Ceramide regulated intracellular FGF13 impairs adipose nutrient sensing and glucose metabolism
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ABSTRACT:
PROVIDER: PRJNA790647 | ENA |
REPOSITORIES: ENA
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Project description:Although, ectopic ceramide accumulation impairs nutrient sensing in adipocytes, leading to deterioration in energy and glucose homeostasis, the underlying mechanisms remain poorly defined. Using, comparative screen to identify ceramide regulated effector molecule in adipose tissue, we found fibroblast growth factor 13 (FGF13) as one of the critical ceramide-effector molecules that impair nutrient sensing in adipocytes. FGF13 is a cytosolic, non-secreted FGF belonging to a non-canonical FGF family member that comprises of FGF11-FGF14 and do not activate FGF receptors. FGF13 has been implicated in numerous physiological process such as development, cardiac arrythmias, neurological disease and cancer. We demonstrate that FGF13 expression is highly induced in adipose tissue in response to a high fat diet, and its expression is negated by pharmacological and genetic interventions that inhibit ceramide biosynthesis. Inhibition of FGF13 in adipocytes (white, brown and beige), alters adipocyte morphology, prevents the development of obesity, improves glucose homeostasis, insulin sensitivity and resolves hepatic steatosis
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