Sodium-glucose cotransporter 2 inhibitor ameliorates high fat diet-induced hypothalamic-pituitary-ovarian axis disorders.
Xiaolin ChenLili HuangLing CuiZhuoni XiaoXiaoxing XiongChen ChenPublished in: The Journal of physiology (2022)
High-fat diet (HFD) consumption is known to be associated with ovulatory disorders among women of reproductive age. Previous studies in animal models suggest that HFD-induced microglia activation contributes to hypothalamic inflammation. This causes the dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, leading to subfertility. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of lipid-soluble antidiabetic drugs that target primarily the early proximal tubules in kidney. Recent evidence revealed an additional expression site of SGLT2 in the central nervous system (CNS), indicating a promising role of SGLT2 inhibitors in the CNS. In type 2 diabetes patients and rodent models, SGLT2 inhibitors exhibit neuroprotective properties through reduction of oxidative stress, alleviation of cerebral atherosclerosis and suppression of microglia-induced neuroinflammation. Furthermore, clinical observations in patients with polycystic ovary syndrome (PCOS) demonstrated that SGLT2 inhibitors ameliorated patient anthropometric parameters, body composition and insulin resistance. Therefore, it is of importance to explore the central mechanism of SGLT2 inhibitors in the recovery of reproductive function in patients with PCOS and obesity. Here, we review the hypothalamic inflammatory mechanisms of HFD-induced microglial activation, with a focus on the clinical utility and possible mechanism of SGLT2 inhibitors in promoting reproductive fitness.
Keyphrases
- high fat diet
- insulin resistance
- body composition
- polycystic ovary syndrome
- oxidative stress
- high fat diet induced
- type diabetes
- diabetic rats
- adipose tissue
- end stage renal disease
- metabolic syndrome
- high glucose
- ejection fraction
- newly diagnosed
- skeletal muscle
- chronic kidney disease
- inflammatory response
- cardiovascular disease
- peritoneal dialysis
- drug induced
- prognostic factors
- physical activity
- poor prognosis
- traumatic brain injury
- neuropathic pain
- patient reported outcomes
- pregnant women
- weight gain
- endothelial cells
- spinal cord
- glycemic control
- lps induced
- cerebral ischemia
- subarachnoid hemorrhage
- fatty acid
- heat shock
- signaling pathway
- cerebrospinal fluid
- mouse model
- breast cancer risk