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

May 6, 2021FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Ellagic acid promotes the conversion of white fat to beige fat by regulating energy production and cell maintenance

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Abstract

Ellagic acid (EA) induces the trans-differentiation of white adipocytes to beige adipocytes in cold-exposed mice.

EA promotes the expression of several key factors associated with brown and beige adipose tissue, including UCP1, PRDM16, and PGC1α.
Mitochondrial dynamics-related factors such as SIRT3 and DRP1 are also increased by EA treatment.
The browning effect of EA is inhibited by a DRP1 inhibitor, indicating its role in this process.
SIRT3 knockdown reduces the impact of EA, suggesting its involvement in the beige remodeling of white adipose tissue.

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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.

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

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