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Papers In Press, published online ahead of print November 1, 2009
J. Lipid Res., doi:10.1194/jlr.M900013-JLR200

This Article Full Text Full Text (PDF) Supplemental Data Supplemental Data All Versions of this Article: M900013-JLR200v1 50/11/2212    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Won Kang, H. Articles by Cohen, D. E. PubMed PubMed Citation Articles by Won Kang, H. Articles by Cohen, D. E. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 2212-2221, November 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue^[S]

Hye Won Kang^*, Scott Ribich^1,, Brian W. Kim^2,, Susan J. Hagen, Antonio C. Bianco^2, and David E. Cohen^3,*,**

^* Department of Medicine, Division of Gastroenterology, Harvard Medical School, Boston, MA
Division of Endocrinology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
^** Division of Health and Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston, MA

³ To whom correspondence should be addressed. e-mail: dcohen{at}partners.org

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.

Supplementary key words lipid binding protein • fatty acyl-CoA • fatty acid • brown adipocyte • thioesterase • phosphatidylcholine transfer protein

Abbreviations: BAT, brown adipose tissue; GFP, green fluorescent protein; Nrf, nuclear respiratory factor; OCR, oxygen consumption rate; Pctp, phosphatidylcholine transfer protein; Pgc, peroxisome proliferator activate receptor coactivator; Ppar, peroxisome proliferator activate receptor; PK, protein kinase; Rpl32, L32 ribosomal protein; Tfam, mitochondrial transcription factor A; Them, thioesterase superfamily member; Ucp, uncoupling protein

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