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

To achieve a better understanding of the biochemical basis of obesity, we have undertaken comparative analyses of adipose tissue of lean and obese mice. By two-dimensional gel analysis, carbonic anhydrase-III (CA III) has been identified as a major constituent of murine adipose tissue. Quantitative comparisons of CA III protein and mRNA levels indicate that this enzyme is expressed at lower levels in adipose tissue from animals that were either genetically obese or had experimentally induced obesity compared to levels in the corresponding lean controls. This decrease in CA III expression was unique to adipose tissue, since other CA III-containing organs and tissues did not show a change when lean and obese animals were compared. Additionally, levels of CA III in adipose tissue from obese animals responded to acute changes in energy balance of the animal. These results are discussed in light of possible metabolic roles for CA III.
Mol Endocrinol 1991 Jun
PMID:Expression of CA III in rodent models of obesity. 192

Cytochrome P450IIE1 (IIE1) is a microsomal xenobiotic-activating enzyme that is inducible not only by various chemical agents but also by fasting and diabetes. Using a rat model that mimics human obesity, we have found that hepatic IIE1 levels are also increased by this common clinical disorder. Liver microsomes from rats made obese by feeding with an energy-dense diet displayed elevated aggregate P450 content (+28%) and enhanced catalytic activities associated with IIE1, including low-Km N-nitrosodimethylamine demethylation (+66%), aniline hydroxylation (+52%), p-nitrophenol hydroxylation (+170%), and acetaminophen-cysteine conjugate formation (+28%). In contrast, obesity had no significant effect on cytochrome b5 content, P450 reductase activity, benzphetamine demethylation, or erythromycin demethylation, with the latter two reactions being linked with rat IIC11 and IIIA1, respectively. The enhancement of IIE1-dependent drug-metabolizing activities noted in liver microsomes from obese rats was paralleled by a similar increase (111%) in hepatic IIE1 protein content in these animals, as assessed on immunoblots developed with anti-hamster IIE1 IgG. Anti-IIE1-inhibitable rates of microsomal p-nitrophenol metabolism, a reaction highly correlated with IIE1 content (r = 0.88, p less than 0.01), were over 3-fold higher in obese rats than in nonobese controls, providing additional evidence for the obesity-related increase of hepatic IIE1. The induction of IIE1 by the pathophysiological condition of obesity may provide a biochemical basis for the increased incidence of occult liver disease and certain cancers noted in obese individuals.
Mol Pharmacol 1991 Mar
PMID:Induction of cytochrome P450IIE1 in the obese overfed rat. 200 76

Binding equilibria of valproate (2-n-propyl-pentanoic acid anion) with defatted human serum albumin were studied by equilibrium dialysis in a 66 mM sodium phosphate buffer, pH 7.4, 37 degrees. Three hundred and fifty-six observed points for bound versus free valproate concentration were obtained and analyzed in terms of stepwise binding. It was found that the best fit resulted from a model in which 67% of the albumin was capable of binding valproate, whereas 33% did not bind. Thirty acceptable variants of the curve fitting were generated in order to assess the variation of the binding constants. The binding albumin component combines with three molecules of valproate with high affinity and with at least seven additional molecules that are loosely bound. Saturation of the protein cannot be reached. At very high concentrations of free valproate (above 10 mM) irreversible changes in the albumin take place, resulting in poor reproducibility in the amount of bound valproate. In the presence of palmitate, 0.5, 1, and 1.5 mol/mol of albumin, binding of valproate is decreased by a competitive mechanism. It is hypothesized that obesity, developing as a complication of valproate treatment of epilepsy, results from increased availability of long-chain fatty acids due to competitive valproate binding.
Mol Pharmacol 1990 May
PMID:Valproate and palmitate binding to human serum albumin: an hypothesis on obesity. 211 Oct 5

beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
Mol Cell Endocrinol 1990 Jul 09
PMID:Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue. 221 32

