Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue.
Pctp(-/-) mice that lack phosphatidylcholine transfer protein (Pctp) exhibit a marked shift toward utilization of fatty acids for oxidative phosphorylation, suggesting that Pctp may regulate the entry of fatty acyl-CoAs into mitochondria. Here, we examined the influence of Pctp expression on the function and structure of brown adipose tissue (BAT), a mitochondrial-rich, oxidative tissue that mediates nonshivering thermogenesis. Consistent with increased thermogenesis, Pctp(-/-) mice exhibited higher core body temperatures than wild-type controls at room temperature. During a 24 h cold challenge, Pctp(-/-) mice defended core body temperature efficiently enough that acute, full activation of BAT thermogenic genes did not occur. Brown adipocytes lacking Pctp harbored enlarged and elongated mitochondria. Consistent with increased fatty acid utilization, brown adipocytes cultured from Pctp(-/-) mice exhibited higher oxygen consumption rates in response to norepinephrine. The absence of Pctp expression during brown adipogenesis in vitro altered the expression of key transcription factors, which could be corrected by adenovirus-mediated overexpression of Pctp early but not late during the differentiation. Collectively, these findings support a key role for Pctp in limiting mitochondrial oxidation of fatty acids and thus regulating adaptive thermogenesis in BAT.
Kang
Hye Won
HW
Department of Medicine, Division of Gastroenterology, Harvard Medical School, Boston, MA, USA.
Ribich
Scott
S
Kim
Brian W
BW
Hagen
Susan J
SJ
Bianco
Antonio C
AC
Cohen
David E
DE
D000222:Adaptation, Physiological; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022722:Thermogenesis; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism
D049294:Phospholipid Transfer Proteins; C544602:Acot13 protein, mouse; D013869:Thiolester Hydrolases; D009638:Norepinephrine