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

Several types of abnormal lipoprotein particles are observed in patients with insulin resistance: elevated VLDL-triglycerides, remnant lipoprotein, small dense LDL, reduced HDL-cholesterol. These patterns are caused by environmental and genetic factors that alter the lipoprotein metabolism. These lipoprotein abnormalities cause insulin resistance through several factors which decrease LPL and PPAR gamma, on the other hand increase ACS and MTP. It is considered that increased plasma level of FFA will closely associated with these factors and their regulations. Secretion of TNF-alpha from adipocytes increases in obesity and closely relates to the pathogenesis of insulin resistance. But the genetic mechanisms are not still clear. More studies about genetic factors which affect to lipoprotein metabolism will be needed and should be considered about the role on insulin resistance.
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PMID:[Molecular mechanism of insulin resistance in hyperlipidemia]. 1063 92

The fat cell, the functional entity of adipose tissue, is mainly involved in energy storage and mobilization. The deposition of fat in, and the mobilization of fat from, adipose tissue are precisely controlled by enzyme activities: LPL and HSL. These functions are under control of hormones such as insulin, catecholamines and, to some extent, steroid hormones. The adipocytes have been recently identified as the source of many factors that may act like hormones either in the local environment or at distant sites, are also target cells for many more hormones. Adipose tissue metabolism varies from one region of the body to another. The metabolic activity is the lowest in the subcutaneous gluteofemoral area, followed by the abdominal subcutaneous area, and the highest in the visceral region. The metabolic activity of gluteofemoral fat is activated in lactating mothers. Body fat content changes with female age. Puberty, parity and menopause seems to increase accretion of adipose tissue. Obesity is defined as an increase in body fat content. There is general agreement that obesity develops as an interaction between a genetic susceptibility and environment which is expressed when the subject is exposed to a certain set of environmental conditions. Obesity develops when energy intake exceeds energy expenditure over a prolonged period. Excess body weight is associated with several diseases which can shorten life expectancy. The prevalence of obesity is high and increases steadily. Approximately 20-40% of women are overweight (BMI 25-30 kg/m-2) and 5-20% are obese (BMI > 30 kg/m-2).
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PMID:[Pathophysiological aspects of adipose tissue development in women]. 1089 89

Obesity is a chronic metabolic disorder associated with CVD and increased morbidity and mortality. When the BMI is > or = 30 kg/m2, mortality rates from all causes, and especially CVD, are increased by 50% to 100%. There is strong evidence that weight loss in overweight and obese individuals improves risk factors for diabetes and CVD. Additional evidence indicates that weight loss and the associated diuresis reduce blood pressure in both overweight hypertensive and nonhypertensive individuals, reduce serum TG levels, increase high-density lipoprotein cholesterol levels, and may produce some reduction in low-density lipoprotein cholesterol concentrations. Of interest, even if weight loss is minimal, obese individuals showing a good level of cardiorespiratory fitness are at reduced risk for cardiovascular mortality than lean but poorly fit subjects. Insulin and catecholamines have pronounced metabolic effects on human adipose tissue metabolism. Insulin stimulates LPL and inhibits HSL; the opposite is true for catecholamines. There is regional variation in adipocyte TG turnover favoring lipid mobilization in the visceral fat depots and lipid storage in the peripheral subcutaneous sites. The hormonal regulation of adipocyte TG turnover is altered in obesity and is most marked in central obesity. There is resistance to insulin stimulation of LPL; however, LPL activity in fasted obese subjects is increased and remains so following weight reduction. Catecholamine-induced lipolysis is enhanced in visceral fat but decreased in subcutaneous fat. Numerous adaptive responses take place with physical training. These adaptations result in a more efficient system for oxygen transfer to muscle, which is now able to better utilize the unlimited lipid stores instead of the limited carbohydrate reserves available. In addition, the reduced adipose tissue mass represents an important mechanical advantage, allowing better long-term work. Gender differences have been reported in the adaptation of adipose tissue metabolism to aerobic exercise training. Physical training helps counteract the permissive and affluent environment that predisposes reduced-obese subjects to regain weight. An exercise program using weight resistance modalities may also be included safely, and it improved program retention in a multidisciplinary weight management program that was designed for obese children. Thirty to 45 minutes of physical activity of moderate intensity, performed 3 to 5 days a week, should be encouraged. All adults should set a long-term goal to accumulate at least 30 minutes or more of moderate-intensity physical activity on most, and preferably all days. Public health interventions promoting walking are likely to be the most successful. Indeed, walking is unique because of its safety, accessibility, and popularity. It is noteworthy that there is a clear dissociation between the adaptation of cardiorespiratory fitness and the improvements in the metabolic risk profile that can be induced by endurance training programs. It appears that as long as the increase in energy expenditure is sufficient, low-intensity endurance exercise is likely to generate beneficial metabolic effects that would be essentially similar to those produced by high-intensity exercise. The clinician should therefore focus on the improvement of the metabolic profile rather than on weight loss alone. Realistic goals should be set between the clinician and the patient, with a weight loss of approximately of 0.5 to 1 pound per week. It should be kept in mind that since it generally takes years to become overweight or obese, a weight loss pattern of 0.5 or 1 pound per week will require time and perseverance to reach the proposed target. However, the use of physical activity as a method to lose weight seems inversely related to patients' age and BMI and directly related to the level of education. Thus, public health interventions helping these groups to become physically active remain a challenge and further emphasize the importance of the one-on-one interaction between the clinician/health care professional with the obese individual "at risk" of CVD. This notion is critical, as it has been shown that less than half of obese adults have reported being advised to lose weight under the guidance of health care professionals.
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PMID:Exercise in weight management of obesity. 1157 Jan 17

