The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths

Abstract

Purpose of review: Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations.

Recent findings: Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, "M2-like" macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation. More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.

Keywords: Adaptive immunity; Adipose tissue; Ethnicity; Gender; Innate immunity; Obesity; Race.

Conflict of interest statement

Conflict of Interest Madhur Agrawal, Philip A. Kern, and Barbara S. Nikolajczyk declare that they have no conflicts of interest.

Figures

Fig. 1

Schematic representation of innate, adaptive, and bridging immune cells in adipose tissue. Obesity and chronic high-fat feeding the shifts resting immune system in adipose tissue to a pathogenic phenotype that produces a pro-inflammatory cytokine profile. Obese AT contains an increased number of M1 macrophages, B cells, Bregs, Th1 cells and Th17 cells (shown in open circles) and a decreased number of invariant natural killer T (iNKT) cells, M2 macrophages, eosinophils (Es), mast cells, Th2 cells, and Tregs (shown in gray circles). The inflammatory role of iNKT cells is debatable and the scientific community has recognized both pro- and anti-inflammatory activities of iNKT cells depending on the conditions [42, 43]. Cytokines, chemokines, IgG, and histamine, which control adipose tissue homeostasis, are listed next to respective cell types [30, 44]