Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue.

Abstract:

:Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, the protein hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation. Levels of HILPDA markedly increased during 3T3-L1 adipocyte differentiation. Nevertheless, silencing of Hilpda using small interfering RNA or overexpression of Hilpda using adenovirus did not show a clear impact on 3T3-L1 adipogenesis. Following β-adrenergic stimulation, the silencing of Hilpda in adipocytes did not significantly alter the release of nonesterified fatty acids (NEFA) and glycerol. By contrast, adenoviral-mediated overexpression of Hilpda modestly attenuated the release of NEFA from adipocytes following β-adrenergic stimulation. In mice, adipocyte-specific inactivation of Hilpda had no effect on plasma levels of NEFA and glycerol after fasting, cold exposure, or pharmacological β-adrenergic stimulation. In addition, other relevant metabolic parameters were unchanged by adipocyte-specific inactivation of Hilpda. Taken together, we find that HILPDA is highly abundant in adipose tissue, where its levels are induced by peroxisome proliferator-activated receptor γ and β-adrenergic stimulation. In contrast to the reported inhibition of lipolysis by HILPDA in hepatocytes, our data do not support an important direct role of HILPDA in the regulation of lipolysis in adipocytes in vivo and in vitro.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Dijk W,Mattijssen F,de la Rosa Rodriguez M,Loza Valdes A,Loft A,Mandrup S,Kalkhoven E,Qi L,Borst JW,Kersten S

doi

10.1210/en.2016-1809

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

1231-1251

issue

5

eissn

0013-7227

issn

1945-7170

pii

3074048

journal_volume

158

pub_type

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