Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase.

Abstract

Resveratrol is attracting much interest because of its potential to decrease body weight and increase life span, influencing liver and muscle function by increasing mitochondrial mass and energy expenditure. Even though resveratrol was already shown to reduce the adipose tissue mass in animal models, its effects on mitochondrial mass and network structure in adipocytes have not yet been studied. For this purpose, we investigated the effect of resveratrol on mitochondrial mass increase and remodeling during adipogenic differentiation of two in vitro models of adipocyte biology, the murine 3T3-L1 cell line and the human SGBS cell strain. We confirm that resveratrol inhibits lipogenesis in differentiating adipocytes, both mouse and human. We further show that this is linked to inhibition of the normally observed mitochondrial mass increase and mitochondrial remodeling. At the molecular level, the anti-lipogenic effect of resveratrol seems to be mediated by a blunted expression increase and an inhibition of acetyl-CoA carboxylase (ACC). This is one of the consequences of an inhibited insulin-induced signaling via Akt, and maintained signaling via AMP-activated protein kinase. The anti-lipogenic effect of resveratrol is further modulated by expression levels of mitochondrial ATAD3, consistent with the emerging role of this protein as an important regulator of mitochondrial biogenesis and lipogenesis. Our data suggest that resveratrol acts on differentiating preadipocytes by inhibiting insulin signaling, mitochondrial biogenesis, and lipogenesis, and that resveratrol-induced reduction of mitochondrial biogenesis and lipid storage contribute to adipose tissue weight loss in animals and humans.

• Authors: Shuijie Li, Célia Bouzar, Cécile Cottet-Rousselle, Ivana Zagotta, Frédéric Lamarche, Martin Wabitsch, Malgorzata Tokarska-Schlattner, Pamela Fischer-Posovszky, Uwe Schlattner, Denis Rousseau
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1857 Issue 6 Pg. 643-52 (Jun 2016) ISSN: 0006-3002 [Print] Netherlands
• PMID: 26968895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Atad3a protein, mouse
• Insulin
• Mitochondrial Proteins
• Stilbenes
• Proto-Oncogene Proteins c-akt
• AMP-Activated Protein Kinases
• Adenosine Triphosphatases
• ATPases Associated with Diverse Cellular Activities
• Acetyl-CoA Carboxylase
• Resveratrol

Topics

• 3T3-L1 Cells
• AMP-Activated Protein Kinases (metabolism)
• ATPases Associated with Diverse Cellular Activities
• Acetyl-CoA Carboxylase (metabolism)
• Adenosine Triphosphatases (metabolism)
• Adipocytes (cytology, drug effects, metabolism)
• Adipogenesis (drug effects)
• Animals
• Antioxidants (pharmacology)
• Blotting, Western
• Cell Line
• Dose-Response Relationship, Drug
• Humans
• Insulin (metabolism)
• Lipogenesis (drug effects)
• Mice
• Mitochondria (drug effects, metabolism)
• Mitochondrial Proteins (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Resveratrol
• Signal Transduction (drug effects)
• Stilbenes (pharmacology)