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)

We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol.
 ...
PMID:Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats? 151 9

Inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia in humans. This class of therapeutic agents, in addition to lowering plasma cholesterol, reduces plasma triglyceride levels. We have investigated the mechanism of triglyceride-lowering effect of lovastatin in the hypertriglyceridemic state by using a rodent model of hypertriglyceridemia and obesity, the Zucker obese (fa/fa) rat. Lovastatin treatment (4 mg/kg), as compared to placebo, caused a 338% reduction in plasma triglyceride (146 +/- 5 vs. 494 +/- 76 mg/dl), a 58% decrease in total cholesterol (99 +/- 13 vs. 156 +/- 18 mg/dl), and a 67% reduction in high density lipoprotein (HDL)-cholesterol (69 +/- 8 vs. 115 +/- 15 mg/dl). The fall seen in plasma triglyceride was due to a decrease in hepatic secretion of very low density lipoproteins (VLDL), determined after blocking the clearance of triglyceride-rich lipoproteins with Triton WR-1339. Lovastatin treatment did not affect either the activities of hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, or malic enzyme, or the activities of the lipolytic enzymes of adipose tissue, lipoprotein lipase, or liver, hepatic triglyceride lipase. Supplementation of mevalonolactone in the diet partially reversed the changes in plasma triglyceride (265 +/- 37 vs. 146 +/- 5 mg/dl), but not in total or HDL-cholesterol. These data demonstrate that, in the hypertriglyceridemic Zucker rat model, HMG-CoA reductase inhibitors reduce the rate of secretion of VLDL and this effect can be partially reversed by administration of mevalonolactone.
 ...
PMID:Mechanisms of triglyceride-lowering effect of an HMG-CoA reductase inhibitor in a hypertriglyceridemic animal model, the Zucker obese rat. 155 26

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.
 ...
PMID:Induction of cytochrome P450IIE1 in the obese overfed rat. 200 76

Our studies show that obese women with polycystic ovary syndrome are more likely to have hirsutism and menstrual disturbances than are lean women with PCOS. The most obvious biochemical differences between obese and lean women with PCOS is that SHBG concentrations are much lower in women with obesity. The SHBG levels are inversely related to insulin, and insulin has been shown to have a direct inhibitory action on SHBG secretion. Other factors, however, may contribute to the mechanism of the increased prevalence of hirsutism and anovulation in obese women with PCOS, such as a direct effect of insulin or increased activity of 5 alpha-reductase in peripheral tissues. Finally we have been able to show that weight reduction of more than 5% is associated with an improved biochemical profile and, importantly, with restoration of fertility.
 ...
PMID:Obesity and polycystic ovary syndrome. 205 54

Two hundred and sixty-three women with ultrasound-diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI greater than 25 kg/m2). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non-obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5 alpha-reductase activity, were higher in obese than in non-obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8-h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio-availability of androgens to peripheral tissues and enhanced activity of 5 alpha-reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.
 ...
PMID:Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: an analysis of 263 consecutive cases. 211 67

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
 ...
PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

We aim to evaluate the effects of phenobarbital (PB) on the liver drug metabolism, NADPH production capacity and terminal gluconeogenic enzyme, glucose-6-phosphatase (G6Pase) activity in the diabetic state associated with genetic obesity in mice. The results showed that PB treatment increased the amount of liver total cytochrome P450 (cytP450), a drug metabolizing monooxygenase enzyme in genetically obese, hyperglycemic (ob/ob) mice 6-fold and the total activities of other monooxygenase enzymes NADPH cytP450 reductase and 7-ethoxyresorufin O-deethylase (ERDE) 2- and 6.5-fold, respectively. In addition, the regimen increased the liver total activities of two NADPH generating enzymes, 6-phosphogluconate dehydrogenase (6PGDH) and malic enzyme (ME) in obese mice suggesting that the regimen enhanced liver NADPH production capacity in the animals. The data further showed that PB treatment decreased the high hepatic G6Pase activity in obese mice. Both enhanced NADPH generating enzyme activities and lowered G6Pase activity may suppress hepatic glucose output. Since NADPH is required for drug oxidation reactions as a reducing cofactor, high NADPH generating capacity may facilitate liver drug metabolism in vivo. Although the diabetic state in obese mice differs somewhat from that seen in non-insulin dependent diabetic subjects (NIDDs), these findings provide some knowledge about the possible biochemical mechanisms whereby PB treatment normalizes drug metabolism and glycemic control in NIDDs, as has been noted in previous studies.
 ...
PMID:Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice. 283 24

Hydroxymethylglutaryl coenzyme A reductase (HMGR) activity is a major factor in the regulation of cholesterol homeostasis. Enzyme activity is known to vary with age, sex, diurnal cycle, and dietary properties in rats. Mice are available in numerous genetic strains and could be a useful inexpensive animal model for studying diet and genetic interactions in the regulation of cholesterol metabolism. Obese and non-obese C57BL/6J, CBA/J, and obese and non-obese DW dbPas mice were subjected to variations in light cycle, feeding schedule, and pectin and fat composition of their diets. They were then killed by decapitation, and hepatic microsomal HMGR analyzed. The mice responded in the same ways as rats to light cycle, feeding pattern, and sex difference. They exhibited marked differences in HMGR activity due to age, genotype, strain, and diet variations. We conclude that mice will, indeed, offer an excellent animal model for the study of cholesterol metabolism regulation.
 ...
PMID:Hepatic hydroxymethylglutaryl coenzyme A reductase activity in inbred strains of mice. 323 19

The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO2, but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO2 or in incorporation into lipid (both soleus and EDL muscles), except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform changes in metabolism between muscles of the obese rats.
 ...
PMID:Metabolic characteristics of skeletal muscle from lean and obese Zucker rats. 345 May 49

Temporal and spatial patterns of lipid deposition, vascularization and collagen deposition were described for subcutaneous adipose tissue in the fetal pig. Enzyme cytochemical changes were reported as they relate to the morphological differentiation of the subcutaneous depot. There are distinct temporal lags between the appearance of specific enzymes in adipocytes. For example, NADH-tetrazolium reductase activity appeared earliest whereas esterase activity appeared before lipoprotein lipase (LPL) activity. Adipose tissue primordia has been localized around specific tissue components in rat and pig tissues. These tissue components include hair follicles, sweat glands, large nerves, large blood vessels and mammary gland ducts. Lipid and enzyme cytochemistry demonstrates physical continuity between primordial cells and differentiated fat cell clusters. Alterations in maternal and/or fetal endocrine or metabolic profiles result in specific changes in fetal subcutaneous adipocytes. For example, maternal diabetes significantly increases cell size whereas genetic obesity has little effect on cell size but increases cellular LPL activity significantly. A comparison of subcutaneous and perirenal depots in the pig fetus indicated several depot specific anatomical and enzyme histochemical traits. Blood vessel architecture and vascular alkaline phosphatase activity clearly demarcated perirenal and subcutaneous depots in the fetus. These data indicate that site to site variations of adipose tissue characteristics may be reflecting intrinsic stromal-vascular aspects of specific locations.
 ...
PMID:Anatomical and enzyme histochemical differentiation of adipose tissue. 393 90


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