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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid composition of the diet ingested by reference and cafeteria diet-fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet. Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids. In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age-or size-of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the 'blueprint for growth' which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accruing protein with high rates throughout. Diet composition--and not protein availability or quality--induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity. There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both 'models' of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization.
Mol Cell Biochem 1993 Apr 07
PMID:Individual amino acid balances in young lean and obese Zucker rats fed a cafeteria diet. 851 Jun 73

Obese Zucker rats maintain normal rates of linear growth and circulating concentrations of insulin-like growth factor-I (IGF-I) and of IGF-binding protein-3 (IGFBP-3) in spite of low GH secretion. The mechanisms underlying this GH-independent growth in obesity are unknown. To assess whether the liver expression of the GH receptor (GHR) messenger RNA (mRNA) is increased and/or if the liver expression of IGFBP-3 mRNA is maintained in the obese, Zucker rats of both genders and phenotypes (four groups, n = 6/group) were studied at 12 weeks of age. By Northern analysis, mRNA levels for GHR and GHBP were not increased in obese rats compared to their sex-matched lean littermates; the expression of these two transcripts was sexually dimorphic and the changes in GHBP mRNA/GHR mRNA ratios associated with obesity were sex-specific. In both genders, IGFBP-1 and IGFBP-3 mRNAs were decreased in the obese. We concluded that the GH-independent growth of obese Zucker rats is not due to increased GHR mRNA or to maintained IGFBP-3 mRNA levels in the liver.
Mol Cell Endocrinol 1995 Sep 22
PMID:The growth hormone (GH)-independent growth of the obese Zucker rat is not due to increased levels of GH receptor messenger RNA in the liver. 867 29

Certain differences in regional fat distribution might be explicable by subtle hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. We examined prospectively PA function relative to abdominal obesity defined by waist-to-hip circumference ratio (WHR) in 71 normotensive men aged 30-55 years. Basal PA activity was assessed by measurements of serum cortisol and plasma corticotropin (ACTH) concentrations during the oral glucose tolerance test (OGTT). Functional activity was examined by dexamethasone suppression and ACTH stimulation tests; responses of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol, dehydroepiandrosterone (DHEA), and androstenedione were determined. When the subjects were divided into tertiles for the WHR, the ratio of mean ACTH to mean cortisol during the OGTT was increased (p < 0.05), and the ratio of urinary cortisol to body-mass index was decreased (p < 0.01), whilst the net increments of cortisol (p < 0.05) and 17-OHP (p < 0.05) from 0 to 60 min, as well as the ratio of 17-OHP to S increments (p < 0.05) after ACTH were elevated in the highest vs lowest WHR tertile. The ratio of mean ACTH to mean cortisol (r = 0.495; p < 0.001) during the OGTT, the ratio of net 17-OHP to S increments (r = 0.404; p < 0.001), and the net DHEA (r = 0.276; p = 0.020) and 17-OHP (r = 0.336; p = 0.005) responses to ACTH at 60 min correlated with WHR. In multivariate analyses the ratio of mean ACTH to cortisol, cortisol response to ACTH, and the ratio of net 17-OHP to S increments were all significant predictors of WHR independent of smoking, physical activity, and BMI explaining 49.0% of the variance in WHR. Thus, abdominal obesity may be associated with decreased activity of adrenal 21-hydroxylase. Either obesity-related functional alteration of 21-hydroxylase activity or the high carrier prevalence of genetic defects of this enzyme may explain these findings.
J Steroid Biochem Mol Biol 1996 Apr
PMID:Pituitary-adrenocortical function in abdominal obesity of males: evidence for decreased 21-hydroxylase activity. 880 94

Differentiation of adipogenic precursor cells into mature adipocytes is a complex phenomenon, characterized by an ordered expression of adipocyte-specific genes, triggered by a set of interacting transcription factors. The most important transcription factors involved in this process are the gamma form of peroxisome proliferator activated receptors (PPAR gamma) and the various members of the CCAAT enhancer binding proteins (alpha, beta, and delta). In addition to PPAR gamma and these enhancer binding proteins, several other transcription factors, including ADD-1 (SRE-BP), HMGI-C, are involved in regulating this process. Altered activity and/or expression of these transcription factors, will induce the expression of target genes in the differentiating cells, ultimately resulting in the phenotypical characteristics of the adipocytes. It is speculated that modulation of these transcription factors by either pharmacological or dietary manipulations might influence adipocyte differentiation and prove beneficial in the prevention and treatment of obesity.
J Mol Med (Berl) 1996 Jul
PMID:Transcription, adipocyte differentiation, and obesity. 884 47

