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

The effects of long-term endurance exercise training, body composition, and cardiovascular fitness (VO2max) on the activity of adipose tissue lipoprotein lipase (AT-LPL) and lipoprotein lipids were examined in 66 healthy age-matched middle-aged and older men (mean +/- SE, 61 +/- 1 years). We compared subcutaneous abdominal (ABD) and gluteal (GLT) heparin-elutable AT-LPL activity in 19 master athletes (VO2max > 40 mL/kg/min) and 20 lean sedentary men (VO2max < 40 mL/kg/min) versus 27 obese sedentary men (VO2max < 40 mL/kg/min; body fat > 27%). Fasting insulin and leptin levels were similar in master athletes and lean sedentary men, but were lower than in obese sedentary men. There were no differences in fasting values for total cholesterol or low-density lipoprotein cholesterol (LDL-C) among the groups, but master athletes had lower triglyceride (TG) values (P < .05) and higher high-density lipoprotein cholesterol (HDL-C) and HDL2-C (P < .05) than obese and lean sedentary men. There were no regional (ABD v GLT) differences in the activity of AT-LPL in these groups, but obese sedentary men had higher levels of ABD AT-LPL (2.1 +/- 0.3 nmol/10(6) cells x min) than lean sedentary men (0.8 +/- 0.2) and master athletes (0.5 +/- 0.1, P = .01). Similar results were observed for GLT AT-LPL. Both ABD and GLT AT-LPL activity correlated positively with percent body fat (r = .46 to .54, P < .001), fasting insulin (r = .37 to .45, P < .001), and leptin (r = .61 to .65, P < .0001), but not with VO2max. In stepwise multiple regression analysis, leptin was the main independent predictor of ABD (R2 = .43, P < .0001) and GLT (R2 = .40, P < .0001) AT-LPL activity. Plasma TG correlated positively (r = .32, P < .01) and HDL-C correlated negatively (r = -.32, P = .02) with ABD AT-LPL activity, but these relationships were not significant after controlling for percent body fat or leptin. The results of this study indicate that in healthy middle-aged and older men, the major determinants of AT-LPL activity are obesity and its major associated hormones, leptin and insulin, not cardiovascular fitness, and also suggest that the higher HDL-C levels observed in endurance-trained men are not associated with increased AT-LPL activity.
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PMID:Predictors of adipose tissue lipoprotein lipase in middle-aged and older men: relationship to leptin and obesity, but not cardiovascular fitness. 1002 79

Type 2 diabetes mellitus and obesity are characterized by fasting hyperinsulinemia, insulin resistance with respect to glucose metabolism, elevated plasma free fatty acid (FFA) levels, hypertriglyceridemia, and decreased high-density lipoprotein (HDL) cholesterol. An association between hyperinsulinemia and dyslipidemia has been suggested, but the causality of the relationship remains uncertain. Therefore, we infused eight 12-week-old male catheterized conscious normal rats with insulin (1 mU/min) for 7 days while maintaining euglycemia using a modification of the glucose clamp technique. Control rats (n = 8) received vehicle infusion. Baseline FFAs were 1.07+/-0.13 mmol/L, decreased to 0.57+/-0.10 (P < .05) upon initiation of the insulin infusion, and gradually increased to 0.95+/-0.12 by day 7 (P = NS vbaseline). On day 7 after a 6-hour fast, plasma insulin, glucose, and FFA levels in control and chronically hyperinsulinemic rats were 32+/-5 versus 116+/-21 mU/L (P < .005), 122+/-4 versus 129+/-8 mg/dL (P = NS), and 1.13+/-0.18 versus 0.95+/-0.12 mmol/L (P = NS); total plasma triglyceride and cholesterol levels were 78+/-7 versus 66+/-9 mg/dL (P = NS) and 50+/-3 versus 47+/-2 mg/dL (P = NS), respectively. Very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and HDL2 and HDL3 subfractions of plasma triglyceride and cholesterol were similar in control and hyperinsulinemic rats. Plasma FFA correlated positively with total (r = .61, P < .005) triglycerides. On day 7 after an 8-hour fast, hyperinsulinemic-euglycemic clamps with 3-3H-glucose infusion were performed in all rats. Chronically hyperinsulinemic rats showed peripheral insulin resistance (glucose uptake, 15.8+/-0.8 v 19.3+/-1.4 mg/kg x min, P < .02) but normal suppression of hepatic glucose production (HGP) compared with control rats (4.3+/-1.0 v 5.6+/-1.4 mg/kg x min, P = NS). De novo tissue lipogenesis (3-3H-glucose incorporation into lipids) was increased in chronically hyperinsulinemic versus control rats (0.90+/-0.10 v 0.44+/-0.08 mg/kg x min, P < .005). In conclusion, chronic physiologic hyperinsulinemia (1) causes insulin resistance with regard to the suppression of plasma FFA levels and increases lipogenesis; (2) induces peripheral but not hepatic insulin resistance with respect to glucose metabolism; and (3) does not cause an elevation in VLDL-triglyceride or a reduction in HDL-cholesterol.
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PMID:Chronic physiologic hyperinsulinemia impairs suppression of plasma free fatty acids and increases de novo lipogenesis but does not cause dyslipidemia in conscious normal rats. 1009 9

Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published results have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo A1/HDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.
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PMID:Lipoprotein alterations, abdominal fat distribution and breast cancer. 1031 21

Lower-body obesity is associated with a lower incidence of diabetes and high values of HDL2 cholesterol and thus seems to have a metabolic profile opposite to upper-body obesity. We measured insulin sensitivity by the minimal model procedure in 20 lower-body overweight women (age 40.3+/-2.3 years, waist-to-hip ratio WHR 0.75+/-0.01, body mass index BMI 29.9+/-0.7 kg/m2), compared to 18 women with a similar degree of upper-body obesity (age 40.4+/-3years, WHR 0.91+/-0.02, BMI 29.4+/-0.7 kg/m2) and 28 control women matched for age and height. Insulin sensitivity and basal insulin effect were higher in lower-body obesity (11.2+/-0.2 min-1/[microU/ml]x 10(-4) and 0.8+/-0.2 min(-1) x 10(-2), respectively) compared to upper-body obesity (2.6+/-0.4, p < 0.001 and 0.3+/-0.05, p < 0.01) and controls (6.1+/-0.7, p < 0.02 and 0.5+/-0.07, p < 0.02). It is suggested that lower-body obesity could be associated with a reduced free fatty acids-induced inhibition of insulin action by the Randle mechanism. This study confirms that body fat distribution is a more relevant determinant than obesity itself in the pathogenesis of insulin resistance. Contrary to upper-body obesity, moderate lower-body overweight seems to be associated with high values on insulin sensitivity.
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PMID:Insulin sensitivity measured with the minimal model is higher in moderately overweight women with predominantly lower body fat. 1045 Aug 32

The aim of this work was to determine lipoprotein metabolism alterations in macrosomic newborns and to see whether these lipoprotein abnormalities are parallel or not to those found in their obese or nonobese mothers. Serum lipids, apo A-I, apo B100, lipoproteins (VLDL, LDL, HDL2, and HDL3), and LCAT activity were investigated in obese and nonobese mothers and cord blood of their macrosomic or appropriate-for-gestational-age (AGA) newborns. Serum and VLDL triglyceride concentrations were higher in obese mothers of AGA newborns than in nonobese mothers. Serum triglyceride, VLDL, and apo B100 levels were higher, while serum apo A-I and HDL2 cholesterol concentrations were lower in obese mothers of macrosomic newborns than in the other groups. In their macrosomic newborns, serum lipid, lipoprotein, apo B100, and apo A-I levels were higher as compared with those of other newborns. Macrosomic newborns of nonobese mothers had lipoprotein profiles similar to those in AGA newborns. LCAT activity was similar in both mother groups and in both newborn groups. In conclusion, maternal obesity and fetal macrosomia were associated with lipoprotein abnormalities consistent with high atherogenic risk.
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PMID:Impaired serum lipids and lipoproteins in fetal macrosomia related to maternal obesity. 1065 26

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.
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PMID:Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. 1176 56

Hepatic lipase (HL) plays a central role in LDL and HDL remodeling. High HL activity is associated with small, dense LDL particles and with reduced HDL2 cholesterol levels. HL activity is determined by an HL gene promoter polymorphism, by gender (lower in premenopausal women), and by visceral obesity with insulin resistance. The activity is affected by dietary fat intake and selected medications. There is evidence for an interaction of the HL promoter polymorphism with visceral obesity, dietary fat intake, and with lipid-lowering medications in determining the level of HL activity. The dyslipidemia with high HL activity is a potentially proatherogenic lipoprotein profile in the metabolic syndrome, in Type 2 diabetes, and in familial combined hyperlipidemia.
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PMID:Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. 1263 74