We studied 4,058 subjects from a representative sample of the Singapore population 1) to determine the association between the S447X polymorphism at the LPL locus and serum lipid concentration in Chinese, Malays, and Asian Indians living in Singapore and 2) to explore any interactions with apolipoprotein E (APOE) genotype, exercise, obesity, cigarette smoking, and alcohol intake. Information on obesity, lifestyle factors (including smoking, alcohol consumption, and exercise frequency), glucose tolerance, and fasting lipids was obtained. Male and female carriers of the X447 allele had lower serum triglyceride concentrations and higher HDL cholesterol (HDL-C) concentrations. The association between the X447 allele and serum HDL-C concentration was modulated by APOE genotype in males and cigarette smoking and alcohol intake in females. The effect of the X447 allele was greatest in men who carried the E4 allele and women who smoked or consumed alcohol. The X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Interactions with APOE genotype, cigarette smoking, and alcohol intake reinforce the importance of examining genetic associations, such as this one, in the context of the population of interest.
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PMID:The lipoprotein lipase S447X polymorphism and plasma lipids: interactions with APOE polymorphisms, smoking, and alcohol consumption. 1506 87

We examined the expression and activity of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in abdominal adipose tissue in women. This recently characterized enzyme from the aldoketoreductase 1C family is responsible for the conversion of progesterone into 20alpha-hydroxyprogesterone. Abdominal sc (SC) and omental (OM) adipose tissue biopsies were obtained from a sample of 32 women aged 47.7 +/- 5.9 yr (body mass index 27.6 +/- 5.0 kg/m(2)) undergoing abdominal hysterectomies. Body composition and body fat distribution measurements were performed before the surgery by dual-energy x-ray absorptiometry and computed tomography, respectively. The expression of 20alpha-HSD was determined by real-time RT-PCR, and its activity was measured in whole-tissue homogenates. mRNA and activity of the enzyme were detected in both the SC and OM fat depots, the two measures being significantly higher in the SC compartment. Women characterized by a visceral adipose tissue area of 100 cm(2) or greater had an increased 20alpha-HSD conversion rate in their OM adipose tissue, compared with women without visceral obesity (13.99 +/- 2.07 vs. 7.92 +/- 0.83 fmol/microg protein per 24 h, P < 0.05). Accordingly, a positive correlation was found between OM adipose tissue 20alpha-HSD activity and computed tomography-measured visceral adipose tissue area (r = 0.36, P < 0.05). Significant positive correlations were also found between OM 20alpha-HSD activity and OM adipocyte diameter (r = 0.49, P < 0.05) and OM adipose tissue LPL activity (r = 0.36, P = 0.06). In conclusion, 20alpha-HSD activity and mRNA were detected in SC and OM adipose tissue in women, and OM 20alpha-hydroxylation of progesterone was highest in women with visceral obesity. Additional studies are required to establish whether local conversion of progesterone may impact on the metabolism and function of adipocytes located within the abdominal cavity.
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PMID:Expression and activity of 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in abdominal subcutaneous and omental adipose tissue in women. 1549 62

