Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes.
Dong Hee KimMin Jin LeeDasol KangAh Reum KhangJi Hyun BaeJoo Yeon KimSu Hyun KimYang Ho KangDongwon YiPublished in: Current issues in molecular biology (2024)
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 ( AgRP ) and pro-opiomelanocortin ( POMC ) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC 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 POMC and AgRP . These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.
Keyphrases
- high fat diet induced
- insulin resistance
- transcription factor
- high fat diet
- gene expression
- poor prognosis
- genome wide identification
- metabolic syndrome
- adipose tissue
- signaling pathway
- skeletal muscle
- type diabetes
- binding protein
- blood glucose
- genome wide
- weight loss
- long non coding rna
- dna methylation
- glycemic control
- oxidative stress
- pi k akt
- copy number
- weight gain
- oral health
- extracorporeal membrane oxygenation
- diabetic rats
- physical activity
- obstructive sleep apnea
- high glucose
- blood pressure
- high resolution
- platelet rich plasma
- intensive care unit
- respiratory failure
- anti inflammatory
- genome wide analysis