High-Density Lipoprotein Cholesterol Concentrations and Postheparin Hepatic and Lipoprotein Lipases in Obesity: Relationships with Plasma Insulin Levels

Cominacini, Luciano; Garbin, Ulisse; Davoli, A.; Campagnola, M.; Santis, Adriano De; Pasini, C; Pastorino, Alessandra; Bosello, O

doi:10.1159/000177766

Cited by 24 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings may help to explain observations made in several previous studies. These previous studies have demonstrated correlations either between elevated plasma hepatic lipase activity (11)(12)(13)17) or hypoadiponectinemia (8 -10,18) with parameters of the insulin resistance (metabolic) syndrome, such as obesity, type 2 diabetes, hypertriglyceridemia, and low HDL cholesterol. Hepatic lipase is regulated predominantly by cell cholesterol content, steroids, and thyroid hormones (3).…”

Section: Statistical Analysesmentioning

confidence: 99%

“…The hepatic lipase regulatory interactions with insulin are, however, not clear-cut, and hepatic lipase responsiveness to insulin is controversial. Most studies in patients with chronic hy- perinsulinemia show higher hepatic lipase activities than in control subjects (11,13,17,19), whereas others report either reduced hepatic lipase activity in type 1 diabetic patients (20) or upregulated hepatic lipase activity by insulin treatment in general (21,22). Therefore, hepatic lipase activity appears to be not clearly upregulated by insulin, and the precise mechanism that links hepatic lipase activity to insulin resistance remains unclear.…”

Section: Statistical Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Low Plasma Adiponectin Levels Are Associated With Increased Hepatic Lipase Activity In Vivo

et al. 2005

View full text Add to dashboard Cite

OBJECTIVE -Hepatic lipase plays a key role in hydrolyzing triglycerides and phospholipids present in circulating plasma lipoproteins. Plasma hepatic lipase activity is known to be regulated by several hormonal and metabolic factors, but hepatic lipase responsiveness to insulin is still controversial. Hypoadiponectinemia is known to be associated with insulin resistance, diabetes, and obesity. These conditions are often characterized by high plasma triglyceride and low HDL cholesterol levels, and they have been shown to be associated with high plasma hepatic lipase activity. We therefore raised the question whether adiponectin may be associated with plasma hepatic lipase activity in vivo.RESEARCH DESIGN AND METHODS -We measured plasma adiponectin and postheparin hepatic lipase activity in 206 nondiabetic men and in a second group of 110 patients with type 2 diabetes. The correlation of these parameters with markers of insulin resistance and systemic inflammation was investigated.RESULTS -In nondiabetic patients, adiponectin levels were significantly inversely correlated with plasma hepatic lipase activity (r ϭ Ϫ0.4, P Ͻ 0.01). These results were confirmed in the group of patients with type 2 diabetes (r ϭ Ϫ0.32, P ϭ 0.004). Multivariate analysis revealed that adiponectin was the strongest factor influencing hepatic lipase activity. The association was independent of age, sex, BMI, plasma triglycerides, insulin, HDL cholesterol, and highsensitivity C-reactive protein and accounted for ϳ10 and 12% of the variation in hepatic lipase activity in the two different patient cohorts, respectively.CONCLUSIONS -These results demonstrate for the first time a significant inverse association between adiponectin and postheparin plasma hepatic lipase activity that is independent of other factors such as markers of insulin resistance or inflammation. Therefore, adiponectin, rather than insulin, may represent an important factor contributing to the regulation of hepatic lipase activity in both nondiabetic individuals and patients with type 2 diabetes. The effect of adiponectin on hepatic lipase activity may also help to explain the HDL cholesterol-elevating action of adiponectin. Diabetes Care 28:2181-2186, 2005H epatic lipase functions as a lipolytic enzyme that hydrolyzes triglycerides and phospholipids in lipoproteins of intermediate and high density. It is thereby involved in the formation of small, dense LDL and represents a major determinant of the plasma HDL cholesterol concentration (1,2). Hepatic lipase activity is regulated by several hormonal and metabolic factors (3). In insulin resistance, most studies show increased hepatic lipase activity, although the exact regulation of hepatic lipase in insulin resistance is still controversial (4). Adiponectin is a member of a class of bioactive substances known as adipocytokines (5). It is related to tumor necrosis factor-␣ expression (6) and has the ability to suppress tumor necrosis factor-␣-induced activation of nuclear transcription factor B (7), thereby demonstrating anti...

show abstract

Section: Statistical Analysesmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Low Plasma Adiponectin Levels Are Associated With Increased Hepatic Lipase Activity In Vivo

et al. 2005

View full text Add to dashboard Cite

show abstract

“…33 Elevated insulin concentrations may also influence the activity of hepatic lipase, and insulin resistance may affect lipoprotein lipase, both of which are involved in the metabolism of HDL cholesterol. 34,35 Reduced lipoprotein lipase and increased hepatic lipase activity result in decreased maturation and increased catabolism of HDL cholesterol, respectively. Rocchini 36 has studied the relationship of insulin sensitivity to blood pressure in obese adolescents and found that increased circulating levels of insulin are related to blood pressure elevation.…”