We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha-HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal subcutaneous and omental adipose tissue biopsies were obtained during abdominal hysterectomies in seven women with low visceral adipose tissue (VAT) area and seven age- and total body fat mass-matched women with visceral obesity. Women with elevated VAT areas were characterized by significantly higher omental adipose tissue 20alpha-HSD and 3alpha-HSD-3 mRNA abundance compared with women with low VAT accumulations (1.4- and 1.6-fold differences, respectively; P < 0.05). Omental and subcutaneous adipose tissue 3alpha-HSD activities were significantly higher in women with high vs. low VAT areas (P < 0.05 for both comparisons). Total and visceral adiposities were positively associated with omental 20alpha-HSD mRNA level (r = 0.75, P < 0.003 for fat mass; r = 0.57, P < 0.04 for VAT area) and omental 3alpha-HSD-3 mRNA level (r = 0.68, P < 0.01 for fat mass; r = 0.74, P < 0.003 for VAT area). Enzyme activities in both depots were also positively correlated with adiposity measures. Omental adipose tissue enzyme expression and activity were positively associated with omental adipocyte size and LPL activity. In conclusion, mRNA abundance and activity of AKR1C enzymes in abdominal adipose tissue compartments are positive correlates of adiposity in women. Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact locally on fat cell metabolism.
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PMID:Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women. 1549 12

Fenofibrate, a selective (1)PPAR-alpha activator, is prescribed to treat human dyslipidemia. The aim of this study was to delineate the mechanism of fenofibrate-mediated reductions in adiposity, improvements in insulin sensitivity, and lowering of triglycerides (TG) and free fatty acids (FFA) and to investigate if these favorable changes are related to the inhibition of lipid deposition in the aorta. To test this hypothesis we used male LDLr deficient mice that exhibit the clinical features of metabolic syndrome X when fed a high fat high cholesterol (HF) diet. LDLr deficient mice fed HF diet and simultaneously treated with fenofibrate (100 mg/kg body weight) prevented development of obesity, lowered serum triglycerides and cholesterol, improved insulin sensitivity, and prevented accumulation of lipids in the aorta. Lowering of circulating lipids occurred via down-regulation of lipogenic genes, including fatty acid synthase, acetyl CoA carboxylase and diacyl glycerol acyl transferase-2, concomitant with decreased liver TG and cholesterol, and TG output rate. Fenofibrate also suppressed liver apoCIII mRNA levels and markedly increased lipoprotein lipase mRNA levels, known to enhance serum TG catabolism. In addition, fenofibrate profoundly reduced epididymal fat and mesenteric fat mass to the levels seen in lean mice. The reductions in body weight were associated with elevation of hepatic uncoupling protein 2 (UCP2) mRNA, a concomitant increase in the ketone body formation, and improved insulin sensitivity associated with tumor necrosis factor-alpha reductions and phosphoenol pyruvate carboxykinase down-regulation. These results demonstrate that fenofibrate improves lipid abnormalities partly via inhibition of TG production and partly via clearance of TG-rich apoB particles by elevating LPL and reduced apoCIII. The prevention of obesity development occurred via energy expenditure. Fenofibrate-mediated hypolipidemic effects together with improved insulin sensitivity and loss of adiposity led to the reductions in the aortic lipid deposition by inhibiting early stages of atherosclerosis possibly via vascular cell adhesion molecule-1 (VCAM-1) modulation. These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X.
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PMID:Peroxisome proliferator-activated receptor-alpha selective ligand reduces adiposity, improves insulin sensitivity and inhibits atherosclerosis in LDL receptor-deficient mice. 1647 80

