Ann Pediatr Endocrinol Metab.  2021 Mar;26(1):1-13. 10.6065/apem.2040188.094.

Role of obesity-induced inflammation in the development of insulin resistance and type 2 diabetes: history of the research and remaining questions

• Kim J
• Lee J

• KMID: 2514146
• DOI: http://doi.org/10.6065/apem.2040188.094

Abstract

The prevalence of obesity has increased alarmingly both worldwide and in Korea. This has also dramatically increased the prevalence of chronic obesity-associated diseases, including type 2 diabetes (T2D). Extensive studies on the molecular etiology of T2D have revealed several potential mechanisms by which obesity induces the development of insulin resistance and T2D. One of these is low-grade chronic inflammation. Studies hinting at the existence of this phenomenon were first published about 30 years ago. Ten years later, several seminal papers confirmed its existence, which then led to a rapid and massive escalation of research in this field. Today, the notion that obesity-induced inflammation mediates T2D is now well-accepted. This paper will review the key developments in this field, including the discovery that obesity-induced inflammation and insulin resistance is mainly regulated by adipose tissue-resident immune cells, particularly those in visceral adipose tissue. This review further details the research areas, including (1) the obesity-related factors that induce adipose tissue macrophage (ATM) inflammation, (2) the precise effector functions by which adipose tissue immune cells promote insulin resistance, (3) whether there are early immunological events that have an outsize effect on later events and could be targeted to arrest the development of insulin resistance, (4) the roles played by nonimmunological functions of ATMs and other immune cells, and (5) whether there are noncanonical immune responses to obesity (i.e., immune responses that are unique to obesity and cannot be detected by following the discoveries in the classical immunity field).

Keyword

Obesity; Inflammation; Immune cells; Adipose tissue; Insulin resistance; Type 2 diabetes

Figure

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  Fig. 1. Treatments for type 2 diabetes. CB1, cannabinoid 1; TZD, thiazolidinedione; DPP-4, dipeptidyl peptidase-4; SGLT-2, sodium glucose cotransporter-2.

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  Fig. 2. The number of publications in PubMed using keywords as "obesity" and "inflammation." TNF, tumor necrosis factor; T2D, type 2 diabetes; ATMs, adipose tissue macrophages.

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  Fig. 3. Regulation of adipose tissue inflammation in obesity.

Reference

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