Fig. 8
From: Regulation of feeding and metabolism by fat mass and obesity-associated protein in zebrafish
Scheme summarizing aspects of zebrafish feeding and metabolism modulated when FTO was inhibited with rhein. It suppresses orexigenic mediators including NPY and orexin, while enhancing satiety-related signals including POMC, CART, IRX3, and MC4R, thereby reducing food intake. In hepatic tissue or hepatocytes, rhein downregulates gluconeogenic genes (G6PC, PCK1, ATF4), resulting in decreased glucose production. Concurrently, activation of AMPK promotes phosphorylation of ACC, alleviates CPT1 inhibition, and enhances Ī²-oxidation, with PPARĪ± and its downstream targets (CPT1A, ACOX1), further supporting fatty acid catabolism. Lipogenic processes are attenuated through suppression of SREBF1 and its downstream effectors (FAS, SCD), together with downregulation of CREB. Collectively, these findings suggest that inhibition of FTO by rhein may contribute to improved metabolic homeostasis by shifting cellular energy metabolism away from gluconeogenesis and lipid synthesis toward oxidative and catabolic pathways. Acronyms used and their full forms: Proopiomelanocortin (POMC), amphetamine-regulated transcript (CART), agouti-related melanocortin 4 receptor (MC4R) Iroquois homeobox protein (IRX3), proliferator-activated receptor alpha (PPARĪ±) and AMPāactivated protein kinase (AMPKĪ±). Sterol regulatory element binding transcription factor 1 (SREBF1), cAMP Response Element-Binding protein (CREB) stearoyl-CoA desaturase (SCD), carnitine palmitoyltransferase I (CPT-1), Fatty acid synthase (FAS), Activating transcription factor 4 (ATF4), Glucose-6-phosphatase (G6PC), phosphoenolpyruvate carboxykinase 1(PCK1).
