Hypertrophied human adipocyte spheroids as in vitro model of weight gain and adipose tissue dysfunction

Abstract

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What's up with WAT: attempting to mimic adipose tissue in vitro

“…Adipogenesis occurred along the vasculature, and prevention of vascular sprouting significantly reduced spheroid growth. Traditional two-dimensional cell culture and spheroids grown without Matrigel did not result in vasculature development and produced much smaller spheroids and adipocytes (Ioannidou et al 2022). Taken together, the HUVAS method developed in the current report (Ioannidou et al 2022) improves on many key features of WAT biology, including vasculature, extra cellular matrix, large unilocular adipocytes and adipokine secretion.…”

“…Another effect of obesity-associated WAT inflammation is that basal lipolysis is increased but resistant to stimulated lipolysis (Crewe et al 2017;Stenkula & Erlanson-Albertsson, 2018). Importantly, both increased basal lipolysis and impaired stimulated lipolysis were apparent in hypertrophied HUVAS (Ioannidou et al 2022). Additionally, WAT insulin resistance hinders the ability of insulin to suppress lipolysis and stimulate fatty acid and glucose uptake, ultimately contributing to systemic metabolic dysfunction.…”

“…The authors describe a way to mimic obesity-associated adipocyte hypertrophy and subsequent cellular dysfunction. This new model is called human unilocular vascularized adipocyte spheroids (HUVAS) and represents a major advancement in the ability to perform mechanistic in vitro analysis of human WAT in health and obesity (Ioannidou et al 2022).…”

“…Inflammation is one of the early responses to hypertrophy and results partly from the accumulation and activation of macrophages, which secrete inflammatory cytokines like interleukin-6 and monocyte chemotactic protein-1. These inflammatory responses were evident in hypertrophied HUVAS (Ioannidou et al 2022), but the macrophage response is unclear and would be interesting to explore since SVF used to differentiate HUVAS would contain immune cells.…”

The physiology of obesity: from mechanisms to medicine (M2M). Part one

“…They extend their work and study the effect in humans -the corresponding depot produces heat directly via lipolysis, generating heat in response to β-adrenergic stimulation. Ioannidou et al (2022), in their techniques paper, introduces the human unilocular vascularized adipocyte spheroid for the differentiation and culturing of human adipocytes. The model offers the ability to study larger lipid droplets and the development of key features of adipocyte dysfunction (impaired lipolysis and insulin resistance).…”