Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: potential interaction with obesity

Zhang, Cuilin; López‐Ridaura, Ruy; Rimm, Eric B.; Li, T.; Hunter, David J.; Hu, Frank B.

doi:10.1007/s00125-006-0235-2

Cited by 21 publications

(19 citation statements)

References 47 publications

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“…Others have suggested that decreasing HL, another characteristic of the -514T allele should benefit the lipid profile of obese subjects or those with high plasma triglycerides (6, 29, 30). The results from our study contrast those from a previous report among diabetics, showing that the -514T allele was associated with increased risk of MI among obese individuals (31). The reasons for this discrepancy are uncertain, although it suggests that results within diabetic populations can not be generalized to non-diabetic populations.…”

Section: Discussioncontrasting

confidence: 99%

Association between hepatic lipase −514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference

Baylin

Ruiz-Narváez

Jensen

et al. 2010

Nutrition, Metabolism and Cardiovascular Diseases

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Section: Discussioncontrasting

confidence: 99%

Association between hepatic lipase −514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference

Baylin

Ruiz-Narváez

Jensen

et al. 2010

Nutrition, Metabolism and Cardiovascular Diseases

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“…Third, HL activity increases with menopause, is associated with increased waist circumference and onset of premature CAD [37] (footnote 4). Finally, sedentary lifestyle is associated with elevated HL activity, central obesity and premature CAD [38,39,40,41,42,43,44,45]. …”

Section: Clinical Studiesmentioning

confidence: 99%

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

Brunzell

Zambón

Deeb

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Increased or decreased hepatic lipase (HL) activity has been associated with coronary artery disease (CAD). This is consistent with the findings that gene variants that influence HL activity were associated with increased CAD risk in some population studies but not in others. In this review, we will explain the conditions that influence the effects of HL on CAD. Increased HL is associated with smaller and denser LDL (sdLDL) and HDL (HDL3) particles, while decreased HL is associated with larger and more buoyant LDL and HDL particles. The effect of HL activity on CAD risk is dependent on the underlying lipoprotein phenotype or disorder. Central obesity with hypertriglyceridemia (HTG) is associated with high HL activity that leads to the formation of sdLDL that is proatherogenic. In the absence of HTG, where large buoyant cholesteryl ester-enriched LDL is prominent, elevation of HL does not raise the risk for CAD. In HTG patients, drug therapy that decreases HL activity selectively decreases sdLDL particles, an antiatherogenic effect. Drug therapy that raises HDL2 cholesterol has not decreased the risk for CAD. In trials where inhibition of cholesterol ester transfer protein (CETP) or HL occurs, the increase in HDL2 most likely is due to inhibition of catabolism of HDL2 and impairment of reverse cholesterol transport (RCT). In patients with isolated hypercholesterolemia, but with normal triglyceride levels and big-buoyant LDL particles, an increase in HL activity is beneficial; possibly because it increases RCT. Drugs that lower HL activity might decrease the risk for CAD only in hypertriglyceridemic patients with sdLDL by selectively clearing sdLDL particles from plasma, which would override the potentially pro-atherogenic effect on RCT.

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“…Other studies have shown that HL gene is associated with dyslipidemia characterised by high levels of atherogenic LDL, low HDL and high triglycerides (Teslovich et al 2010). The role of HL in cardiovascular disease progression in humans is controversial and HL increased levels are beneficial in patients with hypercholesterolemia (Dugi et al 2001) but detrimental in subjects with central obesity and IR (Teran-Garcia et al 2005, Zhang et al 2006, Brunzell et al 2011. Therefore, the effect of HL in disease progression is highly dependent on the underlying lipoprotein and lipid phenotype (Brunzell et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis

Andrés‐Blasco¹,

Herrero-Cervera²,

Vinué³

et al. 2015

Journal of Endocrinology

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Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to global health, and their incidence is increasing at an alarming rate. Non-alcoholic fatty liver disease, which affects up to 90% of obese people and nearly 70% of the overweight, is commonly associated with MetS characteristics such as obesity, insulin resistance, hypertension and dyslipidemia. In the present study, we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat, high-cholesterol diet produced dyslipidemia including hypercholesterolemia, hypertriglyceridemia and increased non-esterified fatty acid levels. These changes were accompanied by glucose intolerance, pancreatic and hepatic inflammation and steatosis. In addition, compared with WT mice, HL K/K mice exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of CD4CTh17C cells. Consistent with increased inflammation, livers from HL K/K mice had augmented activation of the stress SAPK/JNK-and p38-pathways compared with the activation levels of the kinases in livers from WT mice. Analysis of HL K/K and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in HL K/K mice without any other changes in inflammation or hepatic steatosis. Altogether, these results indicate that dyslipidemia induced by HL-deficiency in combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and inflammation in mice which are, at least in part, mediated by the activation of the stress SAPK/JNK-and p38-pathways. Future studies are warranted to asses the viability of therapeutic strategies based on the modulation of these kinases to reduce hepatic steatosis associated to lipase dysfunction.

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Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: potential interaction with obesity

Cited by 21 publications

References 47 publications

Association between hepatic lipase −514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference

Association between hepatic lipase −514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis

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