Polarization of Macrophages in Human Adipose Tissue is Related to the Fatty Acid Spectrum in Membrane Phospholipids

Abstract

Residential macrophages in adipose tissue play a pivotal role in the development of inflammation not only within this tissue, but also affect the proinflammatory status of the whole body. Data on human adipose tissue inflammation and the role of macrophages are rather scarce. We previously documented that the proportion of proinflammatory macrophages in human adipose tissue correlates closely with non-HDL cholesterol concentrations. We hypothesized that this is due to the identical influence of diet on both parameters and decided to analyze the fatty acid spectrum in cell membrane phospholipids of the same individuals as a parameter of the diet consumed. Proinflammatory and anti-inflammatory macrophages were isolated from human adipose tissue (n = 43) and determined by flow cytometry as CD14+CD16+CD36high and CD14+CD16−CD163+, respectively. The spectrum of fatty acids in phospholipids in the cell membranes of specimens of the same adipose tissue was analyzed, and the proportion of proinflammatory macrophage increased with the proportions of palmitic and palmitoleic acids. Contrariwise, these macrophages decreased with increasing alpha-linolenic acid, total n-3 fatty acids, n-3/n-6 ratio, and eicosatetraenoic acid. A mirror picture was documented for the proportion of anti-inflammatory macrophages. The dietary score, obtained using a food frequency questionnaire, documented a positive relation to proinflammatory macrophages in individuals who consumed predominantly vegetable fat and fish, and individuals who consumed diets based on animal fat without fish and nut consumption. he present data support our hypothesis that macrophage polarization in human visceral adipose tissue is related to fatty acid metabolism, cell membrane composition, and diet consumed. It is suggested that fatty acid metabolism might participate also in inflammation and the risk of developing cardiovascular disease.

Rewiring of Lipid Metabolism in Adipose Tissue Macrophages in Obesity: Impact on Insulin Resistance and Type 2 Diabetes

“…The inflammatory phenotype of human ATMs is correlated with the FA spectrum of membrane PL, and SFA and PUFA content share a positive and negative association, respectively, with the proportion of these macrophages in obese AT [110]. The SFA to PUFA ratio has also been implicated in ER stress response, and decreased ER saturation and rigidification by inhibition of the de novo PC synthesis pathway, which preferentially selects and binds SFA to PC, has been shown to ameliorate ER stress in BMDMs despite palmitate exposure [11].…”

Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model

“…A positive association between insulin resistance and enriched palmitic acid and depleted essential n-3 PUFA in adipose tissue has also been found. In addition, alterations in fatty acid profiles in visceral adipose tissue membrane phospholipids are related to intracellular metabolism and macrophage polarization [ 26 ]. In our previous human study, profiles of palmitic and palmitoleic acid in WAT correlated positively with the proportion of pro-inflammatory macrophages and negatively with the n-3 PUFA profile, correlations connected with chronic inflammation in adipose tissue.…”

A review on the biology and properties of adipose tissue macrophages involved in adipose tissue physiological and pathophysiological processes

“… Hybrid M1/M2 macrophages • CD11c + CD206 + [ 47 ] • F4/80 hi CD11c + CD206 + [ 44 ] ATMs phenotype isolated from obese mice [ 44 ]. Macrophages in human visceral adipose • CD14 + CD16 + CD36 high [ 48 ] • CD14 + CD16 − CD163 + Proinflammatory macrophages Anti-inflammatory macrophages Macrophages with different phenotypes perform diverse functions in adipose tissue. MMe macrophages are driven by high levels of glucose, insulin, and palmitate through the p62 and PPARγ pathways, with surface markers such as ABCA1, CD36 and PLIN2.…”

“…CD11c + CD163 + ATMs have been confirmed to accumulate in both VAT and SAT of obese individuals and were found to be clearly correlated with body mass index and production of reactive oxygen species [ 27 ]. Proinflammatory and anti-inflammatory macrophages from human VAT have been determined by flow cytometry as CD14 + CD16 + CD36 high and CD14 + CD16 − CD163 + , respectively [ 48 ]. Macrophages in obese adipose tissue are CD11c + CD206 + , interpreted to be hybrid M1/M2 macrophages [ 47 ].…”