In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds

TL;DR

Researchers developed a human fat cell model to study mitochondrial dysfunction and test drugs that could improve mitochondrial function in obesity.

Contribution

A novel in vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial metabolism and drug effects.

Findings

Lipid overload in adipocyte spheroids causes mitochondrial bioenergetic defects.

Rosiglitazone treatment improves mitochondrial function and adiponectin secretion in lipid-treated spheroids.

Matrigel embedding enhances mitochondrial network and respiration in adipocyte spheroids.

Abstract

Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, yet in vitro models to study adipocyte mitochondria remain limited. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks using thiazolidinedione-free medium. Matrigel embedding was incorporated into the protocol as it promoted mitochondrial network and respiration compared to scaffold-free conditions. Differentiated spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration, adiponectin secretion, and hormonal responsiveness. Lipid mixture administration during differentiation induced metabolic disturbances, including mitochondrial respiration failure, alongside increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria metabolism, providing a platform for mitochondria-focused research and drug discovery in obesity.

•Human adipocyte spheroids mimic mitochondrial metabolism in diverse states•Lipid overload induces mitochondrial bioenergetic defects in adipocyte spheroids•Early effects of PPARγ agonist include restored adipocyte mitochondrial respiration•This model supports research on mitochondrial biology and drug targeting

Human adipocyte spheroids mimic mitochondrial metabolism in diverse states

Lipid overload induces mitochondrial bioenergetic defects in adipocyte spheroids

Early effects of PPARγ agonist include restored adipocyte mitochondrial respiration

This model supports research on mitochondrial biology and drug targeting

Lipid; Human metabolism; Adipocyte; Mitochondria; Spheroid; Obesity

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