Human Visceral Adipose Tissue Macrophages Are Not Adequately Defined by Standard Methods of Characterization

Abstract

Obesity is associated with a state of chronic low-grade inflammation both systemically and within specific tissues, including adipose tissue (AT). In murine models of obesity, there is a shift in the inflammatory profile of the AT immune cells, with an accumulation of proinflammatory M1 macrophages that surround the expanding adipocyte. However, much less is known about the immune cell composition and how to best define AT macrophages in humans. Objective. The goals of the current study were to determine the contribution of macrophages to the stromal vascular fraction (SVF) in lean versus obese human visceral AT (VAT); examine the expression of common M1, M2, and pan macrophage markers; and determine the association of specific macrophage types with known biomarkers of obesity-related cardiometabolic disease. Research Design and Methods. VAT biopsies were obtained from obese (n = 50) and lean (n = 8) patients during elective surgery. Adipocytes and SVF were isolated, and the SVF was subjected to flow cytometry analyses. Results. Our results indicate that VAT macrophages are increased in obesity and associate with biomarkers of CVD but that many macrophages do not fall into currently defined M1/M2 classification system based on CD206 receptor expression levels. Conclusions. VAT macrophages are increased in obese subjects, but the current markers used to define macrophage populations are inadequate to distinguish differences in human obesity. Further studies are needed to delineate the function of AT macrophages in the maintenance and progression of human AT inflammation in obesity.

Adipose tissue macrophages: Unique polarization and bioenergetics in obesity

“…Higher expression of CD206 correlated with another M2 marker CD163 and M1 markers CD11c, CD80, CD86, and HLA-DR. 32 The CD11c+CD206+ ATMs described by Wentworth et al 33 are another example of macrophages harboring both markers, existing on the continuum of M1/M2. It is interesting to note differential expression of other markers on human CD11c+ and CD206+ ATMs, such as the CD45 leukocyte marker, CD1c lipid antigen-presenting cell marker, and CD86 general antigen-presenting cell marker that likely assists with handling excess lipid.…”

Introductory Chapter: Unbearable Burden of the Diseases - Obesity

“…But researches and inventions in medicine show that the mechanism and etiology of obesity are not so simple. Reported studies showed that obesity pathogenesis is not only based on excess energy expenditure but also on the body's urge to fix and maintain the weight at an augmented value [9,11,[13][14][15]. This process would explain why obesity does not respond to long-lasting diet and exercise program or why there is no permanent reduction in weight even if there is a response [12].…”

Epigenetic treatment of dermatologic disorders

“…Nrf2‐activating compounds are becoming staple ingredients in topically applied skin‐conditioning creams and other formulations that mitigate skin damage (Ahmed, ; Ben‐Nun, ; Braidy et al, ; Burke, ; Davinelli, Nielsen, & Scapagnini, ; Gorini et al, ; Huang, Wang, Yang, Chou, & Fang, ; Kocot, Kiełczykowska, Luchowska‐Kocot, Kurzepa, & Musik, ; Kunnumakkara et al, ; Lephart, ; Ríos, Giner, Marín, & Recio, ; Rodríguez‐Luna et al, ; Simitzis, ; Vega et al, , ; Vollmer et al, ; Yang et al, ; Yokota, Yahagi, & Masaki, ), promote skin repair (Bellot et al, ; Davinelli, Nielsen, & Scapagnini, ; Ferreira & Gomes, ; Kim et al, ; Yang et al, ), and enhance diabetic‐associated wound healing (Bellot et al, ; Ben‐Nun, ; Cuadrado et al, ; Ferreira & Gomes, ; Gorini et al, ; Huang et al, ; Kim et al, ; Kocot et al, ; Kunnumakkara et al, ; Panahi et al, ; Ríos et al, ; Sanchez, Lancel, Boulanger, & Neviere, ; Vega et al, ; Vega et al, ; Vollmer et al, ). With respect to the latter, almost a third of the world's population is considered to be overweight or obese (González‐Muniesa et al, ) and the percentage is rising to epidemic proportions (Blaszczak et al, ; Severin, Sabbahi, Mahmoud, Arena, & Phillips, ). Weight gain is further magnified in pediatric and adolescent age groups (Wilkes et al, ).…”

“…With respect to the latter, almost a third of the world's population is considered to be overweight or obese (González-Muniesa et al, 2017) and the percentage is rising to epidemic proportions (Blaszczak et al, 2019;Severin, Sabbahi, Mahmoud, Arena, & Phillips, 2019). Weight gain is further magnified in pediatric and adolescent age groups (Wilkes et al, 2019).…”

“…Weight gain is further magnified in pediatric and adolescent age groups (Wilkes et al, 2019). Although obesity is comorbid with a wide range of chronic noncommunicable diseases, it is highly associated with diabetes type 2 (Blaszczak et al, 2019;González-Muniesa et al, 2017;Severin et al, 2019;Wilkes et al, 2019)-an insidious disease whose prevalence, not surprisingly, is also increasing proportionately in all population groups (Cho et al, 2018).…”