Temperature-Dependent Effects of Eicosapentaenoic Acid (EPA) on Browning of Subcutaneous Adipose Tissue in UCP1 Knockout Male Mice

Author(s)/Creator(s)

Latha RamalingamFollow

ORCID

Latha Ramalingam: 0000-0002-4856-7327

Document Type

Article

Date

5-2023

Keywords

beige adipocytes, eicosapentaenoic acid, environmental temperature, obesity, uncoupling protein 1

Disciplines

Molecular, Genetic, and Biochemical Nutrition

Description/Abstract

Uncoupling protein 1 (UCP1) plays a central role in thermogenic tissues by uncoupling cellular respiration to dissipate energy. Beige adipocytes, an inducible form of thermogenic cells in subcutaneous adipose tissue (SAT), have become a major focus in obesity research. We have previously shown that eicosapentaenoic acid (EPA) ameliorated high-fat diet (HFD)-induced obesity by activating brown fat in C57BL/6J (B6) mice at thermoneutrality (30 °C), independently of UCP1. Here, we investigated whether ambient temperature (22 °C) impacts EPA effects on SAT browning in wild-type (WT) and UCP1 knockout (KO) male mice and dissected underlying mechanisms using a cell model. We observed resistance to diet-induced obesity in UCP1 KO mice fed HFD at ambient temperature, with significantly higher expression of UCP1-independent thermogenic markers, compared to WT mice. These markers included the fibroblast growth factor 21 (FGF21) and sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b), suggesting the indispensable role of temperature in beige fat reprogramming. Surprisingly, although EPA induced thermogenic effects in SAT-derived adipocytes harvested from both KO and WT mice, EPA only increased thermogenic gene and protein expression in the SAT of UCP1 KO mice housed at ambient temperature. Collectively, our findings indicate that the thermogenic effects of EPA, which are independent of UCP1, occur in a temperature-dependent manner.

Recommended Citation

Zu Y, Pahlavani M, Ramalingam L, Jayarathne S, Andrade J, Scoggin S, Festuccia WT, Kalupahana NS, Moustaid-Moussa N. Temperature-Dependent Effects of Eicosapentaenoic Acid (EPA) on Browning of Subcutaneous Adipose Tissue in UCP1 Knockout Male Mice. Int J Mol Sci. 2023 May 13;24(10):8708. doi: 10.3390/ijms24108708. PMID: 37240054; PMCID: PMC10218247.

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This work is licensed under a Creative Commons Attribution 4.0 International License.