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

K Verboven,J W Jocken,S Wetzels,M Bijnen,K Gaens,D Hansen,G H Goossens,C D Stehouwer,K Wouters,C G Schalkwijk,E E Blaak

doi:10.1038/s41598-018-22962-x

K Verboven, J W Jocken + Show 9 more

Open Access

https://doi.org/10.1038/s41598-018-22962-x

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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.

Highlights

IntroductionDuring the development of obesity, adipose tissue (AT) expansion frequently results in adipocyte hypertrophy (i.e. enlargement of the adipocyte), which is a known stressor for adipocytes[1]
During the development of obesity, adipose tissue (AT) expansion frequently results in adipocyte hypertrophy, which is a known stressor for adipocytes[1]
As reported previously[7], obese individuals have an attenuated basal lipolysis in both subcutaneous adipose tissue depot (SCAT) and visceral AT (VAT), and a decreased maximal atrial natriuretic peptide (ANP)- and ISO-mediated lipolytic responsiveness in SCAT, compared to age-matched lean individuals. We demonstrate that this altered AT phenotype was further characterized by adipocyte hypertrophy and an increased immune cell infiltration, especially in the VAT

Summary

Introduction

During the development of obesity, adipose tissue (AT) expansion frequently results in adipocyte hypertrophy (i.e. enlargement of the adipocyte), which is a known stressor for adipocytes[1]. Different immune cells are activated within hypertrophic AT (in case of resident immune cells) or attracted toward necrotic/apoptotic hypertrophic adipocytes, especially in the visceral AT (VAT), mainly based on rodent studies[10,11] This VAT inflammation was proposed to be the strongest correlate of IR in human obesity[12,13]. The cross-talk and dynamics of immune cells initiating and orchestrating AT inflammation and an impaired lipid metabolism in different AT depots are incompletely understood in the obese non-diabetic or type 2 diabetic state. It is still an ongoing debate whether an impaired AT lipolysis or inflammation, or an interaction between both, is a cause or rather a consequence of IR in the obese state. We studied subcutaneous and visceral AT morphology (adipocyte size), ex vivo lipolysis and immune cell populations (flow cytometry) in relation to whole-body IR in obese non-diabetic and type 2 diabetic (T2DM) men, compared with age-matched lean men

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