulin and glucose concentrations concomitant with an increase in the number of insulin receptors. A similar increase in insulin receptor number was found when the diet was supplemented with glucose or galactose, but not with fructose. The presence of fructose in the diet prevented any increase in insulin receptor number.     

The effects of morphine on diet selection are dependent upon baseline diet preferences

It has been reported that morphine causes a selective increase in the intake of dietary fat. Because we have noted considerable variability among rats in their preferences for carbohydrate and fat, we reasoned that the effect of morphine on diet selection may differ in fat-preferring vs. carbohydrate-preferring rats. Male Sprague-Dawley rats were given ad lib access to separate sources of carbohydrate, fat and protein (Experiment 1), or to a carbohydrate/protein and a fat/protein diet (Experiment 2). After daily baseline intakes of the diets were determined, all rats were tested for feeding responses to subcutaneous injections of morphine (0, 2 and 10 mg/kg). Significant positive correlations were found between baseline daily intake of a given diet and the effect of morphine on the intake of that diet. Generally, morphine increased carbohydrate intake in carbohydrate-preferring rats, and increased fat intake in fat-preferring rats. These results suggest that the effect of morphine is to increase intake of a preferred diet rather than to increase intake of a specific macronutrient.     

7-OH-DPAT selectively reduces intake of both chow and high fat diets in different food intake regimens

Mesolimbic dopaminergic system activation correlates with ingestive behavior in numerous feeding regimens. DA release is enhanced by food intake following deprivation, amount of food consumed, and the palatability of the food consumed. The dopamine-3 receptor (D3-R) has a limited expression pattern that is restricted largely to the mesolimbic dopaminergic system. The D3-R has been hypothesized to inhibit DA-mediated reward, locomotion and motivation. To test the potential for an inhibitory role of the D3-R on food intake, we administered the D3-R agonist 7-OH-DPAT (5, 10 and 50 microg/kg ip) to rats that had ad libitum access to standard rodent chow (3.41 kcal/gm, 0.51 kcal/gm from fat) or a preferable, high fat (HF) (4.4 kcal/gm, 1.71 kcal/gm from fat). In the second set of experiments we administered 7-OH-DPAT (10, 50 and 100 microg/kg) to rats that had access to chow or HF diet for only 3 h per day (meal fed). In the third set of experiments we administered 7-OH-DPAT (10 and 50 microg/kg) to rats that had access to chow or HF diet after a 21-h food restriction. The 10 and 50 microg/kg doses significantly, but equally reduced intake of chow and HF diet in animals that were ad libitum fed. In animals that were meal-fed the dose response was effectively shifted to the right and the 10 microg/kg dose was ineffective at reducing intake. The 50 and 100 microg/kg doses significantly but equally reduced intake of both diets. In animals that were 21-h restricted and had access to chow both the 10 and 50 microg/kg doses were ineffective at reducing intake. However, in animals that had access to HF diet, 7-OH-DPAT dose-dependently reduced intake. These results support a potential role for the D3-R in ingestive behavior particularly in situations that involve a significant learned component.     

Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation,obesity and insulin resistance through nucleosome positioning

Background and Purpose

Sodium butyrate (NaB), an epigenetic modifier, is effective in promoting insulin sensitivity. The specific genomic loci and mechanisms underlying epigenetically induced obesity and insulin resistance and the targets of NaB are not fully understood.

Experimental Approach

The anti-diabetic and anti-obesity effects of NaB treatment were measured by comparing phenotypes and physiologies of C57BL/6J mice fed a low-fat diet (LF), high-fat diet (HF) or high-fat diet plus NaB (HF + NaB) for 10 weeks. We determined a possible mechanism of NaB action through induction of beneficial skeletal muscle mitochondrial adaptations and applied microccocal nuclease digestion with sequencing (MNase-seq) to assess whole genome differences in nucleosome occupancy or positioning and to identify associated epigenetic targets of NaB.

Key Results

NaB prevented HF diet-induced increases in body weight and adiposity without altering food intake or energy expenditure, improved insulin sensitivity as measured by glucose and insulin tolerance tests, and decreased respiratory exchange ratio. In skeletal muscle, NaB increased the percentage of type 1 fibres, improved acylcarnitine profiles as measured by metabolomics and produced a chromatin structure, determined by MNase-seq, similar to that seen in LF. Targeted analysis of representative nuclear-encoded mitochondrial genes showed specific repositioning of the −1 nucleosome in association with altered gene expression.