Insulin resistance and type 2 diabetes mellitus are generally accompanied by low HDL cholesterol and high plasma triglycerides, which are major cardiovascular risk factors. This review describes abnormalities in HDL metabolism and reverse cholesterol transport, i.e. the transport of cholesterol from peripheral cells back to the liver for metabolism and biliary excretion, in insulin resistance and type 2 diabetes mellitus. Several enzymes including lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT), as well as cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), participate in HDL metabolism and remodelling. Lipoprotein lipase hydrolyses lipoprotein triglycerides, thus providing lipids for HDL formation. Hepatic lipase reduces HDL particle size by hydrolysing its triglycerides and phospholipids. A decreased postheparin plasma LPL/HL ratio is a determinant of low HDL2 cholesterol in insulin resistance. The esterification of free cholesterol by LCAT increases HDL particle size. Plasma cholesterol esterification is unaltered or increased in type 2 diabetes mellitus, probably depending on the extent of triglyceride elevation. Subsequent CETP action results in transfer of cholesteryl esters from HDL towards triglyceride-rich lipoproteins, and is involved in decreasing HDL size. An increased plasma cholesteryl ester transfer is frequently observed in insulin-resistant conditions, and is considered to be a determinant of low HDL cholesterol. Phospholipid transfer protein generates small pre beta-HDL particles that are initial acceptors of cell-derived cholesterol. Its activity in plasma is elevated in insulin resistance and type 2 diabetes mellitus in association with high plasma triglycerides and obesity. In insulin resistance, the ability of plasma to promote cellular cholesterol efflux may be maintained consequent to increases in PLTP activity and pre beta-HDL. However, cellular cholesterol efflux to diabetic plasma is probably impaired. Besides, cellular abnormalities that are in part related to impaired actions of ATP binding cassette transporter 1 and scavenger receptor class B type I are likely to result in diminished cellular cholesterol efflux in the diabetic state. Whether hepatic metabolism of HDL-derived cholesterol and subsequent hepatobiliary transport is altered in insulin resistance and type 2 diabetes mellitus is unknown. Specific CETP inhibitors have been developed that exert major HDL cholesterol-raising effects in humans and retard atherosclerosis in animals. As an increased CETP-mediated cholesteryl ester transfer represents a plausible metabolic intermediate between high triglycerides and low HDL cholesterol, studies are warranted to evaluate the effects of these agents in insulin resistance- and diabetes-associated dyslipidaemia.
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PMID:Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins. 1463 88

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in low-density lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL2, and apolipoprotein A-I levels in women compared with men with high-carbohydrate or high-fat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.
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PMID:Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. 1625 6

Reduced levels of high-density lipoproteins (HDL) in non-obese and obese states are associated with increased risk for the development of coronary artery disease. Therefore, it is imperative to determine the mechanisms responsible for reduced HDL in obese states and, conversely, to examine therapies aimed at increasing HDL levels in these individuals. This paper examines the multiple causes for reduced HDL in obese states and the effect of exercise and diet--two non-pharmacologic therapies--on HDL metabolism in humans. In general, the concentration of HDL-cholesterol is adversely altered in obesity, with HDL-cholesterol levels associated with both the degree and distribution of obesity. More specifically, intra-abdominal visceral fat deposition is an important negative correlate of HDL-cholesterol. The specific subfractions of HDL that are altered in obese states include the HDL2, apolipoprotein A-I, and pre-beta1 subfractions. Decreased HDL levels in obesity have been attributed to both an enhancement in the uptake of HDL2 by adipocytes and an increase in the catabolism of apolipoprotein A-I on HDL particles. In addition, there is a decrease in the conversion of the pre-beta1 subfraction, the initial acceptor of cholesterol from peripheral cells, to pre-beta2 particles. Conversely, as a means of reversing the decrease in HDL levels in obesity, sustained weight loss is an effective method. More specifically, weight loss achieved through exercise is more effective at raising HDL levels than dieting. Exercise mediates positive effects on HDL levels at least partly through changes in enzymes of HDL metabolism. Increased lipid transfer to HDL by lipoprotein lipase and reduced HDL clearance by hepatic triglyceride lipase as a result of endurance training are two important mechanisms for increases in HDL observed from exercise.
Obesity (Silver Spring) 2007 Dec
PMID:Effect of obesity on high-density lipoprotein metabolism. 1819 93


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