Diabetes Metab J.  2023 Mar;47(2):164-172. 10.4093/dmj.2022.0270.

Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation

• Bae EJ
• Park BH

• KMID: 2540513
• DOI: http://doi.org/10.4093/dmj.2022.0270

Abstract

Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

Keyword

Adipose tissue; Eosinophils; Inflammation; Macrophages

Figure

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  Fig. 1. Inhibition of adipose tissue inflammation by sirtuin 6 (Sirt6). In adipocytes, Sirt6 increases the production of the type 2 cytokine interleukin 4 (IL-4) to promote M2-type macrophage polarization in a paracrine manner. In eosinophils, Sirt6 forms a ternary complex with GATA binding protein 1 (GATA-1) and p300 acetyltransferase to positively regulate GTAT-1 transcriptional activity. In macrophages, Sirt6 inhibits the nuclear factor-κB (NF-κB)–IL-6–signal transducer and activator of transcription 3 (STAT3) signaling axis and suppresses M1-type macrophage polarization in an autocrine manner. Conversely, Sirt6 activates the phosphoinositide 3-kinases (PI3K)-Akt pathway and promotes M2-type macrophage polarization.

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