title: Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16.
abstract: Visceral adiposity is strongly associated with metabolic disease risk, whereas subcutaneous adiposity is comparatively benign. However, their relative physiological importance in energy homeostasis remains unclear. Here, we show that after 24-h fasting, the subcutaneous adipose tissue of mice acquires key properties of visceral fat. During this fast-induced 'visceralization', upregulation of miR-149-3p directly targets PR domain containing 16 (PRDM16), a key coregulatory protein required for the 'browning' of white fat. In cultured inguinal preadipocytes, overexpression of miR-149-3p promotes a visceral-like switch during cell differentiation. Mice deficient in miR-149-3p display an increase in whole-body energy expenditure, with enhanced thermogenesis of inguinal fat. However, a visceral-like adipose phenotype is observed in inguinal depots overexpressing miR-149-3p. These results indicate that in addition to the capacity of 'browning' to defend against hypothermia during cold exposure, the subcutaneous adipose depot is also capable of 'whitening' to preserve energy during fasting, presumably to maintain energy balance, via miR-149-3p-mediated regulation of PRDM16.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Hanying
authors.initials: H
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcia-Ruiz
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Road, Nanjing, Jiangsu 210046, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
mesh_terms: D017667:Adipocytes; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology; D052436:Adipose Tissue, White / Q000166:cytology / Q000502:physiology; D050154:Adiposity / Q000502:physiology; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting / Q000523:psychology*; D005260:Female; D055785:Gene Knockdown Techniques; D006119:Groin; D057809:HEK293 Cells; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D050151:Subcutaneous Fat / Q000166:cytology / Q000502:physiology; D022722:Thermogenesis / Q000502:physiology; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000070416:Antagomirs; D004268:DNA-Binding Proteins; C000628220:MIRN149 microRNA, mouse; D035683:MicroRNAs; C521133:Prdm16 protein, mouse; D014157:Transcription Factors