Ghrelin in obesity.
Ghrelin was discovered for its ability to bind the growth hormone secretagogue receptor (GHSR1a) and stimulate growth hormone release. However, much research conducted with this novel stomach hormone is focused on proposed roles for it to participate in regulating energy balance. Exogenous administration of ghrelin stimulates food consumption in experimental animals and humans, presenting the hormone as the first to stimulate appetite after peripheral administration and implicates it for an etiology of obesity. The hormone also presents other exceptional characteristics that solicit need for future study. The peptide is modified by acylation with a mediumchain fatty acid on its third residue, and it is that ghrelin peptide that binds GHS-R1a. Enzymes or transfer proteins responsible for such acylation and de-acylation remain unknown. Specific assays for both acyl- and des-acyl ghrelin are not available nor are methods to prevent de-acylation in blood samples. Such knowledge is important because des-acyl ghrelin is reported to bestow biology distinct from that of ghrelin and that signal may actually oppose those prescribed for its acylated parent. This review of ghrelin data relating to obesity recognizes the complexity of ghrelin endocrinology and attempts to be cautious when discussing studies that measured ghrelin during different physiological states. Although much more exploration is needed, we placed more emphasis on reviewing studies during different physiological states when conclusions are less dependent on measurement of ghrelin. Despite these shortcomings, we conclude that there is ample evidence indicating ghrelin participates in regulating energy balance.
Heiman
Mark L
ML
Lilly Research Laboratories, ADivision of Eli Lilly and Co., Lilly Corporate Center, Indianapolis, Indiana.
Witcher
Derrick R
DR