Influence of diet composition on food intake and hypothalamic neuropeptide Y (NPY) in the rat

Ingestion of a high carbohydrate (HC) or high fat (HF) diet induces obesity in association or not with modifications of the feeding behaviour. Effects of diet composition on NPY, a powerful stimulant of weight gain and food intake (particularly carbohydrates), are not known. That is why we measured NPY in 10 microdissected brain nuclei of rats fed either a HC diet (69% of energy from carbohydrates), a HF diet (68% of energy from fat) or a control well-balanced diet (54% of energy from carbohydrates; 30% of energy from fat) during a 14-day period. Total caloric intake was significantly greater (+12%) in rats fed on the HF diet than in the control and HC rats. HF rats also gained more weight than the two other groups (47.5 +/- 2.4 g vs 37.6 +/- 2.6 g (control) and 29.1 +/- 1.4 g (HC); p less than 0.001). NPY variations were restricted to two hypothalamic areas. In the parvocellular part of the paraventricular nucleus, NPY was smaller with the HC diet than with the HF diet (42.1 +/- 2.3 vs 49.5 +/- 2.7 ng/mg protein; p less than 0.05). A decrease was observed in the lateral hypothalamus with the HF diet when compared with the control diet (11.3 +/- 0.7 vs 14.6 +/- 1.1 ng/mg protein; p less than 0.05). No variations were observed either in other hypothalamic nuclei such as arcuate, dorsomedian, ventromedian or suprachiasmatic nuclei or in extra-hypothalamic areas such as the ventral tegmental area or submamillary bodies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sensory responses, dietary-induced obesity and biochemical values in Sprague-Dawley rats

Food intake and body weight gain variability in Sprague-Dawley (SD) rats exposed to a palatable high-fat diet were examined in relation to sensory responses and biochemical parameters in two experiments. In the first experiment, varying sucrose concentrations (4-32% wt./vol.) were randomly presented for 20 minutes to ad lib chow-fed rats. Each rat's sensory response was expressed as Beta (B), or the slope of the regression between solute intake and concentration, and used to assign rats to diet groups. In the second experiment, responsiveness to fat emulsions (1-37%) were similarly measured and categorized. In both experiments sensory responses to sucrose were significantly related to weight gain/fatness on the high-fat diet (lab chow-corn oil). Sensory responsiveness to the fat emulsions was unrelated to sucrose responsiveness or to high-fat feeding. Biochemical parameters (insulin, cholesterol, triglycerides, lipoproteins) reflected increased caloric (fat) intake, as well as sucrose responsiveness. Predictors (sensory responses, biochemical values) of response to chronic (4 months) or short-term (less than 2 months) high-fat diets are discussed.     

The effects of a high-fat, high-fructose, and combination diet on learning, weight, and glucose regulation in C57BL/6 mice

The objective of the study was to determine the effects of a high-fructose diet, a high-fat diet and a combination high-fructose/high-fat diet on weight gain, blood glucose regulation, and cognitive function in C57BL/6 mice. Thirty-eight male mice aged 7 weeks were placed on one of four different diets for 3 months: standard chow and water (n=8), standard diet and access to a fructose solution as the only intake of water (n=8), high-fat diet and water (n=11), and high-fat diet and fructose solution (n=11). Weights were measured 10 times over a 3-month period. Blood glucose regulation was measured using a glucose tolerance test. Cognitive testing consisted of learning an operant bar-pressing task and was performed in the absence of fructose intake. At the end of the experiment, the density of the fructose-specific glucose transporter GLUT5 was measured in the hippocampus, frontal cortex, sensori-motor cortex and cerebellum. The high-fat and the combined high-fat/high-fructose groups gained significantly more weight than the control group. The high-fat group and combined group had significantly higher levels of blood glucose than the control group. The high-fructose group learned the operant task faster than the control group, but the high-fat/high-fructose group was not different from control indicating that the facilitative effect of prior fructose intake was abolished when a high-fat diet was added. Addition of fructose to the diet did not result in an increase of brain GLUT5 density suggesting that the learning improvement were not dependent on plastic upregulation of GLUT5 fructose transporter. The results show that, contrary to high-fat diets, access to fructose in mice did not lead to increased weight and impaired glucose tolerance. The present experiment confirm the deleterious impact of high-fat diets on glucose regulation and weight but suggest that high-fructose diets, contrary to what has been observed in hamsters, do not have the same effect.     

Differential Effects of Restricted Versus Unlimited High-Fat Feeding in Rats on Fat Mass, Plasma Hormones and Brain Appetite Regulators

The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague–Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.     

Calorie restriction of a high-carbohydrate diet elevates the threshold of PTZ-induced seizures to values equal to those seen with a ketogenic diet

The purpose of this study was to evaluate the contributions of ketonemia, caloric restriction, and carbohydrates to seizure protection in rats fed selected diets. Male Sprague-Dawley rats were fed experimental diets of two basic types, one high in carbohydrates and restricted to 90, 65, or 50% of the normal daily caloric requirement and the other a normal rodent chow diet restricted to 90 or 65% of the daily caloric requirement. After consuming their respective diets for 20 days, animals were subjected to tail-vein infusion of pentylenetetrazole (PTZ) to determine seizure threshold, taken as the dose required to evoke the first clonic reaction. Seizure thresholds were compared to those of rats fed control diets of either normal rodent chow fed ad libitum or a standard high-fat (ketogenic) diet calorie-restricted to 90% of daily caloric requirement, all animals age- and weight-matched at the time of diet onset. All diets were balanced for vitamins and minerals and contained at least 10% protein (by weight). Seizure threshold and ketonemia were elevated in both experimental diets in approximate proportion to the degree of calorie restriction. Animals fed the most severely restricted high-carbohydrate diet (50%) had seizure thresholds equal to those fed the ketogenic diet but had significantly lower ketonemia.     

