A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans

Abstract

The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene-related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values (r ‫؍‬ 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age (r ‫؍‬ 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans.

Anticipatory physiological regulation in feeding biology: Cephalic phase responses

“…Leptin concentration gradually rose throughout the day, with small declines immediately after each meal, and reached a zenith roughly during the middle of the sleep period. Ghrelin followed the same pattern (Figure 8), except for the pronounced surges immediately prior to a meal, followed by equally dramatic declines immediately after the meal (Cummings et al, 2001). Because the meals were provided at known, fixed times, this evidence supports the hypothesis that the surge in ghrelin secretion prior to meals is a cephalic phase response that serves to initiate feeding and/or to prepare the person to digest and metabolize food.…”

“…In human volunteers provided meals on a fixed schedule, plasma ghrelin concentration displayed a consistent pattern of being low immediately after a meal, slowly increasing, and then having a rapid increase in concentration immediately prior to the next meal (Cummings et al, 2001; Figure 7). The pattern of ghrelin concentration was roughly opposite to the pattern of insulin concentration, but in phase with the circadian cycle of leptin concentration, though much more variable than leptin concentration.…”

“…Indeed, ghrelin is as potent at stimulating feeding as neuropeptide Y. Starvation increases ghrelin plasma concentration and refeeding rapidly decreases circulating ghrelin (Ariyasu et al, 2001). Ghrelin has been suggested to act to initiate feeding (Cummings et al, 2001). …”

“…Subjects were aware of when meals were to be provided and the time. Data from Cummings et al (2001).…”

Evaluation and Diagnostic Potential of Serum Ghrelin in Feline Hypersomatotropism and Diabetes Mellitus

“…For instance, ghrelin is known to be influenced by meals in man 26. Nevertheless, on 24‐hour serial assessment of circulating ghrelin concentrations in humans, it was shown that samples taken before breakfast correlated strongly with 24‐hour integrated area under the curve values ( r  = 0.873), suggesting that a single starved morning sample could be used as a surrogate for 24‐hour profiles to estimate overall ghrelin concentrations 27. Therefore, to minimize the effects of daily ghrelin dynamics in this study, all cat samples were taken in the early morning and before food.…”