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Review
. 2021 Jun 2;22(11):6025.
doi: 10.3390/ijms22116025.

Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

Masaki Kobayashi  1 , Yusuke Deguchi  1 , Yuka Nozaki  1 , Yoshikazu Higami  1   2
Affiliations
Review

Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

Masaki Kobayashi et al. Int J Mol Sci. .

Abstract

Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.

Keywords: PGC-1α; caloric restriction; obesity; white adipose tissue.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Regulation of PGC-1α in white adipose tissue (WAT) and its impact on whole-body metabolism. In obese WAT, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is transcriptionally silenced by p53 and tumor necrosis factor α (TNFα), and suppressed at the activity level by interacting with receptor-interacting protein 140 (RIP140). This triggers a decrease in the amount of mtDNA and expression of mitochondrial genes in WAT, resulting in obesity-related pathology (e.g., insulin resistance and glucose intolerance). In WAT, during caloric restriction (CR), PGC-1α is transcriptionally upregulated by sterol regulatory element-binding protein 1c (SREBP-1c) and via the SREBP-1c-fibroblast growth factor 21 (FGF21) axis, and post-translationally activated by AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1). This induces fatty acid (FA) synthesis, in addition to increasing mtDNA and mitochondrial gene expression in WAT, resulting in efficient energy metabolism in the whole body.
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