Innate Immune System Orchestrates Metabolic Homeostasis and Dysfunction in Visceral Adipose Tissue During Obesity

Abstract

Arising incidence of metabolic disorders and related diseases caused by obesity is a global health concern. Elucidating the role of the immune system in this process will help to understand the related mechanisms and develop treatment strategies. Here, we have focused on innate immune cells in visceral adipose tissue (VAT) and summarized the roles of these cells in maintaining the homeostasis of VAT. Furthermore, this review reveals the importance of quantitative and functional changes of innate immune cells when the metabolic microenvironment changes due to obesity or excess lipids, and confirms that these changes eventually lead to the occurrence of chronic inflammation and metabolic diseases of VAT. Two perspectives are reviewed, which include sequential changes in various innate immune cells in the steady state of VAT and its imbalance during obesity. Cross-sectional interactions between various innate immune cells at the same time point are also reviewed. Through delineation of a comprehensive perspective of VAT homeostasis in obesity-induced chronic inflammation, and ultimately metabolic dysfunction and disease, we expect to clarify the complex interactive networks among distinct cell populations and propose that these interactions should be taken into account in the development of biotherapeutic strategies.

Possible connection between intestinal tuft cells, ILC2s and obesity

“…HFD induces systemic low-grade chronic inflammation in animal models and humans. ILC2s work as a bridge linking epithelial cells and the immune system to promote immunity and metabolic homeostasis (103). In adipose tissue, ILC2s induce the type 2 cytokines IL-5 or IL-13 and increase eosinophils numbers, and M2 macrophages stimulate inflammation, which promotes immunity and metabolic homeostasis and curbs obesity (104,105).…”

Impact of obesity‑associated myeloid‑derived suppressor cells on cancer risk and progression (Review)

“…Thus, MDSCs limit the hyperactivation of pro-inflammatory cells and reduce tissue damage ( 75 ). In obesity conditions, maintaining immune homeostasis is crucial to avoid or prevent adipose tissue dysfunction ( 76 ). Obesity is associated with metabolic disorders such as diabetes, which is characterized by high glucose levels resulting from the inability of insulin to suppress hepatic glucose production ( 77 ).…”

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

“…In contrast, BAT, which has excess mitochondria, is the primary succinate-metabolizing tissue [ 338 ]. GPR91deletion in myeloid cells protected mice from obesity on HFD, but these mice showed impaired glucose tolerance and insulin sensitivity [ 335 , 340 , 341 ]. GPR91 −/− myeloid cells had decreased anti-inflammatory response to type 2 cytokines, including those associated with diet-induced obesity [ 340 ].…”