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Publication : Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis.

First Author  Huang ZH Year  2011
Journal  J Lipid Res Volume  52
Issue  9 Pages  1733-41
PubMed ID  21743035 Mgi Jnum  J:175549
Mgi Id  MGI:5286011 Doi  10.1194/jlr.M017160
Citation  Huang ZH, et al. (2011) Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis. J Lipid Res 52(9):1733-41
abstractText  Expression of apoE in adipocytes has been shown to have an important role in modulating adipocyte triglyceride (TG) metabolism and gene expression that is independent of circulating and extracellular apoE. The impact of adipocyte expression of common human apoE isoforms was evaluated using adipocytes harvested from human apoE2, -3, and -4 knock-in mice. Expression of the apoE2 isoform was associated with an increase in adipocyte apoE gene expression and apoE synthesis. Newly synthesized apoE2 was unstable in adipocytes and demonstrated increased degradation and decreased secretion. ApoE2-expressing mice were hyperlipidemic, and had increased size of gonadal fat pads and of adipocytes, compared with apoE3 mice. In isolated cells, however, expression of the apoE2 isoform produced defective lipogenesis and increased TG hydrolysis. Incubation of adipose tissue with apoE3-containing TG-rich lipoproteins resulted in a significant increase in TG in adipose tissue from apoE3 and -E4 mice, but not apoE2 mice. Reduced capacity to internalize FFA as lipogenic substrate contributed to defective lipogenesis. Newly synthesized apoE2 is unstable in adipocytes and results in decreased adipocyte TG synthesis and defective FA uptake. These changes recapitulate those observed in apoE knockout adipocytes and have implications for understanding metabolic disturbances in humans expressing the E2 isoform.
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