Suppression of QRFP 43 in the hypothalamic ventromedial nucleus of Long-Evans rats fed a high-fat diet

QRFP 43 is a RFamide peptide present in the ventromedial nucleus (VMN) and lateral hypothalamus. It stimulates food intake in mice and its chronic infusion induces hyperphagia, reduced thermogenesis, and obesity. In this experiment, we measured it in the VMN and lateral hypothalamus of Long-Evans rats fed either a high-fat (HF), control, or low-fat (LF) diet in parallel with plasma leptin, adiposity, and energy intake. After 8 weeks of ad libitum diet intake, energy intake of HF rats was similar to that of control rats. In the VMN, QRFP 43 was completely undetectable in HF rats and its tissue concentration in control rats was significantly lower than in LF rats (p < 0.03). HF rats had higher levels of leptin than control rats (+24%; p < 0.03) and than LF rats (+42%; p < 0.002). The QRFP 43 concentration in the VMN was inversely correlated with plasma leptin (r = −0.34; P < 0.04) and with the adipogenic index of the diet (p < 0.02) but not with insulin. We conclude that the decrease of the orexigenic drive mediated by QRFP 43 could contribute to the normalization of caloric intake in HF diet fed rats. QRFP 43 might play a role downstream of leptin in the regulation of feeding behavior.     

Reduced CCK signaling in obese-prone rats fed a high fat diet

Deficits in satiation signaling during obesogenic feeding have been proposed to play a role in hyperphagia and weight gain in animals prone to become obese. However, whether this impaired signaling is due to high fat (HF) feeding or to their obese phenotype is still unknown. Therefore, in the current study, we examined the effects of CCK-8 (0.5, 1.0, 2.0, and 4.0 μg/kg) on suppression of food intake of HF-fed obese prone (OP) and resistant (OR) rats. Additionally, we determined the role of endogenous CCK in lipid-induced satiation by measuring plasma CCK levels following a lipid gavage, and tested the effect of pretreatment with devazepide, a CCK-1R antagonist on intragastric lipid-induced satiation. Finally, we examined CCK-1R mRNA levels in the nodose ganglia. We show that OP rats have reduced feeding responses to the low doses of exogenous CCK-8 compared to OR rats. Furthermore, OP rats exhibit deficits in endogenous CCK signaling, as pretreatment with devazepide failed to abolish the reduction in food intake following lipid gavage. These effects were associated with reduced plasma CCK after intragastric lipid in OP but not OR rats. Furthermore, HF feeding resulted in downregulation of CCK-1Rs in the nodose ganglia of OP rats. Collectively, these results demonstrate that HF feeding leads to impairments in lipid-induced CCK satiation signaling in obese-prone rats, potentially contributing to hyperphagia and weight gain.     

Electrical activity of the amygdala and the septum of rats on a high fat or a high protein diet

The authors studied biopotentials in the region of the amygdala and the septum of rats fed on a standard, high protein or high fat diet. During the first 3-6 days after changing from the standard to the high protein or high fat diet, a decrease in the amplitude of electrical activity was found in both the regions in question. After 3 days on the high fat or the high protein diet, an increase was found in the frequency of electrical activity in the amygdala or the septum, according to the type of diet. A study of the amplitude of electrical activity showed that the electrical potential in the septum was always lower than in the amygdala. The frequency spectrum analysis showed a marked change in the superimposed frequency curve only in animals fed on the high fat diet.     

Antiatherogenic effect of taurine in high fat diet fed rats

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.     

Influences of cerebellar interpositus nucleus and fastigial nucleus on neuronal activity of lateral hypothalamic area

Stimulation of cerebellar interpositus nucleus and (astigial nucleus could influence the neuronal activi-ty of lateral hypothalamic area in the cat, and some of the neurons which respond to the cerebellar stimulations are glucose-sensitive neurons. These results suggest that the cerebellum is involved not only in motor control, but also in the regulation of non-somatic functions through the cerebello-hypothalamic pathways.     

The necessity of niacin in rats fed on a high protein diet

It is known that niacin itself is not necessary in rats when tryptophan is given in adequate amounts, because rats can biosynthesize niacin from tryptophan. In our experiment, young rats were fed on a 20%, 40%, 60%, or 70% casein diet with or without niacin. The rats fed on the 20%, 40%, and 60% casein diets did not require niacin for growth, but the rats fed on the 70% casein diet needed it. This phenomenon was attributed to the supposition that liver aminocarboxymuconate-semialdehyde decarboxylase activities increased according with the dietary casein levels. The conversion ratio of tryptophan-niacin in rats fed on the 70% casein diet became extremely low, and then the rats needed niacin.     

Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat.

