Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月3日

查看全文
  • Weiwei Yuan,
  • Shengqing He,
  • Yuan Zang,
  • Liping Deng

摘要

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.