Obesity is an epidemic with enormous health, economic and social burdens. Current drugs for obesity treatment are far from ideal in terms of efficacy and side effects. Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments. Some of these receptors also cause monogenic obesity in humans. Subject matter: obesity is an epidemic and G protein-coupled receptors are promising drug targets, with significant potential as new anti-obesity drugs Chapters are written by leading experts

Obesity is one of the relevant public health concerns and it is evident that body weight control is achieved through highly integrated physiological interactions like nutrient selection. Presenting an account of the roles of specific peptides in energy balance, this title provides an understanding of the patho-physiology of energy balance.

Energy homeostasis is a dynamic and complex process that maintains a balance between energy intake and expenditure. G protein coupled receptors (GPCRs), the largest family of transmembrane receptors, are critical for the cellular communication needed to coordinate processes involved in energy homeostasis (e.g. food intake). Indeed, metabolites are thought to act as sensors of energy stores by activating GPCRs in order to regulate energy homeostasis. Amino acids in particular have been shown to activate a growing number of GPCRs such as the calcium receptor (CaR), the orphan GPCRs GPR142 and GPR139, the purinergic receptor P2Y, and the hydroxycarboxylic acid receptor HCA3. This study aimed to further elucidate the role of monomeric amino acids as signaling molecules by employing a high throughput screen approach in which 19 monomeric amino acids were screened against 72 lipid metabolism GPCRs in a human cell line. Receptor activity was measured using the G-protein independent ?-arrestin recruitment PRESTO TANGO assay. It was found that a mixture of 19 essential and non-essential amino acids significantly activated 14 lipid metabolism GPCRs. Of these, MC4, DP2, GPBA, S1P1, and S1P4 were chosen for further investigation and were found to be significantly activated by 0.8 mM L-Phenylalanine. This finding suggests L-Phenylalanine may play a more prominent role as a signalling molecule at GPCRs regulating energy homeostasis than previously thought. This aids in elucidating the satiating mechanisms of high protein diets and has important implications for research into diseases such as obesity, type 2 diabetes, and the metabolic syndrome.

Latest research on Adhesion GPCRs has unearthed surprising revelations about the events that govern the signal transduction of these receptor molecules and the cellular and organ requirements for these signals. Unexpected and unprecedented findings suggest that Adhesion GPCRs constitute a group of receptors that sense mechanical stimuli and transcode them into metabotropic signals through the action of a novel activation paradigm. Interdisciplinary efforts transcending many areas of biomedical research including pharmacology, physiology, genetics, cell biology, structural biology, biochemistry and bioinformatics were necessary to unveil these fundamental properties. The scientific leaders in the field that carried this research effort have teamed up here to provide a comprehensive overview of our current understanding, how Adhesion GPCRs signal and how these receptors shape organ structure and function.