Current trends in targeting the hormonal regulation of appetite and energy balance to treat obesity

Abstract

With the eruption of the obesity pandemic over the past few decades, much research has been devoted to understanding the molecular mechanisms by which the human body regulates energy balance. These studies have revealed several mediators, including gut/pancreatic/adipose hormones and neuropeptides that control both short- and long-term energy balance by regulating appetite and/or metabolism. These endogenous mediators of energy balance have been the focus of many anti-obesity drug-development programs aimed at either amplifying endogenous anorexigenic/lipolytic signaling or blocking endogenous orexigenic/lipogenic signaling. Here, we discuss the efficacy and safety of targeting these pathways for the pharmacologic treatment of obesity.

Keywords::

• appetite
• energy balance
• gut–neural axis
• obesity
• pharmacotherapeutics
• satiety

Financial & competing interests disclosure

Support was provided by NIH grants R01 CA75123, R01 CA95026, RC1 CA75123 and P30 CA56036, and from Targeted Diagnostic and Therapeutics, Inc (SAW). Michael A Valentino is the recipient of a predoctoral fellowship from the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation. Francheska Colon-Gonzalez is the recipient of a post-doctoral fellowship from the PhRMA Foundation. Scott A Waldman is the Samuel MV Hamilton Endowed Professor and is a consultant to Merck and CombiMab, Inc., the Chair of the Data Safety Monitoring Board for the C-Cure TrialÔ sponsored by Cardio3 Biosciences and the Chair (uncompensated) of the Scientific Advisory Board to Targeted Diagnostics and Therapeutics, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.