Adipocyte-specific NR5A2 deficiency ameliorates diet-induced metabolic syndrome by suppressing adipose tissue inflammation

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity is a global epidemic characterized by adipose tissue dysfunction, chronic inflammation, and metabolic syndrome. The orphan nuclear receptor NR5A2 has been implicated in metabolic regulation, but its role in adipocytes remains unclear. Here, we demonstrate that NR5A2 expression is upregulated in adipose tissue of high-fat diet (HFD)-fed and genetically obese (ob/ob) mice. Adipocyte-specific NR5A2 knockout (AKO) mice exhibited resistance to HFD-induced obesity, with reduced fat mass, smaller adipocytes, and improved glucose tolerance and insulin sensitivity. Mechanistically, NR5A2 ablation attenuated adipose tissue inflammation, evidenced by decreased pro-inflammatory cytokines (IL-6, TNF-α) and macrophage infiltration, while enhancing energy expenditure and thermogenesis. Additionally, AKO mice showed reduced hepatic steatosis and improved lipid profiles. In vitro, NR5A2 deficiency impaired adipocyte differentiation and lipid accumulation. These findings identify NR5A2 as a key regulator of adipocyte hypertrophy, inflammation, and systemic metabolism, suggesting its inhibition as a potential therapeutic strategy for obesity-related metabolic disorders.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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