Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans

Abstract

Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45⁺ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.

Figure 1

Adipocyte size distribution. The frequency of small (<50 µm), medium (50–69 µm), large (70–89 µm) and very large (>90 µm) adipocytes was determined in SCAT (A) and VAT (B) of lean (black bars), obese (white bars) and obese diabetic (white squared bars) individuals. Obese groups clearly had higher proportions of large and very large adipocytes in combination with smaller proportions of small and medium size adipocytes, resulting in a higher mean adipocytes size compared to lean individuals both in SCAT (p < 0.001 for obese individuals and p < 0.01 for obese diabetic individuals) and VAT (p < 0.001 for both obese groups) Data are means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.