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), has been isolated and characterized because of its enterogastrone-type effects. It is also named glucose-dependent insulinotropic polypeptide and is actually considered to be the main incretin factor of the entero-insular axis. Besides these well-described effects on gastric secretion and pancreatic beta cells, it also has direct metabolic effects on other tissues and organs, such as adipose tissue, liver, muscle, gastrointestinal tract and brain. In adipose tissue it is involved in the activation and regulation of lipoprotein lipase (LPL); it also inhibits glucagon-induced lipolysis and potentiates the effect of insulin on incorporation of fatty acids into triglycerides. It may play a role in the development of obesity because of the hypersensitivity of adipose tissue of obese animals to some of these actions. In the liver it does not modify insulin extraction, and its incretin effects are due only to the stimulation of insulin secretion and synthesis. It reduces hepatic glucose output and inhibits glucagon-stimulated glycogenolysis. It might increase glucose utilization in peripheral tissues such as muscle. GIP also has an effect on the volume and/or electrolyte composition of intestinal secretion and saliva. The functional importance of its effect on the hormones of the anterior pituitary lobe remains to be established, as it has never been detected in the brain. Its links with insulin are very close and the presence of insulin is sometimes necessary for the greater efficiency of both hormones. GIP can be considered as a true metabolic hormone, with most of its functions tending to increase anabolism.
J Mol Endocrinol 1989 May
PMID:Gastric inhibitory polypeptide: a gut hormone with anabolic functions. 266 79

The secretion of growth hormone (GH) is abnormal in genetically obese Zucker rats. Measurements of pulsatile GH release and circulating GH levels in lean (Fa/?) and obese (fa/fa) rats have shown that both are reduced in the latter. We have studied pituitary GH gene expression in order to understand the role of GH synthesis in this abnormality. Obese animals have lower pituitary GH mRNA levels than lean controls. Within each genotype a sex difference was observed with the female animals having lower GH mRNA levels than the males. It is unlikely that the GH abnormality is due to a generalized pituitary defect because prolactin mRNA levels were the same in all four groups of rats.
Mol Cell Endocrinol 1989 Aug
PMID:Obesity- and sex-related alterations in growth hormone messenger RNA levels. 277 63

Adenylate cyclase activity and its modulation by guanine nucleotides and isoproterenol were assessed in adipocyte membranes of mice with mutations causing different genetic obesity syndromes. The object was to determine whether the defect in inhibitory modulation observed in the obese (ob/ob) mouse was also present in the diabetes (db/db) mouse. The data show that adipocyte adenylate cyclase in both the ob/ob and the db/db mouse is resistant to activation by isoproterenol. The response to guanosine triphosphate (GTP) differed between the two mutants, such that an inhibitory phase was visible in the db/db but not in the ob/ob membranes. Moreover, pertussis toxin attenuated the inhibitory effect of GTP and significantly stimulated cyclase activity in the db/db but not in the ob/ob membranes. The data show that the two mutations affect the expression of adenylate cyclase activity via different mechanisms.
Mol Cell Endocrinol 1988 Oct
PMID:Effect of the genetic background and specific mutation on adenylate cyclase activity in obesity syndromes. 318 20

Hepatic plasma membranes of female obese mice C57 BL-6 orl ob/ob (ob/ob mice) completely lack vasopressin (VP) receptors of the V1 type whereas kidney VP receptors are normally expressed and functionally coupled to adenylate cyclase. To discover if these alterations are linked to a genetic defect of the V1 receptor, we have studied the binding of VP on liver and kidney membranes of two other models, female diabetic mice C57 BL-6 orl db/db (db/db mice) and female Zucker rats Fatty/orl fa/fa (fa/fa rats), which exhibit different temporal pattern of obesity, hyperinsulinemia and insulin resistance. In addition, since VP is known to exert its vascular response through stimulation of V1 receptors, we have studied the reactivity of VP of isolated tail artery in the three different models, ob/ob and db/db mice and fa/fa rats, and in their respective controls. In all cases, VP kidney receptors and VP vascular reactivity are normal. db/db mice exhibit a marked decrease in hepatic VP receptors whereas a 50% decrease was observed in 32 week fa/fa rats. Angiotensin II and prazosin binding sites are still present as well as the adenylate cyclase response to glucagon. These results suggest that the specific alteration in liver VP receptors is not related to a defect in V1 receptor genetic expression but is specific for liver and appears to parallel the level of hyperinsulinemia and/or insulin resistance.
Mol Cell Endocrinol 1984 Dec
PMID:Reduction in hepatic but not in renal and vascular vasopressin receptor number in hyperinsulinemic mice and rats. 609 84

