Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.
 ...
PMID:Hypothalamic neuropeptide expression after food restriction in Zucker rats: evidence of persistent neuropeptide Y gene activation. 136 27

Increased hypothalamic neuropeptide Y levels have previously been demonstrated in several hypothalamic nuclei of the (fa/fa) Zucker rat. This study set out to characterise hypothalamic NPY receptors in both genotypres and to study the effect of exogenous NPY on feeding behavior in these rats. Spontaneous daytime food intake was raised in the obese rat (p less than 0.05). Total hypothalamic receptor density (Bmax) was reduced in the obese rat compared with the lean rat (by 56%, p less than 0.005), but affinity remained unaltered. The lowest dose of NPY tested (23.5 pmol) stimulated daytime feeding in lean rats after 1, 2 and 3 hours but was inaffective in the obese rat (p less than 0.05). At two higher doses (235 pmol and 2.35 nmol), NPY was equipotent in both genotypes over 1 and 2 hours but NPY-induced feeding was attenuated over 3 hours in the obese rat. These results suggest an overactive endogenous NPYergic system in the obese (fa/fa) rat which might contribute to hyperphagia and obesity in this strain.
 ...
PMID:Hypothalamic neuropeptide Y receptor characteristics and NPY-induced feeding responses in lean and obese Zucker rats. 165 13

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.
 ...
PMID:Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. 194 36

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)
 ...
PMID:Influence of diet composition on food intake and hypothalamic neuropeptide Y (NPY) in the rat. 209 53

Numerous hypothalamic peptides are involved in the control of eating behaviour. We assessed plasma and cerebrospinal fluid (CSF) levels of SRIH, beta-endorphin (beta-EP), CRH, NPY and GHRH in a group of massively obese patients and in normal weight subjects. In the obese patients, CSF SRIH and beta-EP levels were significantly reduced and increased, respectively, compared with controls (20.6 +/- 2.62, mean +/- s.e.m., vs 34.5 +/- 2.14 pg/ml, P < 0.05, for SRIH and 111.2 +/- 5.00 vs 80.4 +/- 5.32 pg/ml, P < 0.001, for beta-EP). Considering the data of obese and control subjects altogether, SRIH and beta-EP concentrations correlated negatively and positively, respectively, with BMI values (r = -0.641, P < 0.005 and r = 0.518, P < 0.05). No significant differences were observed in CSF levels of CRH, NPY and GHRH between obese and normal weight subjects, though GHRH levels were close to the assay sensitivity. CSF concentrations of CRH were positively correlated with those of SRIH in obese patients (r = 0.60, P < 0.05) and with those of NPY both in obese (r = 0.69, P < 0.02) and in control subjects (r = 0.83, P < 0.005). Plasma levels of SRIH, beta-EP, NPY and GHRH did not differ significantly in the two groups of subjects; plasma CRH was undetectable. Our results argue against the hypothesis of an enhanced SRIH tone as the cause of impaired GH secretion in obese patients, a primary defect in GHRH or GH release seems more likely. Moreover, they emphasise the importance of an increased tone of endogenous opioids in the pathophysiology of human obesity.
 ...
PMID:Cerebrospinal fluid and plasma concentrations of SRIH, beta-endorphin, CRH, NPY and GHRH in obese and normal weight subjects. 771 86

Food Intake is reciprocally related to the activity of sympathetic nerves to brown adipose tissue. This reciprocal or feedback relation is shown for hypothalamic lesions, drugs, and many peptides. These peptides also modulate intake of specific nutrients. Galanin and opioids increase fat intake, whereas enterostatin decreases fat intake. NPY increases carbohydrate intake and growth hormone releasing hormone decreases protein intake. The activity of the sympathetic nervous system is low in obesity and adrenalectomy reverses this decrease in sympathetic activity and reverses or stops the progression of obesity. One mechanism for this effect of adrenal steroids is through a transacting substance which is involved in steroid actions and the production of obesity.
 ...
PMID:Food intake, sympathetic activity, and adrenal steroids. 822 Nov 49

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY; 10 micrograms/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver and adipose tissue lipogenic activity. It also increased basal morning corticosteronemia. When NPY-induced hyperphagia was prevented by pair-feeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under the ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose tissue; it resulted in an increase total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and metabolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperphagia was prevented by pair-feeding, it was, thus, shown that icv NPY per se induces peripheral hormonal and metabolic alterations via efferent routes, which remain to be determined. The effects of icv NPY reported in this study are similar to the defects observed in the early phase of genetic obesity in rodents, the hypothalamus of which has increased NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity.
 ...
PMID:Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. 840 18

