Kim Dong Hee, Lee Min Jin, Kang Dasol, Khang Ah Reum, Bae Ji Hyun, Kim Joo Yeon, Kim Su Hyun, Kang Yang Ho, Yi Dongwon
Department of BIT Fusion Technology Center, Pusan National University, Busan 46241, Republic of Korea.
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
Curr Issues Mol Biol. 2024 Jul 15;46(7):7505-7515. doi: 10.3390/cimb46070445.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 μL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide () and pro-opiomelanocortin () in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates and gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of and . These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂通过抑制肾脏对葡萄糖的重吸收来调节2型糖尿病（T2DM）患者的血糖水平。本研究调查了SGLT2抑制剂恩格列净（EMPA）对下丘脑能量调节的影响。为了直接研究SGLT2抑制剂在下丘脑中的作用，我们通过脑室内（i.c.v.）注射将EMPA注入小鼠脑室。在将i.c.v.套管用牙科粘固剂固定在颅骨上后，让小鼠恢复5天，然后再接受载体或EMPA（50 nM/2 μL）注射。在高脂饮食（HFD）诱导的肥胖模型中，我们测定了下丘脑中刺鼠相关肽（）和阿黑皮素原（）的基因表达水平。此外，我们评估了FoxO1的表达，它调节下丘脑细胞系中的 和 基因转录。我们发现，EMPA直接影响了对能量稳态至关重要的POMC和AgRP内源性mRNA的表达，并在高脂饮食诱导的肥胖小鼠中调节了它们的转录。此外，EMPA影响了葡萄糖稳态的关键转录调节因子FoxO1的表达，从而调节了 和 的转录活性。这些结果表明，EMPA显著影响下丘脑能量稳态，突出了其作为肥胖和T2DM管理调节剂的潜力。