Section: Discussionmentioning

confidence: 99%

Association of Body Fat Distribution and Cardiovascular Risk Factors in Children and Adolescents † 512

et al. 1998

View full text Add to dashboard Cite

Background-Obesity is associated with increased risk of cardiovascular disease in adults and less favorable cardiovascular risk factor status in children and adolescents. In adults, fat distribution has been shown to be related to lipid and lipoprotein concentrations, blood pressure levels, and left ventricular mass. These relationships have not been extensively studied in young subjects. Methods and Results-This was a cross-sectional study of 127 children and adolescents 9 to 17 years of age. Dual-energy x-ray absorptiometry was used to measure total and regional fat mass. The dependent variables were fasting lipid and lipoprotein concentrations, systolic and diastolic blood pressures, and left ventricular mass. There were significant (PϽ0.05) univariate correlations between fat distribution and log triglycerides (rϭ0.27), log HDL cholesterol (rϭϪ0.23), systolic blood pressure (rϭ0.26), and left ventricular mass (rϭ0.37). Multiple regression analysis showed that the significant independent correlates for triglycerides and HDL cholesterol were age and fat distribution; for systolic blood pressure, height and fat distribution; and for left ventricular mass, height, race, sex, and fat distribution. Conclusions-These results demonstrate that fat distribution is a more important independent correlate of cardiovascular risk factors than percent body fat in children and adolescents.

show abstract

“…Men have a higher HL activity than women because of a number of endogenous factors, such as central adiposity and sex steroid hormones (14,15,26,39,40). Recently, Carr et al (41) also demonstrated that intra-abdominal fat is a major component of the sex difference in HL activity.…”

Section: Hl Activity In Type 2 Diabetesmentioning

confidence: 99%

Atorvastatin Dose-Dependently Decreases Hepatic Lipase Activity in Type 2 Diabetes

Berk-Planken

Hoogerbrugge²,

Stolk

et al. 2003

Diabetes Care

View full text Add to dashboard Cite

OBJECTIVE -Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the hepatic lipase gene, the LIPC promoter variant in type 2 diabetes. Therefore, we studied the effect of atorvastatin 10 mg (A10) and 80 mg (A80) on HL activity in 198 patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -Patients (aged 45-75 years, without manifest coronary artery disease, total cholesterol 4.0 -8.0 mmol/l, and fasting triglycerides [TG] 1.5-6.0 mmol/l) were included in a double-blind, randomized, placebo-controlled trial for 30 weeks (Diabetes Atorvastatin Lipid Intervention study).RESULTS -HL activity at baseline was significantly higher in our population compared with an age-matched control group without type 2 diabetes (406 Ϯ 150 vs. 357 Ϯ 118 units/l). HL activity in men versus women (443 Ϯ 158 vs. 358 Ϯ 127 units/l), in carriers of the LIPC C/C allele versus carriers of the T/T allele (444 Ϯ 142 vs. 227 Ϯ 96 units/l), and in Caucasians versus blacks (415 Ϯ 150 vs. 260 Ϯ 127 units/l) all differed significantly (P Ͻ 0.001). Atorvastatin dose-dependently decreased HL (A10, Ϫ11%; A80, Ϫ22%; both P Ͻ 0.001). Neither sex nor the LIPC C3 T variation influenced the effect of atorvastatin on HL activity.CONCLUSIONS -Sex, LIPC promoter variant, and ethnicity significantly contribute to the baseline variance in HL activity. Atorvastatin treatment in diabetic dyslipidemia results in a significant dose-dependent decrease in HL activity, regardless of sex or the LIPC promoter variant. Diabetes Care 26:427-432, 2003H epatic lipase (HL) is involved in the metabolism of several lipoproteins (1) and is a key player in HDL metabolism (2,3). Hydrolysis of phospholipids and triglycerides by HL leads to the conversion of large, buoyant HDL2 to small, dense HDL3 and may induce cholesterol (ester) flux to the liver (4,5). In this way, HL is involved in reverse cholesterol transport and is a major determinant of plasma HDL concentration (6,7). HL also plays a role in the formation of small, dense LDL and contributes to the expression of the LDL subclass phenotype (8,9). Finally, HL is proposed to be involved in postprandial lipid clearing (10). Obviously, HL activity seems to be central in the metabolism of lipoproteins strongly associated with coronary artery disease (CAD) risk in type 2 diabetes. Zambon et al. (11) identified HL as a focal point for the development and treatment of CAD. Genetic variation, sex, and abdominal fat mass affect HL activity in humans (12-15).In the human hepatic lipase gene (LIPC), variants are found that affect lipase activity (16 -18). Besides rather rare variants leading to complete HL deficiency (19,20), common base substitutions in the proximal LIPC promoter affect HL activity up to twofold (15,21,22). Four base substitutions, Ϫ250 G3 A, Ϫ514 C3 T, Ϫ710 T3 C, and Ϫ763 A3 G, were found to be completely linked (2...

show abstract

High-Density Lipoprotein Cholesterol Concentrations and Postheparin Hepatic and Lipoprotein Lipases in Obesity: Relationships with Plasma Insulin Levels

Cited by 24 publications

References 22 publications

Low Plasma Adiponectin Levels Are Associated With Increased Hepatic Lipase Activity In Vivo

Low Plasma Adiponectin Levels Are Associated With Increased Hepatic Lipase Activity In Vivo

Association of Body Fat Distribution and Cardiovascular Risk Factors in Children and Adolescents † 512

Atorvastatin Dose-Dependently Decreases Hepatic Lipase Activity in Type 2 Diabetes

Contact Info

Product

Resources

About