The Role of T Cells in Obesity-Associated Inflammation and Metabolic Disease

Abstract

Chronic inflammation plays a critical role in the development of obesity-associated metabolic disorders such as insulin resistance. Obesity alters the microenvironment of adipose tissue and the intestines from anti-inflammatory to pro-inflammatory, which promotes low grade systemic inflammation and insulin resistance in obese mice. Various T cell subsets either help maintain metabolic homeostasis in healthy states or contribute to obesity-associated metabolic syndromes. In this review, we will discuss the T cell subsets that reside in adipose tissue and intestines and their role in the development of obesity-induced systemic inflammation.

Keywords: Insulin resistance; Metabolic diseases; Obese mice; Obesity-associated inflammation; T cells.

Figure 1. Changes in T cell subsets in adipose tissue and intestine during high-fat diet feeding.

Adipose tissue: In lean AT, resident immune cells, such as M2 ATMs, Th2 cells, Treg, and iNKT cells support adipocytes physiology. Together these cells secrete anti-inflammatory cytokines such as IL-4 and IL-10, which inhibit inflammation. During obesity, accumulation of M1 ATMs, CD8⁺ T cells, Th1 cells, and γδ T cells results in excess production of pro-inflammatory cytokines such as TNF-α, IL-6. IFN-γ, and IL-1β. These cytokines contribute to systemic inflammation and insulin resistance. Intestine: In health, the intestinal immune environment is dominated by anti-inflammatory immune cells. These cells include IL-10 producing Treg, protective IL-17 producing Th17 cells, αβ IELs T cells, and γδ IELs T cells. During obesity, the number of pathogenic IFN-γ producing Th1 cells, CD8⁺ T cells, IL-17 producing γδ IELs T cells, and CD44⁺ MAIT cells is increased. These proinflammatory changes contribute to intestinal dysfunction, dysbiosis, and systemic inflammation through enhanced leakage of LPS.