Contributions of innate type 2 inflammation to adipose function

Abstract

A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

Obesity-induced reduction of adipose eosinophils is reversed with low-calorie dietary intervention

“…Eosinophils, and other Th2‐like innate immune cells, have risen to the forefront of recent AT research. Many studies indicate eosinophils and innate lymphoid type 2 cells are key players in maintaining AT homeostasis, but these studies are not without their caveats (Bolus and Hasty ; Knights et al. ).…”

“…Eosinophils, and other Th2-like innate immune cells, have risen to the forefront of recent AT research. Many studies indicate eosinophils and innate lymphoid type 2 cells are key players in maintaining AT homeostasis, but these studies are not without their caveats (Bolus and Hasty 2018;Knights et al 2018). While high levels of systemically elevated eosinophils have been shown to protect against the effects of high-fat diet (HFD)-induced obesity (Wu et al 2011;Molofsky et al 2013;Hussaarts et al 2015), restoring AT eosinophils to physiological levels has not recapitulated such beneficial effects (Bolus et al 2017).…”

The many secret lives of adipocytes: implications for diabetes

“…Traditionally, the proinflammatory cell population is referred to as 'M1' macrophages, and the remodelling cells as 'M2' macrophages. Even though these are very heterogeneous populations that fall into many additional subcategories, these functional definitions are still very useful [9]. Additional innate immune populations have been identified in adipose tissue, such as neutrophils, mast cells and eosinophils.…”

Analysis of the percentages of monocyte subsets and ILC2s, their relationships with metabolic variables and response to hypocaloric restriction in obesity

“…Recent evidences indicate that ILCs are involved in the progression of several metabolic diseases. These cells promote obesity, and are involved in adipose tissue inflammation [23,24]. Nevertheless, group 2 innate lymphoid cells (ILC2s), anti-obese immune regulators in AT, secrete anti-inflammatory cytokines, promote polarization into M2 macrophages, eosinophil regulating adaptive immunity, limiting obesity and promoting the browning of WAT [25].…”