The aim of the study was to evaluate the effects of cafeteria feeding on the composition of fatty acids in retroperitoneal fat pad and also to determine what happens to fatty acids when rats previously fed the cafeteria diet are returned to regular rat chow. The study of the post-cafeteria rats enabled us to determine the effects of dietary induced excess weight in the absence of artefactual interferences from the diet because these rats, unlike the cafeteria obese rats, ate the same diet as controls. In response to cafeteria feeding there were increases in the majority of adipose tissue fatty acids. However, significant decreases were observed in the relative proportions of 18:2n-6 and in two related n-6 polyunsaturated fatty acids (18:3n-6 and 20:3n-6), as well as in 16:1. In the post-cafeteria obesity model the previous dietary influence on fatty acid composition was still evident. The maintenance of both the high levels and proportions of 18:1 and the decrease of 16:1 percentage in the post-cafeteria rats argues in favour of an alteration in the activity of the elongation metabolic pathway. Certain changes affecting polyunsaturated fatty acid adipose depot composition of obese rats, mainly the decreased levels of 18:2n-6, are long lasting and could be related to the maintenance of the obese status. On the whole, although the fatty acid composition of adipose tissue is influenced by the composition of the diet, there are some differences in both the maintenance of the effects and also in the selectivity of adipose tissue for the different fatty acids of obese and lean rats.
Biochem Mol Biol Int 1996 Oct
PMID:Changes in fatty acid composition in rat adipose tissue induced by dietary obesity. 889 51

The inhibitory action of vanadate towards protein tyrosine phosphatase (PTPase) has been considered as a probable mechanism by which it exerts insulin-like effects. In this study, we have examined the in vivo effects of vanadate on PTPases in the liver of obese Zucker rats, a genetic animal model for obesity and type II diabetes. These animals were characterized by hyperinsulinemia and mild hyperglycemia. The number of insulin receptors were significantly (p < 0.01) decreased in liver. After chronic administration of vanadate in obese rats, 80% decrease in the plasma levels of insulin was observed. The insulin receptor numbers were significantly (p < 0.01) higher in vanadate-treated obese rats as compared to the untreated ones. The hepatic PTPase activities in cytosolic and particulate fractions, with phosphorylated poly glu:tyr (4:1) and the insulin receptor peptide (residues 1142-1153) as substrates, increased in obese rats. In vanadate-treated obese rat livers, the PTPase activities in both subcellular fractions with these substrates decreased significantly (p < 0.001). The decreases in PTPase activities from these groups of rats were further supported by chromatography on a Mono Q column. These data support the view that inhibition of PTPases plays a role in the insulin-mimetic action of vanadate.
Mol Cell Biochem
PMID:Decrease in protein tyrosine phosphatase activities in vanadate-treated obese Zucker (fa/fa) rat liver. 892 27

The effects of vanadate administration on the plasma lipids and hepatic lipogenic enzymes were investigated in Zucker (fa/fa) rat, a model for obesity and non insulin-dependent diabetes. These animals were administered sodium orthovanadate through drinking water for a period of four months. The plasma levels of insulin, triacylglycerols and total cholesterol were significantly (p < 0.001) elevated in untreated obese control rats as compared to the lean animals. In the livers of obese rats, the number of insulin receptors decreased by 60% and the activities of lipogenic enzymes acetyl-CoA carboxylase and ATP-citrate lyase increased by 4.7- and 5.6-folds, respectively. The messenger RNA for ATP-citrate lyase as measured by Northern blot analysis showed a parallel increase in obese control rats. Treatment of these rats with vanadate caused 56-77% decreases in the plasma levels of insulin, triacylglycerols and total cholesterol. The insulin receptor numbers in vanadate-treated obese rats increased (119%) compared to levels in untreated obese animals. The elevated activities of acetyl-CoA carboxylase and ATP-citrate lyase observed in livers of obese rats were significantly reduced by vanadate. The messenger RNA for ATP-citrate lyase also decreased in vanadate-treated obese rats back to the lean control levels. This study demonstrates that vanadate exerts potent actions on lipid metabolism in diabetic animals in addition to the recognized effects on glucose homeostasis.
Mol Cell Biochem
PMID:Vanadate induces normolipidemia and a reduction in the levels of hepatic lipogenic enzymes in obese Zucker rat. 892 41

