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Journal of Lipid Research, Vol. 48, 41-51, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat

Bingzhong Xue¹, Jong-Seop Rim, Jessica C. Hogan, Ann A. Coulter, Robert A. Koza and Leslie P. Kozak²

Pennington Biomedical Research Center, Baton Rouge, LA 70808

The online version of this article (available at http://www.jlr.org) contains supplemental data.

Published, JLR Papers in Press, October 14, 2006.

¹ Present address of B. Xue: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.

² To whom correspondence should be addressed. e-mail: kozaklp{at}pbrc.edu

Cold exposure induces brown adipocytes in retroperitoneal fat (RP) of adult A/J mice but not in C57BL/6J (B6) mice. In contrast, induction of the mitochondrial uncoupling protein 1 gene (Ucp1) in interscapular brown adipose tissue (iBAT) shows no strain dependence. We now show that unlike iBAT, in which Ucp1 was expressed in the fetus and continued throughout life, in RP, Ucp1 was transiently expressed between 10 and 30 days of age and then disappeared. Similar to the lack of genetic variation in the expression of Ucp1 in iBAT during cold induction of adult mice, no genetic variation in Ucp1 expression in iBAT was detected during development. In contrast, UCP1-positive multilocular adipocytes, together with corresponding increases in Ucp1 expression, appeared in RP at 10 days of age in A/J and B6 mice, but with much higher expression in A/J mice. At 20 days of age, brown adipocytes represent the major adipocyte present in RP of A/J mice. The disappearance of brown adipocytes by 30 days of age suggested that tissue remodeling occurred in RP. Genetic variability in Ucp1 expression could not be explained by variation in the expression of selective transcription factors and signaling molecules of adipogenesis. In summary, the existence of genetic variability between A/J and B6 mice during the development of brown adipocyte expression in RP, but not in iBAT, suggests that developmental mechanisms for the brown adipocyte differentiation program are different in these adipose tissues.

Supplementary key words white fat development • mitochondrial uncoupling protein 1 • transcription factors of adipogenesis • immunoblot analysis • quantitative reverse transcription polymerase chain reaction • immunohistology • peroxisome proliferator-activated receptor knockout • peroxisome proliferator-activated receptor coactivator-1 • A/J mice • C57BL/6J mice

Abbreviations: ATF, activating transcription factor; B6, C57BL/6J; COXI, cytochrome c oxidase subunit I; CREB, cAMP response element binding protein; DIO2, type 2 T4 deiodinase; iBAT, interscapular brown adipose tissue; PGC1, peroxisome proliferator-activated receptor coactivator-1; PKA, protein kinase A; PPAR, peroxisome proliferator-activated receptor; QTL, quantitative trait locus; RP, retroperitoneal fat; UCP1, uncoupling protein 1

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