Acute Homeostatic Responses to Increased Fat Consumption in MCH1R Knockout Mice

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide which has been shown to regulate energy homeostasis. Using genetic knockout mice lacking the MCH1 receptor (MCH1R), we investigated how these mice adapt to metabolic changes caused by excessive caloric consumption. We show that the MCH system is one of the players mediating behavioral and metabolic responses upon increased caloric consumption. MCH1R knockout mice showed decreased tendency of food intake upon exposure to a high-fat diet. They also are resistant to gain weight upon high-fat diet by increasing fat metabolism. Therefore, the MCH system is important in regulating metabolic responses upon various environmental stimuli such as high-fat diet.     

Social stress interacts with diet history to promote emotional feeding in females

Stress-induced eating disorders cause significant health problems and are often co-morbid with mood disorders. Emotional feeding, particularly in women, may be important for the development of obesity and failed attempts to lose weight. However, prospective studies assessing the effect of chronic psychosocial stress on appetite in different dietary environments in females are lacking. The present study tested the hypothesis that chronic psychosocial stress would increase consumption of high caloric diet and this emotional feeding would persist even when a healthier diet was available. Socially housed female rhesus monkeys were studied to address whether subordination increases caloric intake when a high fat and sugar diet (HFSD) was available concurrently with a low fat, high fiber diet (LCD). Cortisol responsivity and food intake were quantified during this choice phase and when only the LCD was available. The order of diet condition was counterbalanced to assess whether a history of HFSD would affect appetite. All females preferred the HFSD but subordinates consumed significantly more calories during the choice phase. The increased calorie intake was maintained in subordinate monkeys even after withdrawal of the HFSD. Subordinate females demonstrated reduced glucocorticoid negative feedback, with post dexamethasone serum cortisol levels significantly predicting intake of the HFSD but not the LCD during the choice condition. The cortisol response to an acute stressor significantly predicted subsequent intake of a HFSD in all females. Continual exposure to the psychosocial stress of subordination in female monkeys results in excess caloric intake of foods that mimic a western dietary environment. In addition, this social stressor interacts with a history of HFSD intake to promote increased feeding even in a healthy dietary environment.     

Large changes in food intake in diabetic rats fed high-fat and low-fat diets

Groups of male Sprague-Dawley rats were predominantly fed either a high-fat or a high-carbohydrate (CHO) diet. For designated 2-day periods, their diets were switched. After baseline measurements of food and water intake, the rats were made diabetic by injections of either 40 or 46-50 mg/kg streptozotocin. Food and water intake gradually increased over a 15-day period for rats on the CHO diet. Whenever the diets were switched, many of the rats showed large changes in food and fluid intake. Body weight showed a gradual decline, but the rats retained half of the dissectable abdominal body fat at sacrifice. Measurements of plasma glucose, insulin and glucagon proved that the rats were diabetic. The changes in average food intake were reasonably consistent with the "utilizable fuel" theory for the control of food intake assuming that the CHO component of each diet was non-utilizable. The distribution of the fat/CHO utilizable fuel ratio in both experiments was flat and non-normal showing that some rats ate as much of the high fat diet as the high CHO diet. Other rats tended to avoid the high fat to an extent that was greater than predicted by the theory, suggesting that the fat diet may have caused malaise. Thus, the individual rat data did not provide strong support for the "utilizable fuel" theory.     

Exaggerated feeding response to central galanin-like peptide administration in diet-induced obese rats

Galanin-like peptide (GALP) is a newly identified neuropeptide implicated in the regulation of metabolism and reproduction. GALP gene expression is decreased in the hypothalamus of genetically obese rodents, such as fa/fa rats and ob/ob mice, and central administration of GALP increases feeding in satiated rats. The effect of dietary obesity on GALP-induced feeding is unknown, so this study characterized the effects of central administration of GALP on feeding in a rat model of diet-induced obesity. Male Sprague-Dawley rats (n = 21) were randomly assigned to receive standard laboratory chow (12% fat as kcal) or high-fat cafeteria diet (35% fat) for 12 weeks before intracerebroventricular (icv) cannulae were implanted. Seven days later, rats received 0,0.2 or 0.3 nmol doses of GALP in randomized order at least 48 h apart. Food intake was measured at 0.5,1,2, 4 and 24 h post administration and body weight was measured at 24 h. Rats were maintained on their respective diets throughout the entire feeding experiment. Implementation of the high-fat diet led to significantly greater caloric intake (230%) and body weight (28%) compared to chow-fed control rats. GALP-induced feeding was rapid and maximal in both dietary groups at 30 min post injection. The 0.3 nmol dose of GALP led to significantly larger increases in caloric intake in high-fat fed rats than in chow-fed controls (35.4 +/- 3.7 and 22.1 +/- 1.3 kcal, respectively, at 30 min). It is not known if diet-induced obesity alters endogenous GALP levels, but our data suggest that adaptive responses in GALP signaling might occur during chronic overfeeding. One possible explanation is an increased sensitivity and/or number of specific GALP receptors, although actions of exogenous GALP may also represent pharmacological actions at galanin receptors.