Adiponectin Reduces Plasma Triglyceride by Increasing VLDL Triglyceride Catabolism

OBJECTIVE—Adiponectin is an adipocyte-derived hormone that plays an important role in glucose and lipid metabolism. The main aims of this study are to investigate the effects of adiponectin on VLDL triglyceride (VLDL-TG) metabolism and the underlying mechanism

Fatty acids liberated from high-density lipoprotein phospholipids by endothelial-derived lipase are incorporated into lipids in HepG2 cells.

We previously reported that endothelial-derived lipase (EDL) efficiently hydrolyses high-density-lipoprotein-derived phosphatidycholine (HDL-PC). In the present study, we assessed the ability of EDL to supply HepG2 cells with non-esterified fatty acids (NEFA) liberated from HDL-phospholipids. For this purpose, HepG2 cells infected with adenovirus encoding human EDL (EDL-Ad), or with control beta-galactosidase-expressing adenovirus (LacZ-Ad), were incubated with (14)C-HDL-PC. The analysis of the cellular lipids by TLC revealed that EDL overexpression led to an increase in the amount of cellular (14)C-lipids, whereby the label was mainly incorporated into phospholipids and triacylglycerols (TAG). Cells expressing mutant enzymically inactive EDL (MUT-EDL-Ad) contained similar amounts of (14)C-TAG but higher amounts of (14)C-phosphatidylcholine (PC) compared with LacZ-Ad-infected cells. The co-expression of CD36 augmented the EDL-mediated accumulation of (14)C-lipids in HEK-293 cells. The quadrupole MS analysis of the cellular lipids revealed an increased content of PC and TAG in EDL-expressing HepG2 cells compared with MUT-EDL-Ad-expressing and control cells. However, the MUT-EDL-Ad-expressing cells contained more PC than control cells. Additionally, EDL overexpression led to a 2-fold decrease in the amount of fatty acid synthase mRNA and, in turn, a slightly, but significantly, decreased rate of fatty acid (FA) synthesis in HepG2 cells. In the present study, we show for the first time that EDL efficiently supplies HepG2 cells with NEFA derived from HDL-PL, thus affecting cellular lipid composition and FA synthesis

Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased α-tocopherol levels in skeletal muscle

Lipoprotein lipase (LPL) has been implicated in the delivery of chylomicron-located α-tocopherol (α-TocH) to peripheral tissues. To investigate the role of LPL in the cellular uptake of α-TocH in peripheral tissue in vivo, three lines of transgenic mice [mouse creatine kinase- (MCK) L, MCK-M and MCK-H] expressing various amounts of human LPL were compared with regard to α-TocH levels in plasma, skeletal muscle, cardiac muscle, adipose tissue and brain. Depending on the copy number of the transgene, LPL activity was increased 3- to 27-fold in skeletal muscle and 1.3- to 3.7-fold in cardiac muscle. The intracellular levels of α-TocH in skeletal muscle were significantly increased in MCK-M and MCK-H animals and correlated highly with the tissue-specific LPL activity (r = 0.998). The highest levels were observed in MCK-H (21.4 nmol/g) followed by MCK-M (13.3 nmol/g) and MCK-L (8.2 nmol/g) animals when compared with control mice (7.3 nmol/g). Excellent correlation was also observed between intracellular α-TocH and non-esterified fatty acid (NEFA) levels (r = 0.998). Although LPL activities in cardiac muscle were also increased in the transgenic mouse lines, α-TocH concentrations in the heart remained unchanged. Similarly, α-TocH levels in plasma, adipose tissue and brain were unaffected by the tissue specific overexpression of LPL in muscle. The transgenic model presented in this report provides evidence that the uptake of α-TocH in muscle is directly dependent on the level of LPL expression in vivo. Increased intracellular α-TocH concentrations with increased triglyceride lipolysis and NEFA uptake might protect the myocyte from oxidative damage during increased β-oxidation.</jats:p