The B-L region of the chicken major histocompatibility complex (MHC), the so-called B-locus, corresponds to the murine H-2 I-region. Using alloantibodies and monoclonal antibodies to B-L we analyzed: (a) the tissue distribution of B-L+ cells, (b) the function of B-L+ cells, and (c) the possible role of B-L+ cells in the development of spontaneous autoimmune thyroiditis (SAT) in Obese strain (OS) chickens. The tissue distribution of B-L+ cells in peripheral blood and various lymphoid and nonlymphoid organs corresponds to what is known for mammals. In the bursa of Fabricius most lymphoid cells and the dendritic cells carry the B-L antigen; B-L+ thymic nurse cells (TNC) first appear on day 17 of embryonic life; chickens possess dendritic B-L+ cells in the skin resembling mammalian Langerhans cells; in addition we found that the microglia is unequivocally B-L+. B-L+ peripheral blood lymphocytes (PBL) were separated with a fluorescence-activated cell sorter. Ten percent of unstimulated PBL and 60% of phytohemagglutinin (PHA) stimulated T-cell blasts are B-L+. In graft-vs-host (GvH) assays B-L- cells were identified as the effector cells. These cells respond to PHA and concanavalin A (Con A), but not to pokeweed mitogen (PWM). B-L+ cells cannot be stimulated by Con A and PHA, but respond to PWM. They possess only a very low activity in GvH assays which can be inhibited by anti-T-cell sera. In OS chickens B-L+/non-B/, non-T and B-L+ T (blasts?) cells are found in the "first line" of mononuclear cell infiltration in the thyroid glands. Most interesting, thyroid epithelial cells--which are normally B-L- -become B-L+ in the neighbourhood of B-L+ infiltrating mononuclear cells. This observation may be of significance for autoantigen presentation and perpetuation in autoimmune thyroiditis. Finally, OS thymuses contain significantly less TNC than normal controls.
Mol Immunol 1984 Dec
PMID:Distribution and functional analysis of B-L/Ia-positive cells in the chicken: expression of B-L/Ia antigens on thyroid epithelial cells in spontaneous autoimmune thyroiditis. 644 Nov 16

Glucagon has been shown to lower blood lipids and to decrease food intake and body weight in short-term studies in man and animals. There is evidence of decreased secretion of glucagon in human obesity. The Zucker obese rat suffers from a genetic type of obesity and has an absolute reduction in circulating glucagon concentration. The effect of long-term administration of glucagon on the body weight in obese Zucker rats was studied. Glucagon caused a marked (-20%) reduction of body weight in obese Zucker rats with no change in feed intake. Urine glucose, urea nitrogen, creatinine, and ketone content, as well as serum triglyceride, cholesterol, alkaline phosphatase, creatinine, and insulin levels remained unchanged. Weights of perirenal fat, kidneys, and heart also remained unchanged. However, glucagon injection in obese Zucker rats caused significant decrease in serum glucose, and increases in SGOT, liver weight, and liver lipid and glycogen content. Further investigations are needed concerning the safety of chronic glucagon administration for weight control.
Exp Mol Pathol 1984 Jun
PMID:Suppression of weight gain by glucagon in obese Zucker rats. 672 36


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