Rats were fed ad libitum on either a standard, high-carbohydrate, chow diet or a similar diet supplemented with 15% unsaturated fat (corn oil). Hepatocytes were prepared either during the dark phase (D6-hepatocytes) or during the light phase (L2-hepatocytes) of the diurnal cycle. In hepatocytes from rats fed on the unsaturated-fat-containing diet, secretion of very-low-density lipoprotein (VLDL) triacylglycerol was inhibited to a greater extent in the D6- than in the L2-hepatocytes. Plasma non-esterified fatty acid concentrations were elevated to the same extent at both D6 and L2 in the unsaturated-fat-fed animals. The secretion of VLDL esterified and non-esterified cholesterol was relatively insensitive to changes in the unsaturated-fat content of the diet. This resulted in proportionate increases in the content of these lipid constituents compared with that of triacylglycerol in the nascent VLDL. There was also an increase in the ratio of esterified to non-esterified cholesterol in the nascent VLDL produced by hepatocytes of the unsaturated-fat-fed animals. In the D6-hepatocytes from the unsaturated-fat-fed animals, the decrease in the secretion of VLDL triacylglycerol could not be reversed by addition of exogenous oleate (0.7 mM) to the incubation medium. In contrast, addition of a mixture of lactate (10 mM) and pyruvate (1 mM) stimulated both fatty acid synthesis de novo and the rate of VLDL triacylglycerol secretion. Secretion of esterified and non-esterified cholesterol also increased under these conditions. Insulin suppressed the secretion of VLDL triacylglycerol and cholesteryl ester under a wide range of conditions in all types of hepatocyte preparations. Non-esterified cholesterol secretion was unaffected. In hepatocytes prepared from the fat-fed animals, these effects of insulin were more pronounced at D6 than at L2. Glucagon also inhibited VLDL lipid secretion in all types of hepatocyte preparations. The decrease in cholesterol secretion was due equally to decreases in the rates of secretion of both esterified and non-esterified cholesterol.     

Steady state changes in mitochondrial electrical potential and proton gradient in perfused liver from rats fed a high fat diet

In this work the protonmotive force (p), as well as the subcellular distribution of malate, ATP, and ADP were determined in perfused liver from rats fed a low fat or high fat diet, using density gradient fractionation in non acqueous solvents.Rats fed a high fat diet, despite an enhanced hepatic oxygen consumption, exhibit similar p to that found in rats fed a low fat diet, but when we consider the two components of p, we find a significant decrease in mitochondrial/cytosolic pH difference (pH_m) and a significant increase in mitochondrial membrane potential (_m) in rats fed a high fat diet compared to rats fed a low fat diet, which tend to compensate each other. In rats fed a high fat diet the concentration ratio of malate and ATP/ADP does not reflect the changes in pH_m and _m, which represent the respective driving force for their transport.The findings are in line with an increase in substrate supply to the respiratory chain which is, however, accompanied by a higher energy turnover in livers from HFD rats. By this way the liver could contribute to the lack of weight gain from the high caloric intake in HFD rats.     

Effect of chemically different calcium antagonists on lipid profile in rats fed on a high fat diet.

Different classes of calcium antagonists, viz. verapamil (diphenylalkylamine), diltiazem (benzothiazepine), nifedipine, felodipine and nimodipine (dihydropyridines), were examined for their effects on lipid profile in rats. Clofibrate was the reference standard. Clofibrate significantly prevented the rise of serum triglycerides and total cholesterol produced by high fat diet and raised antiatherogenic index to 1.6 times than that of high fat diet controls. Of the calcium antagonists studied, felodipine was most effective in preventing the rise of serum triglycerides and total cholesterol in high fat diet fed rats. Felodipine's antiatherogenic index was very high (886%)--much more than that of clofibrate (303%). Diltiazem and nimodipine which also significantly prevented the rise in triglycerides and total cholesterol produced by high fat diet had a moderately beneficial antiatherogenic index similar to that of clofibrate. Though verapamil and nifedipine slightly increased the triglyceride levels, total cholesterol levels were reduced only by verapamil and not by nifedipine. Despite this both these drugs moderately raised antiatherogenic index similar to clofibrate.     

