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miR‐196b‐5p controls adipocyte differentiation and lipogenesis through regulating mTORC1 and TGF‐β signaling
Author(s) -
Shi Yaru,
Li Fang,
Wang Shan,
Wang Changlan,
Xie Yan,
Zhou Jie,
Li Xiaoxia,
Wang Baoli
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901562rr
Subject(s) - adipogenesis , mtorc1 , lipogenesis , biology , microbiology and biotechnology , progenitor cell , cancer research , signal transduction , stem cell , endocrinology , pi3k/akt/mtor pathway , mesenchymal stem cell , adipose tissue
Abstract MicroRNAs have been reported to play a role in adipogenesis and obesity. This study was performed to investigate the role of miR‐196b‐5p in adipogenesis and the mechanism involved. The data revealed that miR‐196b‐5p expression increased in primary or established marrow stromal progenitor cells after adipogenic treatment. Supplementing miR‐196b‐5p in the progenitor cells stimulated adipogenic differentiation and lipogenesis, along with the induction of adipogenic and lipogenic factors. Conversely, inhibition of endogenous miR‐196b‐5p blocked adipogenesis and lipogenesis. Tuberous sclerosis 1 (Tsc1) and transforming growth factor‐β receptor 1 (TGFBR1) were demonstrated to be the direct target genes of miR‐196b‐5p. Supplementing miR‐196b‐5p activity in progenitor cells reduced the protein level of TSC1 and activated mammalian target of rapamycin complex 1 (mTORC1) signaling. We further demonstrated that the perturbation of TSC1 in progenitor cells altered the trend of adipogenic differentiation and lipogenesis. Overexpression of Tsc1 or inactivation of mTORC1 signaling attenuated the stimulation of adipogenic differentiation and lipogenesis by miR‐196b‐5p. Overexpression of Tgfbr1 also partially blocked the adipogenic effect of miR‐196b‐5p. Further investigations demonstrated that zinc finger E‐box‐binding homeobox 1 (ZEB1) transcriptionally upregulated miR‐196b‐5p expression. The current study suggests that miR‐196b‐5p promotes adipogenic differentiation and lipogenesis in progenitor cells through targeting TSC1 and TGFBR1 and therefore regulating mTORC1 and TGF‐β signaling.