Decreased Plasma Lipoprotein Lipase in Hypoadiponectinemia

Abstract

OBJECTIVE -Adiponectin is a plasma protein expressed in adipose tissue. Hypoadiponectinemia is associated with low HDL cholesterol and high plasma triglycerides, which also characterize lipoprotein lipase (LPL) deficiency syndromes. Recently, dramatically increased LPL activity was reported in mice overexpressing adiponectin. We therefore speculated that adiponectin may directly affect LPL in humans. RESULTS -Nondiabetic subjects with decreased plasma adiponectin had lower LPL activity (r ϭ 0.42, P Ͻ 0.0001). This association of plasma adiponectin with LPL activity was confirmed in the second group of patients with type 2 diabetes (r ϭ 0.37, P Ͻ 0.0001). Multivariate analysis revealed that adiponectin was the strongest factor influencing LPL activity, accounting for 23% of the variation in LPL activity in nondiabetic subjects and for 26% of the variation in LPL activity in type 2 diabetic patients. These associations were independent of plasma CRP and HOMA-IR. RESEARCH DESIGN AND METHODSCONCLUSIONS -These results demonstrate an association of decreased postheparin LPL activity with low plasma adiponectin that is independent of systemic inflammation and insulin resistance. Therefore, LPL may represent a link between low adiponectin levels and dyslipidemia in both nondiabetic individuals and patients with type 2 diabetes. Diabetes Care 27:2925-2929, 2004L ipoprotein lipase (LPL) is a pivotal enzyme in lipid metabolism (1). Low LPL activity may be observed in the diabetic dyslipidemia of low HDL cholesterol and high plasma triglycerides (2). Plasma LPL activity has been shown to be decreased in insulin-resistant subjects without diabetes (3), and recently, overall plasma LPL activity was inversely associated with insulin resistance in patients with type 2 diabetes (4). LPL expression is also modulated by systemic inflammation. Tumor necrosis factor (TNF)-␣ and interleukin-6 reduce the expression of LPL at the transcriptional level and decrease LPL activity in plasma (5,6).Adiponectin, the gene product of the apM1 (adipose most abundant gene transcript 1) gene (7), is a member of bioactive substances known as adipocytokines. Adiponectin plasma levels are negatively correlated with BMI (8), insulin resistance (9), and type 2 diabetes (9). Furthermore, adiponectin is associated with lower TNF-␣ expression (10) and has been shown to suppress TNF-␣-induced activation of nuclear transcription factor-B (11), thereby demonstrating antiinflammatory potential. Recently published data suggest that low levels of adiponectin are associated with a lipid profile of low HDL cholesterol and increased plasma triglycerides (12) that is also characteristic for the hypertriglyceridemia in LPL deficiency. LPL is mainly expressed in muscle and adipose tissue (1), the unique source of adiponectin. These findings suggest a direct or indirect relationship between LPL and adiponectin by an unknown mechanism. We therefore investigated, in two different groups of patients, whether adiponectin influences LPL plasma activity and concentration an...

In treatment-naïve and antiretroviral-treated subjects with HIV, reduced plasma adiponectin is associated with a reduced fractional clearance rate of VLDL, IDL and LDL apolipoprotein B-100

“…Lipoprotein lipase mRNA has also been shown to be lower in HIV patients with lipodystrophy than in patients without lipodystrophy [13], suggesting that regulation may be at the level of transcription. In a transgenic mouse with chronically elevated adiponectin, lipoprotein lipase has been shown to be increased [14]. The prolonged residence time of apoBcontaining lipoproteins will allow exchange of triglyceride for cholesterol esters with HDL.…”

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

“…The degree of insulin resistance was estimated by homeostasis model assessment of insulin resistance index (HOMA-IR) according to the method recommended by Levy et al [9]. Post-heparin lipoprotein lipase and hepatic lipase activity were detected as previously described in detail [10][11][12]. Briefly, venous blood was drawn into EDTA tubes before and 10 min after intravenous injection of 60 IU of heparin (Braun Melsungen, Melsungen, Germany) per kg body weight, after which lipoprotein lipase and hepatic lipase activities were determined with a triolein/phosphatidylcholine emulsion.…”

Adiponectin Inversely Correlates with High Sensitive C-reactive Protein and Triglycerides, but not with Insulin Sensitivity, in Apparently Healthy Japanese Men

“…The peptide lowers serum triglycerides most likely through catabolism of apolipoprotein(s) [15][16][17], suppresses subclinical inflammation [9], and improves insulin sensitivity [28], all of which are linked to antiatherogenesis [28]. In a population with increased insulin resistance, adiponectin's insulin-sensitizing action may be important for its antiatherogenetic effect.…”

“…Insulin sensitizing action of adiponectin has been considered important for its anti-atherogenic property based on the clinical data obtained in insulin-resistant subjects [8,10,15,16]. Whereas, role of adiponectin in lipid metabolism and inflammation independently from its insulinsensitizing action [9,[16][17][18] has recently been reported. Apparently healthy Japanese are in general not obese and not insulin-resistant, nevertheless, hypoadiponectinemia is a risk factor for coronary heart disease in this population [14] as in other insulin-resistant populations [15].…”