电刺激下丘脑外侧区对大鼠胃缺血-再灌注损伤的影响

采用夹闭大鼠腹腔动脉30min,松开动脉夹血流复灌60min的胃缺血－再灌注损伤(gastric ischemia reperfusion injury,GI-RI)模型,用电和化学刺激,电损毁的方法观察了下丘脑外侧区（lateral hypothalamic area,LHA)对GI－RI的影响,并对其机制进行了初步分析,结果表明：（1）以0．2,0．4,0．6mA的电流强度刺激LHA,GI－RI均显著加重,且有强度－效应依赖关系,LHA内注射L－谷氨酸（L－Glu)后,对LI－RI的效应与电刺激相似,电损毁双侧LHA,GI－RI面积较电刺激组明显减小;（2）损毁双侧背侧迷走复合体（dorsal vagal complex,DVC)或切损毁是LHA,GI－RI面积较电刺激组明显减小;（2）损 侧背侧迷走复合体（dorsal vagal complex,DVC)或切断膈下迷走神经均能取消电刺激LHA加重GI－RI的作用。（3）电刺激LHA使缺血－再灌注（ischemia-reperfusion,I-R)的胃粘膜丙二醛（MDA）含量升高,超氧化物歧化酶（SOD）活性降低;（4）电刺激LHA使I－R的胃液量和总酸排出量增多,而酸度,胃蛋白酶活性和胃壁结合粘液量等无明显改变,结果提示;LHA是对GI－RI具有加重作用的中枢部位,其作用是通过DVC及迷走神经下传的,电刺激LHA加重GI－RI的作用与胃粘膜MDA含量增加,SOD活性降低,胃液量和总酸排出量增加等因素有关,而似与酸度,胃蛋白酶活性,胃壁结合粘液量等因素无关。     

Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine aminotransferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VMH) in CCl4-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VMH stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl4 injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve (hepatic nerves), possibly by affecting liver metabolism more than the blood flow change to the liver.     

The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet.

This study was designed to examine the time-course of response to inhibition of fatty acid (FA) oxidation in rats rendered mildly diabetic with streptozotocin and fed a high fat diet (50% of energy derived from fat). Etomoxir, a specific carnitine palmitoyltransferase (CPT-1) inhibitor, was administered subcutaneously (12.5 mg/kg) to inhibit long chain fatty acid oxidation. Diabetic and non-diabetic control rats were maintained on the high fat diet. Following an overnight fast, glucose, free fatty acid (FFA) and triglyceride (TG) concentrations were determined after three days, one week and four weeks of treatment. The effect of Etomoxir treatment in reducing fasting glucose concentrations was not evident until after one week, while fasting FFA and TG concentrations were already reduced after three days treatment. All of these changes were maintained over the four week period (P less than 0.001), resulting in reduced levels of fasting plasma glucose (17.6 +/- 2.4 vs 22.3 +/- 1.9 mmol/l), fasting plasma TG (0.32 +/- 0.07 vs 0.98 +/- 0.14 mmol/l) and fasting serum FFA (1.52 +/- 0.26 vs 3.51 +/- 0.69 mEq/l). In addition, the improvements in glucose and lipid levels were accompanied by restored rates of growth towards that of non-diabetic control rats. These results suggest that the short term inhibition of FA oxidation improves fasting glucose, FFA and TG concentrations in diabetic rats fed a high fat diet.     

Effect of capsaicin on skeletal muscle lipoprotein lipase in rats fed high fat diet

A synthetic analogue of capsaicin (0.2 mg%) fed to female Wistar rats along with a high fat diet for 11 weeks, lowered adipose tissue weight and also liver and serum triglycerides. The compound elevated total post heparin plasma lipase and skeletal muscle lipase activities. The increase in the latter indicates the possible mechanism by which capsaicin enhances serum triglyceride uptake by muscle tissue and in turn lowers triglyceride levels. A single dose of capsaicin even at a much higher level failed to lower serum triglycerides emphasizing the necessity of continuous ingestion of capsaicin for exerting its hypolipidemic effect.     

Effect of short-term exercise training on muscle glycogen in resting conditions in rats fed a high fat diet.

It has been reported that exercise training increases muscle glycogen storage in rats fed a high carbohydrate (CHO) diet in resting conditions. The purpose of this study was to examine whether a 3-week swimming training programme would increase muscle glycogen stores in rats fed a high-fat (FAT) diet in resting conditions. Rats were fed either the FAT or CHO diet for 7 days ad libitum, and then were fed regularly twice a day (between 0800 and 0830 hours and 1800 and 1830 hours) for 32 days. During this period of regular feeding, half of the rats in both dietary groups had swimming training for 3 weeks and the other half were sedentary. The rats were not exercised for 48 h before sacrifice. All rats were killed 2 h after their final meal (2030 hours). The glycogen contents in red gastrocnemius muscle, heart and liver were significantly higher in sedentary rats fed the CHO diet than in those fed the FAT diet. Exercise training clearly increased glycogen content in soleus, red gastrocnemius and heart muscle in rats fed the CHO diet. In rats fed the FAT diet, however, training did not increase glycogen content in these muscles or the heart. Exercise training resulted in an 87% increase of total glycogen synthase activity in the gastrocnemius muscle of rats fed the CHO diet. However, this was not observed in rats fed the FAT diet. The total glycogen phosphorylase activity in the gastrocnemius muscle of the rats of both dietary groups was increased approximately twofold by training.(ABSTRACT TRUNCATED AT 250 WORDS)