Ellagic acid induces beige remodeling of white adipose tissue by controlling mitochondrial dynamics and SIRT3

FASEB J. 2021 Jun;35(6):e21548. doi: 10.1096/fj.202002491R.

Abstract

To determine whether ellagic acid (EA) induces the "beige remodeling" of white adipose tissue (WAT), we treated cold-exposed mice and mouse stromal vascular fraction (SVF) cells with EA, a phytochemical abundant in fruits and vegetables, in particular berries. We then investigated the mechanism of EA in beige remodeling with a particular focus on DRP1-mediated mitochondrial fission and SIRT3. EA induced the trans-differentiation of white adipocytes to beige adipocytes by promoting the expression of UCP1 and other brown and beige adipocytes/fat factors (PRDM16, UCP1, PGC1α, CD137, and TBX1) and mitochondrial dynamics-related factors (SIRT3, NRF1, CPT1β, DRP1, and FIS1) in 3T3-L1/SVF cells, and these were confirmed in the inguinal WAT of a cold-exposed mouse model. The browning effect of EA was abolished by a potent DRP1 inhibitor Mdivi-1 or SIRT3 knockdown, suggesting that EA induces beige remodeling of WAT by regulating the mitochondrial dynamics and SIRT3.

Keywords: beige remodeling; ellagic acid; mitochondrial fission; sirtuin-3; thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Beige / cytology
  • Adipocytes, Beige / drug effects
  • Adipocytes, Beige / physiology*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / physiology*
  • Animals
  • Ellagic Acid / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Dynamics*
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*
  • Thermogenesis

Substances

  • Sirt3 protein, mouse
  • Ellagic Acid
  • Sirtuin 3