In this study, we examined whether the increased availability of lipids in blood resulting from two types of diet manipulation regulated metabolic gene expression in the skeletal muscle of rats. Feeding for 4 wk on an isocaloric-sucrose or a hypercaloric-fat diet increased plasma TAG in the fed condition by increments of 70 and 40%, respectively, and increased fasting insulinemia (approximately 3-fold) compared with a starch diet. The fat diet impaired glucose tolerance and caused obesity, whereas sucrose-fed rats maintained their normal weight. We analyzed the expression of genes that regulate the exogenous FA supply (LPL, FAT/CD36, FATP1), synthesis (ACC1), glucose (GLUT4, GLUT1, HK2, GFAT1, glycogen phosphorylase) or glycerol (glycerol kinase) provision, or substrate choice for oxidation (PDK4) in gastrocnemius and soleus muscles at the end of the glucose tolerance test. LPL, FAT/CD36, FATP1, PDK4, and GLUT4 mRNA as well as glycogen phosphorylase and glycerol kinase activity levels in both muscles were unchanged by the diets. Increased mRNA levels of GLUT1 (1.6- and 2.6-fold, respectively) and GFAT1 (about 1.7-fold) in gastrocnemius, and of ACC1 (about 1.5-fold) in soleus, were found in both the sucrose and fat groups. In the fat group, HK2 mRNA was also higher (1.8-fold) in the gastrocnemius. Both sucrose and saturated-fat diets prompted hyperinsulinemia and hyperlipemia in rats. These metabolic disturbances did not alter the expression of LPL, FAT/CD36, FATP1, PDK4, and GLUT4 genes or glycogen phosphorylase and glycerol kinase activity levels in either analyzed muscle. Instead, they were linked to the coordinated upregulation in gastrocnemius of genes that govern glucose uptake and the hexosamine pathway, namely, GLUT1 and GFAT1, which might contribute to insulin resistance.
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PMID:Effect of sucrose and saturated-fat diets on mRNA levels of genes limiting muscle fatty acid and glucose supply in rats. 1655 72

Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity. We generate and analyse a list of nine primary candidate genes for T2D genes and five for obesity. Two genes, LPL and BCKDHA, are common to these two sets. We also present a set of secondary candidates for T2D (94 genes) and for obesity (116 genes) with 58 genes in common to both diseases.
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PMID:Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes. 1675 74

Lipoprotein lipase mass in preheparin serum (preheparin LPL mass) is assumed to reflect some of the LPL production in the whole body and insulin sensitivity. While metabolic syndrome is a common underlying condition for cardiovascular diseases, biological marker of this syndrome has not been fully established. To clarify the characteristics of preheparin LPL mass in metabolic syndrome, 362 Japanese subjects were studied to examine the relationship between symptoms of metabolic syndrome and preheparin LPL mass and compare with plasma adiponectin. Furthermore the relation with urinary 8-hydroxydeoxyguanosine (8-OHdG) that reflects oxidative stress to DNA was also studied. Both preheparin LPL mass and plasma adiponectin correlated positively with HDL-cholesterol and negatively with body weight and triglyceride. Only preheparin LPL mass showed a negative correlation with fasting blood glucose and HbA1c. Both mean preheparin LPL mass and plasma adiponectin decreased with an increase in severity of the metabolic syndrome with/without obesity and with/without diabetes. The correlation coefficient between preheparin LPL mass and plasma adiponectin was r=0.562. A negative correlation between preheparin LPL mass and urinary 8-OHdG was observed. These results suggest that low preheparin LPL mass may reflect systemic oxidative stress and also a biomarker of the severity of metabolic syndrome.
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PMID:Preheparin serum lipoprotein lipase mass might be a biomarker of metabolic syndrome. 1695 92


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