Sex-specific Association Between Adipose Tissue Inflammation and Vascular and Metabolic Complications of Obesity

Abstract

Abstract Context Adipose tissue (AT) inflammation predisposes to insulin resistance and metabolic syndrome in obesity. Objective To investigate the association between adipocyte size, AT inflammation, systemic inflammation, and metabolic and atherosclerotic complications of obesity in a sex-specific manner. Design Cross-sectional cohort study. Setting University hospital in the Netherlands. Participants A total of 302 adult subjects with a body mass index (BMI) ≥ 27 kg/m2. Main outcome measures We obtained subcutaneous abdominal fat biopsies and systematically assessed, in a sex-specific manner, associations of several parameters of AT inflammation (including adipocyte size, macrophage content, crown-like structures, and gene expression) to biomarkers of systemic inflammation, leukocyte number and function, and to the presence of metabolic syndrome, insulin resistance, and carotid atherosclerotic plaques, assessed with ultrasound. Results Adipocyte size was associated with metabolic syndrome and AT macrophage content with insulin resistance. In contrast, none of the AT parameters was associated with carotid atherosclerosis, although mRNA expression of the anti-inflammatory IL-37 was associated with a lower intima-media thickness. We revealed profound sex-specific differences, with an association between BMI and adipocyte size, and between adipocyte size and metabolic syndrome in men only. Also, only men showed an association between adipocyte size, AT expression of leptin and MCP-1, and AT macrophage numbers, and between AT inflammation (crown-like structure number) and several circulating inflammatory proteins, including high specificity C-reactive protein, and IL-6. Conclusions Inflammation in abdominal subcutaneous adipose tissue is more related to the metabolic than the atherosclerotic complications of obesity, and there are profound sex-specific differences in the association between BMI, adipocyte size, AT inflammation, and systemic inflammation, which are much stronger in men than women.