Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

摘要: Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is rate-limiting enzyme mitochondrial fatty acid β-oxidation it been proposed mediator fasting ghrelin orexigenic signalling. However, relationship between changes CPT1A activity intracellular downstream effectors VMH that contribute to appetite modulation not fully understood. To this end, we examined effect long-term expression permanently activated isoform by using an adeno-associated viral vector injected into rats. Peripherally, procedure provoked hyperghrelinemia hyperphagia, which led overweight, hyperglycemia insulin resistance. In mediobasal (MBH), CPT1AM did modify acyl-CoA or malonyl-CoA levels. altered MBH lipidomic profile since ceramides sphingolipids increased phospholipids decreased. Furthermore, detected vesicular γ-aminobutyric transporter (VGAT) reduced glutamate 2 (VGLUT2) expressions, both transporters involved signal. Taken together, these observations indicate contributes modulating neurotransmitter lipid components influence pathways VMH.