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.

Enrichment of Tc1 cells and T cell resistance to suppression are associated with dysglycemia in the visceral fat in human obesity

“…25 We first confirmed previous reports indicating that adipocyte morphology is altered in obesity regardless of the presence of diabetes. 26 Indeed, the size of adipocytes in the VAT of obese patients was double compared with LC, with no differences observed between OB-ND and OB-D patients (data not shown). Increased frequency of total T cells was observed in the VAT of obese patients, regardless of the presence of diabetes, while no differences in the frequency of CD4 and CD8 T cells were evident (online supplementary figure S2 and figure 1A,B).…”

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

“…Cell motility was then tracked by video microscopy (n = 40 cells per group). In obesity, although stimulated lipolysis induced by activation of adrenergic receptors decreases, basal lipolysis is heightened (Duncan et al, 2007;Verboven et al, 2018). Moreover, adipocyte EV contain adipokines, in particular, leptin (Table EV2), which has been shown to possess pro-tumoral properties in melanoma models (Amjadi et al, 2016) and be associated with an increased risk of lymph node metastasis in melanoma patients (Oba et al, 2016).…”

Adipocyte vesicles: ‘all-in-one’ packages that stimulate tumor mitochondrial metabolism and dynamics

“…In experimental conditions using equal quantities of vesicles, obese adipocyte EV convey higher levels of FA, which increases lipid accumulation in melanoma cells. In obesity, although stimulated lipolysis induced by activation of adrenergic receptors decreases, basal lipolysis is heightened (Duncan et al, 2007;Verboven et al, 2018). This process may increase FA release and, consequently, a higher availability of these substrates for tumor cells.…”