Abstract
New treatments are urgently needed to address the current epidemic of obesity and diabetes. Recent studies have highlighted multiple pathways whereby serotonin (5-HT) modulates energy homeostasis, leading to a renewed interest in the identification of 5-HT-based therapies for metabolic disease. This review aims to synthesize pharmacological and genetic studies that have found diverse functions of both central and peripheral 5-HT in the control of food intake, thermogenesis, and glucose and lipid metabolism. We also discuss the potential benefits of targeting the 5-HT system to combat metabolic disease.
Highlights
A rich history of research connects serotonin (5-HT) signaling with food intake, energy expenditure, hormone balance and nutrient metabolism
Due to the growing public health crisis of obesity and diabetes, the role of 5-HT in metabolic homeostasis has recently led to a renewed interest in 5-HT pathways as novel therapeutic targets in the treatment of metabolic disease. 5-HT is synthesized from dietary l-tryptophan in a two-step enzymatic reaction involving tryptophan hydroxylases (TPHs) and l-amino acid decarboxylase (AADC; Walther and Bader, 2003)
5-HT serves as a secreted hormone produced in intestinal enterochromaffin cells, enteric neurons, pancreatic cells, and adipose tissue (Berger et al, 2009)
Summary
New treatments are urgently needed to address the current epidemic of obesity and diabetes. Recent studies have highlighted multiple pathways whereby serotonin (5-HT) modulates energy homeostasis, leading to a renewed interest in the identification of 5-HT-based therapies for metabolic disease. This review aims to synthesize pharmacological and genetic studies that have found diverse functions of both central and peripheral 5-HT in the control of food intake, thermogenesis, and glucose and lipid metabolism. We discuss the potential benefits of targeting the 5-HT system to combat metabolic disease.
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