Conclusions and Implications

NaB treatment may be an effective pharmacological approach for type 2 diabetes and obesity by inducing −1 nucleosome repositioning within nuclear-encoded mitochondrial genes, causing skeletal muscle mitochondrial adaptations that result in more complete β-oxidation and a lean, insulin sensitive phenotype.     

Nongenetic model of type 2 diabetes: a comparative study

Seven-week-old male Sprague-Dawley (SD) rats were divided into six groups (LFC, LFD, HFC, HFD30, HFD40, HFD50) to determine whether animals receiving a low-fat (LF) diet plus nicotinamide-streptozotocin (NA-STZ) injection or animals receiving a high-fat (HF) diet plus STZ injection provide a better model of type 2 diabetes. After 2 weeks of feeding, diabetes was induced by intraperitoneal injection of NA (230 mg/kg BW) and STZ (65 mg/kg BW) in LFD, and STZ 30, 40, 50 mg/kg BW to HFD30, HFD40, HFD50 groups, respectively. Fasting blood glucose at 48-72 h and nonfasting blood glucose at 1 week after STZ injection were >200 and >600 mg/dl, respectively, in HFD40 and HFD50 groups while no significant difference was observed among other groups. Serum insulin concentration was significantly (p < 0.05) decreased in LFD, HFC, HFD30, and HFD40 groups compared to LFC and HFD50 groups. One animal died and other animals of the HFD50 group were in a critical condition. Serum lipid and liver glycogen were increased in HFD groups compared to other groups. The results of this study suggest that the HF diet-fed, 40-mg/kg BW STZ-injected SD rat is better than the LF diet-fed NA-STZ-injected rat as an animal model of human type 2 diabetes.     

饱和脂肪酸对AMPKa表达和活性的影响

目的探讨饱和脂肪酸对大鼠骨骼肌蛋白激酶(AMPKa)亚基表达及活性的影响,确定其在脂毒性发生中的地位和作用,为有效预防和控制脂毒性提供科学依据。方法雄性Wistar大鼠随机分为3组,每组10只,即对照组、高脂组和高脂加AMPKa激活剂组[二甲双胍50 mg/(kg.d),n=10]。喂养20周后,测定大鼠空腹和服糖后2 h血糖;用体外骨骼肌糖摄取试验评价大鼠骨骼肌胰岛素敏感性,Western blot法测定大鼠骨骼肌中AMPKa亚基和磷酸化AMPKa亚基蛋白水平。结果(1)与对照组比较,高脂组大鼠空腹血糖增加21.5%(P<0.05),服糖后2 h血糖增加28.3%(P<0.05),骨骼肌基础和胰岛素刺激后的糖摄取分别下降37.2%(P<0.05)和57.89%(P<0.01);(2)高脂组大鼠骨骼肌P-AMPKa和总AMPKa亚基蛋白水平分别下降46.1%(P<0.05)和79.4%(P<0.05);(3)与高脂组比较:二甲双胍显著上调AMPKa亚基的表达(P<0.05)和活性增加(P<0.05)。结论饱和脂肪酸通过降调AMPKa亚基表达和活性诱导大鼠胰岛素抵抗。     

Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat

The anti-obesity effects of crude saponin (CS) of Korean red ginseng (KRG) were investigated in the rat fed a high-fat (HF) diet. Male Sprague-Dawley (SD) rats became obese by feeding the HF diet over 5 weeks, while the control rats were fed a normal diet, and then both groups were treated with CS (200 mg/kg, i.p.) for 3 weeks. The body weight, food consumption, adipose tissues, and expression of appetite peptides such as leptin and neuropeptide Y (NPY) were investigated in rats fed normal and HF diet after treatment of CS. Administration of CS reduced body weight, food intake, and fat content in HF diet rats in a manner similar to those of the normal diet fed rats. The hypothalamic NPY expression and serum leptin level were reduced in HF diet rats after CS treatment. Our results suggest that CS may be useful in the treatment of obesity and related disorders as anti-obesity agents.     

NO-1886 inhibits size of adipocytes, suppresses plasma levels of tumor necrosis factor-alpha and free fatty acids, improves glucose metabolism in high-fat/high-sucrose-fed miniature pigs.

