Journal
FASEB JOURNAL
Volume 29, Issue 1, Pages 286-299Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14-263038
Keywords
lineage tracing; adipogenesis; innervation; tyrosine hydroxylase; Myf5
Categories
Funding
- NATIONAL CANCER INSTITUTE [P30CA022453] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK020572, R01DK062292, R01DK076629] Funding Source: NIH RePORTER
- NCI NIH HHS [P30CA022453, P30 CA022453] Funding Source: Medline
- NIDDK NIH HHS [R01 DK076629, R01DK62292, R01 DK062292, P30 DK020572, R01DK76629] Funding Source: Medline
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This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, a polypeptide (PDGFR alpha) by 3-to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. Although cold stress did not increase proliferation in inguinal white adipose tissue (ingWAT), the percentage of BAs, defined as multilocular adipocytes that express uncoupling protein 1, rose from undetectable to 30% of total adipocytes. To trace the origins of cold-induced BAs, we genetically tagged PDGFR(alpha+) cells and adipocytes prior to cold exposure, using Pdgfra-Cre recombinase estrogen receptor T2 fusion protein (CreER(T2)) and adiponectin-CreER(T2), respectively. In iBAT, cold stress triggered the proliferation and differentiation of PDGFR(alpha+) cells into BAs. In contrast, all newly observed BAs in ingWAT (5207 out of 5207) were derived from unilocular adipocytes tagged by adiponectin-CreER(T2)-mediated recombination. Surgical denervation of iBAT reduced cold-induced brown adipogenesis by > 85%, whereas infusion of norepinephrine (NE) mimicked the effects of cold in warm-adapted mice. NE-induced de novo brown adipogenesis in iBAT was eliminated in mice lacking beta 1-adrenergic receptors. These observations identify a novel tissue niche for brown adipogenesis in iBAT and further define depotspecific mechanisms of BA recruitment.
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