Perturbation of the Monocyte Compartment in Human Obesity

Abstract

Circulating monocytes can be divided into classical (CM), intermediate (IM), and non-classical monocytes (NCM), and the classical monocytes also contain CD56+ monocytes and monocytic myeloid-derived suppressor cells (M-MDSC). The aim of the study was to evaluate the occurrence of the monocyte subpopulations in human obesity. Twenty-seven normal, 23 overweight, and 60 obese individuals (including 17 obese individuals with normal glucose tolerance and 27 with type 2 diabetes) were included into this study. Peripheral blood mononuclear cells were isolated from human blood, and surface markers to identify monocyte subpopulations were analyzed by flow cytometry. Obese individuals had higher numbers of total monocytes, CM, IM, CD56+ monocytes, and M-MDSCs. The number of CM, IM, CD56+ monocytes, and M-MDSCs, correlated positively with body mass index, body fat, waist circumference, triglycerides, C-reactive protein, and HbA1c, and negatively with high-density lipoprotein cholesterol. Individuals with obesity and type 2 diabetes had higher numbers of IM, NCM, and M-MDSCs, whereas those with obesity and impaired glucose tolerance had higher numbers of CD56+ monocytes. In summary, the comprehensive analysis of blood monocytes in human obesity revealed a shift of the monocyte compartment toward pro-inflammatory monocytes which might contribute to the development of low-grade inflammation in obesity, and immune-suppressive monocytes which might contribute to the development of cancer in obesity.

Keywords: CD16; CD56; macrophages; monocytes; myeloid suppressor cells (MDSC); obesity; subpopulation.

Figure 1

Quantification of classical, intermediate, and non-classical monocytes of normal, overweight, and obese individuals. (A) Representative dot plot of CD14 and CD16 expression on monocytes. (B) Absolute numbers of classical, intermediate, and non-classical monocytes of normal (n = 27), overweight (ow, n = 23), and obese (ob, n = 60) individuals. Scatter plots show mean ± SEM. (C–E) Correlation of classical monocyte numbers with BMI (C, n = 110), body fat (D, n = 108), and waist circumference (E, n = 101). (F–H) Correlation of intermediate monocyte numbers with BMI (F, n = 110), body fat (G, n = 108), and waist circumference (H, n = 101). (I) Absolute numbers of classical, intermediate, and non-classical monocytes of obese individuals with (Ob/T2D, n = 27) and without (Ob, n = 33) type 2 diabetes. Scatter plots show mean ± SEM.

Figure 2

Quantification of CD56+ monocytes of normal, overweight, and obese individuals. (A) Representative dot plot of CD14 and CD56 expression on monocytes. (B) Absolute numbers of CD56+ monocytes of normal (n = 27), overweight (ow, n = 23), and obese (ob, n = 60) individuals. Scatter plots show mean ± SEM. (C–E) Correlation of CD56+ monocyte numbers with BMI (C, n = 110), body fat (D, n = 108), and waist circumference (E, n = 101). (F) Absolute numbers of CD56+ monocytes of obese individuals with (n = 36) and without (n = 19) impaired glucose tolerance. Scatter plots show mean ± SEM.

Figure 3

Quantification of M-MDSCs of normal, overweight, and obese individuals. (A) Representative dot plot of CD14 and HLA-DR expression on monocytes. (B) Absolute numbers of M-MDSCs of normal (n = 21), overweight (ow, n = 22), and obese (ob, n = 37) individuals. Scatter plots show mean ± SEM. (C–E) Correlation of M-MDSC numbers with BMI (C, n = 80), body fat (D, n = 75), and waist circumference (E, n = 67). (F) Absolute numbers of M-MDSCs of obese individuals with (n = 19) and without (n = 18) impaired glucose tolerance. Scatter plots show mean ± SEM.

Figure 4

Perturbation of the monocyte compartment in human obesity. CM, classical monocytes; IM, intermediate monocytes; NCM, non-classical monocytes; MDSC, myeloid derived suppressor cells; BMI, body mass index; IGT, impaired glucose tolerance; T2D, type 2 diabetes.