Glibenclamide restores dopaminergic reward circuitry in obese mice through interscauplar brown adipose tissue

Yi Ying Kuo, Jie Kuan Lin, Ya Tin Lin, Jin Chung Chen, Yu Ming Kuo, Po See Chen, Sheng Nan Wu, Pei Chun Chen

研究成果: Article同行評審

5 引文 斯高帕斯(Scopus)


Background: Obesity, a critical feature in metabolic disorders, is associated with medical depression. Recent evidence reveals that brown adipose tissue (BAT) activity may contribute to mood disorders, Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels regulate BAT sympathetic nerve activity. However, the mechanism through which BAT activity affects mood control remains unknown. We hypothesized the BAT is involved in depressive-like symptoms regulation by trafficking KATP channels. Methods: Eight-week-old male B6 mice fed with a high-fat diet (HFD) for 12 weeks exhibited characteristics of metabolic disorders, including hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as depressive symptoms. In this study, we surgically removed interscapular BAT in mice, and these mice exhibited immobility in the forced swim test and less preference for sugar water compared with other mice. To delineate the role of KATP channels in BAT activity regulation, we implanted a miniosmotic pump containing glibenclamide (GB), a KATP channel blocker, into the interscapular BAT of HFD-fed mice. Results: GB infusion improved glucose homeostasis, insulin sensitivity, and depressive-like symptoms. KATP channel expression was lower in HFD-fed mice than in chow-fed mice. Notably, GB infusion in HFD-fed mice restored KATP channel expression. Conclusion: KATP channels are functionally expressed in BAT, and inhibiting BAT-KATP channels improves metabolic syndromes and reduces depressive symptoms through beta-3-adrenergic receptor-mediated protein kinase A signaling.

出版狀態Published - 2020 8月

All Science Journal Classification (ASJC) codes

  • 內分泌學、糖尿病和代謝
  • 內分泌
  • 內分泌和自主系統
  • 精神病學和心理健康
  • 生物精神病學


深入研究「Glibenclamide restores dopaminergic reward circuitry in obese mice through interscauplar brown adipose tissue」主題。共同形成了獨特的指紋。