The synthetic compound NO-1886 is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides and elevating high-density lipoprotein cholesterol. Recently, we found that NO-1886 also had a plasma glucose-reducing action in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on the morphology of adipocytes, plasma levels of tumor necrosis factor-alpha (TNF-alpha) and free fatty acids (FFA) in miniature pigs fed a high-fat/high-sucrose diet. Our results showed that feeding a high-fat/high-sucrose diet to miniature pigs increased the size of adipocytes, and the plasma levels of TNF-alpha, FFA, and glucose. This diet also induced insulin resistance and impaired the acute insulin response to glucose loading. Supplementing 1% NO-1886 to the high-fat/high-sucrose diet inhibited adipocyte enlargement, and suppressed plasma levels of TNF-alpha, FFA, and glucose. The decrease in plasma TNF-alpha and FFA was simultaneous with the decrease in plasma glucose. We also found an increased whole body glucose clearance and an increased acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 improves the glucose metabolism in high-fat/high-sucrose diet-induced diabetic minipigs by decreasing fat deposit, and suppressing plasma TNF-alpha and FFA levels. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistant syndrome.     

Systemic and local effects of the Fusarium toxin deoxynivalenol (DON) are not alleviated by dietary supplementation of humic substances (HS)

The aim of this study was to examine the effects of a control diet (CON) or a Fusarium toxin contaminated diet (FUS) with and without HS (CON-HS and FUS-HS, respectively) on pigs during a 10-week growth trial starting at 35.1±3.2 kg live weight (n=12/group). Moreover, 2 additional choice feeding groups were included to test the ability of the pigs to differentiate between the CON and FUS diet. Feeding the FUS diets (～3 mg DON/kg) did not depress feed intake irrespective of HS addition. However, the pigs of the choice feeding groups recognised the FUS diets and acquired an ability to avoid these diets. DON residues were detected exclusively in the blood of pigs exposed to the FUS diets (7-21 ng/mL) but their levels were not affected by HS, suggesting their inefficiency in preventing DON absorption. While zonula occludens-1 protein expression and villus height in jejunum and ileum were not compromised by FUS feeding, the jejunal crypts were significantly deepened at 31% compared to the CON group. These changes had no consequences for nutrient digestibility or LPS levels in systemic blood (0.02-0.08 EU/mL). As portal LPS levels were not measured, FUS effects on intestinal LPS translocation cannot be excluded.     

Effect of Subchronic Metformin Treatment on Macronutrient Selection in Genetically Obese Zucker Rats

Abstract: Metformin has been particularly recommended to be used in obese type 2 diabetic patients because of its weight decreasing and serum lipid profile normalizing effects. In the present study the effects of subchronic metformin treatment on macronutrient selection, weight gain and plasma insulin and glucose were investigated in 20 genetically obese male Zucker rats which were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Half of the rats were given metformin hydrochloride 320 mg/kg/day up to 18 days in drinking water. The other half of the animals received normal drinking water as a control. Metformin treatment significantly reduced 24 hr carbohydrate (P<0.01), fat (P<0.001) and protein (P<0.01) intake. The proportion of fat of the total consumed energy was significantly increased by metformin (P<0.01) while the proportion of protein was decreased (P<0.05). In hunger stimulated feeding experiment metformin decreased selectively protein intake (P<0.01). Changes in macronutrient selection were associated with reduced body weight gain in metformin treated rats (P<0.001). Metformin markedly reduced the hyperinsulinaemia (P<0.01) and plasma glucose levels (P<0.05), which suggests improved glucose tolerance after metformin treatment. It is concluded that subchronic metformin treatment can modify the composition of energy intake in a macronutrient selective manner.     

Influence of diet palatability on the noradrenergic feeding response in the rat

Adult male rats which displayed a reliable feeding response to intrahypothalamic injections of norepinephrine (NE) on a chow diet were subsequently tested on one of three diets: an unpalatable quinine-adulterated meal, a palatable fat-adulterated meal, or a “neutral” unadulterated meal. The quinine diet completely blocked the NE feeding response, while the fat diet produced a small and unreliable reduction in the feeding response. When food deprived all groups increased their food intake, although the fat diet group tended to overeat, and the quinine diet group tended to undereat relative to the unadulterated diet group. The failure of the palatable fat diet to potentiate the NE feeding response does not support the hypothesis that this response mimics the ventromedial hypothalamic hyperphagia syndrome. The blocking effect of the quinine diet on NE feeding is consistent with other evidence which suggests that NE mediates the eating behavior induced by glucoprivation.