Kiss1-FASN participates fatty acid synthesis via high-fat diet in PgVAT of female mice

Long-term consumption of high-fat diet (HFD) leads to energy surplus, resulting in excessive adipose tissue (AT) accumulation and dysfunction. Kiss1 is known to play a role in the metabolic regulation of AT. To explore the involvement of Kiss1 in mediating the effects of energy surplus induced by HFD, we conducted an 8-week intervention combining aerobic exercise and HFD in mice with AT-specific knockout (KO) and overexpression of Kiss1, along with HFD treatment in Kiss1-KO 3T3-L1 cells. Our results revealed that in perigonadal visceral AT (PgVAT) of female mice, the expression of Kiss1 and FASN is positively correlated. In addition, Kiss1 participate the fatty acid (FA) synthesis pathway in PgVAT of female mice. When we overexpressed Kiss1 in ATs of female mice, we found that aerobic exercise reduced FASN levels by downregulating Kiss1 expression in PgVAT, thereby may suppressing the FA synthesis capacity. This study provides novel insights for developing targeted therapeutic strategies against obesity and associated metabolic disorders.