Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C.

Abstract

Recent data suggest that plasma leptin may represent a cardiovascular risk factor in diabetic patients. To gain further insight into the role of leptin in atherogenesis associated with diabetes, we investigated in the present study the role of this hormone in the regulation of macrophage lipoprotein lipase (LPL), a proatherogenic cytokine overexpressed in patients with type 2 diabetes. Treatment of human macrophages with leptin (1-10 nmol/l) increased LPL expression, at both the mRNA and protein levels. Pretreatment of these cells with anti-leptin receptor (Ob-R) antibody, protein kinase C (PKC) inhibitors, calphostin C, and GF109203X, or the antioxidant N-acetylcysteine (NAC) blocked the effects of leptin. Similar results were observed in leptin-treated J774 macrophages. In these cells, leptin increased the membrane expression of conventional PKC isoforms and downregulation of endogenous PKC expression abolished the effects of leptin on macrophage LPL expression. In leptin-treated J774 cells, enhanced LPL synthetic rate and increased binding of nuclear proteins to the activated protein-1 (AP-1) consensus sequence of the LPL gene promoter were also observed. This latter effect was abrogated by GF109203X. Overall, these data demonstrate that binding of leptin at the macrophage cell surface increases, through oxidative stress- and PKC-dependent pathways, LPL expression. This effect appears to be exerted at the transcriptional level and to involve AP-1 activation.

8 Figures and Tables

050100150'05'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

459 Citations

Semantic Scholar estimates that this publication has 459 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Maingrette2003LeptinIL, title={Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C.}, author={Fritz Maingrette and Genevi{\`e}ve Renier}, journal={Diabetes}, year={2003}, volume={52 8}, pages={2121-8} }