The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Abstract

Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct environmental metabolic cues. This may be of particular importance in the setting of obesity, where both liver and adipose tissue are faced with a high metabolic burden. In the first part of this review we will discuss current knowledge regarding macrophage dynamics in both adipose tissue and liver in obesity. Then in the second part, we will highlight data linking macrophage metabolism to functional phenotype with an emphasis on macrophage activation in metabolic disease. The importance of understanding how tissue niche influences macrophage function in obesity will be highlighted. In addition, we will identify important knowledge gaps and outstanding questions that are relevant for future research in this area and will facilitate the identification of novel targets for therapeutic intervention in associated metabolic diseases.

The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)

“…In major metabolic diseases, the onset is characterized by alteration of peripheral macrophage number and functional phenotype, especially in the hepatic and obese tissue [ 57 ]. In increased adipose tissue, researchers found high levels of macrophages, mainly resident adipose tissue macrophages (ATMs), which were detected in clusters named crown-like structures (CLS) [ 58 , 59 ].…”

Metabolic health and lifestyle medicine should be a cornerstone of future pandemic preparedness

“…Considering that recent estimates in the United States suggest that less than 20% of adults have optimal metabolic health, 30 a sliding scale exists that could still place the majority of adults at some degree of increased risk of susceptibility to certain infectious diseases. More broadly, the comorbidities associated with increased risk of severe COVID‐19 can also all be characterized as having the presence of low‐grade chronic inflammation, 31‐34 as well as the presence of many of the hallmarks of aging, 35 which together are pathognomonic for the process of “inflammaging.” 36,37 Indeed, a group of researchers with significant experience in the of field of aging and biomarkers of biological age have released a preprint proposing that COVID‐19 is an emergent disease of aging 38 . Previous studies of patients with the related SARS‐CoV‐1 and MERS (Middle East Respiratory Syndrome) coronaviruses also suggest that in addition to age, similar comorbidities to those that predispose to worse outcomes in COVID‐19 played a role in mortality risk 39‐42 .…”

<p>Changes in Function and Dynamics in Hepatic and Splenic Macrophages in Non-Alcoholic Fatty Liver Disease</p>

“…Alternatively, it was also reported from other studies that there was no increasing in total number of Mf. [24][25][26][27][28] In this study, with progression of NAFLD, the number of the total hepatic Mfs tended to increase; however, there were no significant differences in the number between the liver and the spleen (Figure 1). In contrast, the percentage of the M2type (matured) hepatic Mfs/total hepatic Mfs significantly increased ( Figure 3C).…”