Hypoxia-Inducible Lipid Droplet-Associated Is Not a Direct Physiological Regulator of Lipolysis in Adipose Tissue.
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.
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, The Netherlands.
Wieneke
W
Dijk
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, The Netherlands.
Frits
F
Mattijssen
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, The Netherlands.
Montserrat
M
de la Rosa Rodriguez
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, The Netherlands.
Angel
A
Loza Valdes
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
Anne
A
Loft
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
Susanne
S
Mandrup
Molecular Cancer Research and Center for Molecular Medicine, University Medical Centre Utrecht, 3584 CG Utrecht, The Netherlands.
Eric
E
Kalkhoven
University of Michigan Medical School, Ann Arbor, Michigan 48105.
Ling
L
Qi
Laboratory of Biochemistry, Microspectroscopy Centre, Wageningen University, 6708 WE Wageningen, The Netherlands.
Jan Willem
JW
Borst
Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen, The Netherlands.|University of Michigan Medical School, Ann Arbor, Michigan 48105.
Sander
S
Kersten
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005260:Female; D066292:Lipid Droplets / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000502:physiology*
C000601089:HIG2 protein, mouse; D009363:Neoplasm Proteins