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Circadian reprogramming of adipose progenitor cells regulates intermittent fasting-mediated adipose tissue remodeling and metabolic improvement

ABSTRACT: White adipose tissue (WAT) fibrosis is a hallmark of dysfunctional WAT that is directly linked to obesity- associated metabolic abnormalities. Recent studies have highlighted the role of dysfunctional adipose progenitor cells (APCs) in WAT fibrosis and impaired adaptive tissue plasticity, leading to systemic insulin resistance. However, therapeutic options for WAT fibrosis are limited. Intermittent fasting (IF) is an effective dietary regimen for weight control and metabolic improvement through various mechanisms. Here, we show that IF confers therapeutic benefits in obese mice through reduction of WAT fibrosis. Single-cell analyses revealed that IF significantly reduces fibrotic signatures within APCs along with upregulation of circadian pathways. Importantly, adipose progenitor cell-specific Bmal1 deficiency was associated with increased fibrotic signatures in WAT. Complementary experiments in the broader study further demonstrated that Bmal1 deficiency impaired the beneficial effects of IF, supporting an important role for APC circadian regulation in IF-induced adipose tissue remodeling. Collectively, our findings highlight the novel role of the APC circadian rhythm in plasticity of WAT and the metabolic response to IF.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE342153 | GEO | 2026/08/31

REPOSITORIES: GEO

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