The ratio of alpha- to beta-receptors is thought to regulate the lipolytic index of adipose depots. To determine whether increasing the activity of the beta 1-adrenergic receptor (AR) in adipose tissue would affect the lipolytic rate or the development of this tissue, we used the enhancer-promoter region of the adipocyte lipid-binding protein (aP2) gene to direct expression of the human beta 1 AR cDNA to adipose tissue. Expression of the transgene was seen only in brown and white adipose tissue. Adipocytes from transgenic mice were more responsive to beta AR agonists than were adipocytes from nontransgenic mice, both in terms of cAMP production and lipolytic rates. Transgenic animals were partially resistant to diet-induced obesity. They had smaller adipose tissue depots than their nontransgenic littermates, reflecting decreased lipid accumulation in their adipocytes. In addition to increasing the lipolytic rate, overexpression of the beta 1 AR induced the abundant appearance of brown fat cells in subcutaneous white adipose tissue. These results demonstrate that the beta 1 AR is involved in both stimulation of lipolysis and the proliferation of brown fat cells in the context of the whole organism. Moreover, it appears that it is the overall beta AR activity, rather than the particular subtype, that controls these phenomena.
Mol Endocrinol 1997 Jan
PMID:Transgenic mice overexpressing the beta 1-adrenergic receptor in adipose tissue are resistant to obesity. 899 85

Lean and obese male Zucker rats were fed high fat (72% of energy as fat), high carbohydrate (66% of energy as carbohydrate) or intermediate diets for 4 weeks commencing 1 week after weaning. We examined the effects of these diets on growth rates, plasma insulin and corticosterone titres, and hypothalamic gene expression of 3 appetite-related neuropeptides. Messenger RNA levels for neuropeptide Y (NPY), galanin (GAL) and corticotropin-releasing factor (CRF) in critical hypothalamic locations were measured by in situ hybridization in each brain. Obese rats grew more rapidly and had elevated plasma insulin and corticosterone concentrations relative to their lean littermates. The obese phenotype was also associated with elevated NPY gene expression in the arcuate nucleus of the hypothalamus and increased GAL gene expression in the hypothalamic paraventricular nucleus. There was no effect of diet on NPY or CRF gene expression in either lean or obese rats. However, maintenance on the high fat diet had a significant effect on GAL gene expression in obese but not lean rats: high fat diet significantly reduced mRNA levels in the obese rats. This reduction in GAL mRNA was accompanied by attenuation of the hyperinsulinemia that is characteristic of this genetic obesity.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Regulation of galanin gene expression in the hypothalamic paraventricular nucleus of the obese Zucker rat by manipulation of dietary macronutrients. 903 34

Interleukin-1 beta (IL-1 beta) induces anorexia when administered acutely or chronically into the cerebrospinal fluid (CSF) at doses that yield estimated pathophysiological concentrations. Enhanced sensitivity to IL-1 beta-induced anorexia has been observed in animal models of obesity, including the obese (fa/fa) Zucker rat. Obesity is also associated with increased tumor necrosis factor-alpha mRNA expression in adipose tissue. This suggests that obese individuals may have dissimilar sensitivity to cytokine action and differential regulation of cytokine production. In this study, we investigated the regulation of the IL-1 beta system (IL-1 beta, IL-1 receptor type I (IL-1RI) and IL-1 receptor antagonist (IL-1Ra)) in the central nervous system (CNS) in response to the chronic intracerebroventricular (i.c.v.) microinfusion (via osmotic minipumps) of 8 ng IL-1 beta/24 h/72 h-a dose that yields estimated pathophysiological concentrations in the CSF. IL-1 beta, IL-1RI and IL-1Ra mRNAs were determined by sensitive RNase protection assays in brain target regions for IL-1 beta (cerebellum, parieto-frontal cortex, hippocampus, hypothalamus and midbrain). The results show that chronic i.c.v. microinfusion of IL-1 beta increased the IL-1 beta mRNA, IL-1R1 mRNA and IL-1Ra mRNA levels in the hypothalamus > cerebellum in both obese (fa/fa) and lean (Fa/Fa) Zucker rats. IL-1 beta mRNA levels also increased in the cortex, hippocampus and midbrain of obese (fa/fa) rats. The profiles of IL-1 beta mRNA, IL-1RI mRNA and IL-1Ra mRNA in the same hypothalamic samples obtained from obese or lean rats were highly intercorrelated. However, no significant differences in the level of IL-1 beta system mRNAs induction were observed in any brain region between obese and lean rats. On the other hand, levels of rat glyceraldehyde 3-phosphate dehydrogenase mRNA were fairly constant, and heat-inactivated IL-1 beta (8 ng/24 h/72 h) had no effect on IL-1 beta, IL-1RI and IL-1Ra mRNAs levels in any brain region. The data suggest: (1) the operation of an IL-1 beta feedback system (IL-1 beta/IL-1Ra/IL-1RI) in brain regions; (2) that enhanced sensitivity of obese rats to IL-1 beta-induced anorexia is not dependent on changes in the brain IL-1 beta system at the mRNA level; and (3) that the present novel approach can be used to investigate the molecular basis of cytokine action in the CNS.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Molecular regulation of the brain interleukin-1 beta system in obese (fa/fa) and lean (Fa/Fa) Zucker rats. 903 35


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