NPY is synthesized in the hypothalamic arcuate nucleus (ARC), and NPY injected into the paraventricular nucleus (PVN), the main site of NPY release, induces hyperphagia and reduces energy expenditure. Hypothalamic NPY mRNA and NPY levels are increased in fatty Zucker rats, consistent with increased NPY release. This could explain the hyperphagia and reduced energy expenditure, which lead to obesity in the fatty Zucker rat. We have therefore compared NPY secretion in the PVN of conscious fatty and lean Zucker rats using push-pull sampling. The NPY secretory profile was consistently higher in fatty Zucker rats than in lean rats throughout the 3-h study period (P < 0.01), and mean NPY secretion over the whole 3 h was increased 2-fold in the fatty rats (P < 0.001). We conclude that fatty Zucker rats have increased NPY release in the PVN. This observation further supports the hypothesis that increased activity of the NPYergic ARC-PVN pathway may contribute to obesity in the fatty Zucker syndrome.
 ...
PMID:Increased neuropeptide Y secretion in the hypothalamic paraventricular nucleus of obese (fa/fa) Zucker rats. 853 35

Neurons containing serotonin (5-HT), a potent anorexic agent, come into contact with neuropeptide Y-ergic neurons, that project from the arcuate nucleus (ARC) to the paraventricular nucleus (PVN). NPY powerfully stimulates feeding and induces obesity when injected repeatedly into PVN. We hypothesize that 5-HT tonically inhibits the ARC-PVN neurons and that balance between the two systems determines feeding and energy homeostasis. This study aimed to determine whether central injection of the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA), which increases feeding, increased hypothalamic NPY and NPY mRNA levels. pCPA (10 mg/kg in 3 microliters) was administered into the third ventricle either as a single injection (n = 8) or daily for 7 days (n = 8). Control rats received a similar injection of saline. pCPA significantly increased food intake compared with controls after both single and repeated injections (P < 0.05). NPY levels were measured by radioimmunoassay in microdissected hypothalamic extracts. NPY levels in the acutely treated group were significantly increased in the paraventricular nucleus (PVN; by 41%, P = 0.01), anterior hypothalamic area (AHA; by 34%, P < 0.01) and lateral hypothalamic area (LHA; by 41%, P < 0.02). In the 7-day-treated group, NPY levels were also increased in the same areas, i.e. PVN (by 24%, P < 0.01), AHA (by 30%, P < 0.01) and LHA (by 38%, P = 0.01). There were no significant changes in the ARC or any other region or in hypothalamic NPY mRNA levels. pCPA administration increased NPY levels in several regions notably the PVN. This is a major site of NPY release, where NPY injection induces feeding. We suggest that the hyperphagia induced by pCPA is mediated by increased NPY levels and secretion in the PVN. This is further evidence for interactions between NPY and 5-HT in the control of energy homeostasis.
 ...
PMID:Increased feeding and neuropeptide Y (NPY) but not NPY mRNA levels in the hypothalamus of the rat following central administration of the serotonin synthesis inhibitor p-chlorophenylalanine. 882 73

A reduction in fat intake may be achieved by making educated choices to reduce total calorie intake, to consume a lower quantity of total fats, or to modify the ratio of saturated-to-polyunsaturated lipids. Leptin agonists or NPY or CCK antagonists may prove to be useful to diminish appetite and thereby reduce the total intake of food. But eating has such cultural, social, and hedonistic attributes that such a single-pronged approach is unlikely to be successful. The use of fat substitutes may prove to be popular to provide a wide range of snack food options, but these are likely to be of minimal use in weight reduction programs because of their distribution of additives in only a limited number of foods. The inhibitors of lipid digestion will be modestly successful in the short term; their long-term success will be influenced by gastrointestinal adverse effects and the need to consume fat-soluble vitamin supplements to prevent the development of fat-soluble vitamin deficiencies. The inhibition of lipid absorption is an attractive targeted approach for the treatment of obesity, since this would reduce the uptake of visible as well as invisible fats, which would potentially offer convenient dosing, and could also be a means to inhibit secondarily the uptake of carbohydrate calories.
 ...
PMID:Inhibition of lipid absorption as an approach to the treatment of obesity. 930 43


1 2 3 4 5 6 7 8 9 10 Next >>