Do adipose tissue macrophages promote insulin resistance or adipose tissue remodelling in humans?

Abstract

In diet induced and genetically obese rodent models, adipose tissue is associated with macrophage infiltration, which promotes a low grade inflammatory state and the development of insulin resistance. In humans, obesity is also closely linked with macrophage infiltration in adipose tissue, a pro-inflammatory phenotype and insulin resistance. However, whether macrophage infiltration is a direct contributor to the development of insulin resistance that occurs in response to weight gain, or is a later consequence of the obese state is unclear. There are a number of concomitant changes that occur during adipose tissue expansion, including the number and size of adipocytes, the vasculature and the extracellular matrix. In this review, we will examine evidence for and against the role of macrophage recruitment into adipose tissue in promoting the development of insulin resistance in rodents and humans, as well as discuss the emerging role of macrophages in mediating healthy adipose tissue expansion during periods of caloric excess.

Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes

“…Macrophages are also believed to be an important contributor of insulin resistance . Macrophages account for up to 40% of adipose cell content in individuals with obesity compared with only 10% in lean humans and secrete pro‐inflammatory cytokines such as interleukin (IL) 6, IL1β, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and tumour necrosis factor α (TNFα) . In addition, macrophage infiltration in adipose tissue leads to adipose tissue dysfunction, thereby contributing to the altered secretion pattern of adipokines.…”

“…56,57 Macrophages account for up to 40% of adipose cell content in individuals with obesity compared with only 10% in lean humans 58 and secrete pro-inflammatory cytokines such as interleukin (IL) 6, IL1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumour necrosis factor α (TNFα). 59 In addition, macrophage infiltration in adipose tissue leads to adipose tissue dysfunction, thereby contributing to the altered secretion pattern of adipokines. It is interesting to note that the secretion pattern of adipokines and cytokines not only changes with increased adiposity but also varies across fat depots.…”

Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes

“…There is a limited understanding of how obesity-induced inflammation in AT is triggered. However, potential mechanisms identified include dysregulation of fatty acids homeostasis, increased adipose cell size and death, local hypoxia, mitochondrial dysfunction, ER stress, and mechanical stress (Figure 2) (Heilbronn and Liu, 2014;Reilly and Saltiel, 2017). These mechanisms are recognized as the link between chronic caloric excess and AT inflammation or as factors that may perpetuate chronic tissue inflammation (Burhans et al, 2018).…”

“…Increased adipocyte size is characterized by a higher rate of adipocyte death and macrophage recruitment. Larger adipocytes exhibit an altered chemoattractant and immunerelated proteins secretion that may promote pro-inflammatory macrophage infiltration (Jernas et al, 2006;Heilbronn and Liu, 2014). Most of these infiltrated macrophages surround necrotic adipocytes and form crown-like structures.…”

Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids

“…Antioxidants have been suggested as promising agents for treatment of NAFLD and its related disorders (Abenavoli et al, 2012;Romano et al, 2013;Parhiz et al, 2015). Inflammation, the central point of the initiation of NAFLD, is believed to be caused by hypoxia in overcrowded adipocytes of obese individuals (Heilbronn and Liu, 2014). In fact, oxidative stress and inflammation generally come side by side in disease states like obesity (Codoñer-Franch et al, 2011;Fernández-Sánchez et al, 2011;Bondia-Pons et al, 2012) and hepatic diseases (de Andrade et al, 2015).…”