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Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity.

ABSTRACT: The purpose of this research was to identify if Sirt3 plays a role in marrow adipogenesis and adipokines secretion, especially adiponectin using bone marrow-derived stroma (ST2) cell model. Sirt3 overexpression leads to a significant increase in adipogenesis compared to controls. The induction of adipogenesis by Sirt3 is associated with increased gene expression of adipocyte markers as well as adiponectin/adipokines. In sharp contrast, the inhibition of Sirt3 exhibited significantly decreased adipogenesis, adipocyte markers, and adiponectin/adipokines compared to the controls. Interestingly, perilipin 1 (Plin 1) expression was decreased in Sirt3 induction but increased in Sirt3 inhibition. One hundred and fifteen mitochondrial acetylated peptides from 67 mitochondrial proteins had lower levels of acetylation in adipocytes induced by Sirt3 overexpression (Sirt3OE) compared to the control. Of the 67 proteins less enriched in acetylation, 22 acetylated proteins were decreased by more than twofold. These proteins are considered potential Sirt3 substrates in adipogenesis. In conclusion, Sirt3 has a novel, important role in modulating adipogenesis and adiponectin/adipokine expression. The connection axis among Sirt3-adipogenesis-adipokines was linked to its substrates by mass spectrometry analysis. These findings contribute to the efforts of revealing Sirt3 functions and Sirt3 usage as a potential target for treatment of metabolic homeostasis and diseases including type 2 diabetes.

SUBMITTER: Ma O

PROVIDER: S-EPMC7667394 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity.

Ma Oanh O Le Truc T Talbott George G HoangThao Nguyen Tram T Ha Dorothy D Ho Linh L

Pharmacology research & perspectives 20201201 6

The purpose of this research was to identify if Sirt3 plays a role in marrow adipogenesis and adipokines secretion, especially adiponectin using bone marrow-derived stroma (ST2) cell model. Sirt3 overexpression leads to a significant increase in adipogenesis compared to controls. The induction of adipogenesis by Sirt3 is associated with increased gene expression of adipocyte markers as well as adiponectin/adipokines. In sharp contrast, the inhibition of Sirt3 exhibited significantly decreased ad ...[more]

PMID: 33191653

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Project description:Background/aims: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type‐2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO) opening the possibility that FGF21 is a cross‐talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion. Methods/study design: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole‐body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro. Results: Serum FGF21 concentrations were more than two‐fold higher in MUHO as compared to 37 MHO subjects (457 ±378 vs. 211 ±123 pg/mL; p<0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p<0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, ‐15% and ‐40%, respectively; p<0.01 both), reduced adiponectin expression (‐20%; p<0.05), markedly reduced adiponectin release (‐60%; p<0.01), and substantially increased leptin (+60%; p<0.01) and interleukin‐6 (+50%; p<0.001) release. Interpretation/conclusions: The hepatokine FGF21 exerts weak lipogenic and anti‐adipogenic actions and marked adiponectin‐suppressive and leptin and interleukin‐6 release‐promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes. We analysed in vitro differentiated preadipocytes from 20 human donors treated with FGF21 or control cultures.

Dataset Information

Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity.

Publications

Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity.

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