.-Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320 -425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time-or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation. appetite; insulin ALTHOUGH MEALTIME HUNGER IS a common, daily experience, the nature of the molecular determinants underlying this sensation is debated. Ghrelin is a recently discovered enteric peptide hormone that is the only known circulating orexigen and one of very few substances shown to stimulate appetite and food intake when administered to humans (22,36,46,51). Orexigenic actions of ghrelin have been demonstrated after modestdose peripheral injections that generate approximately physiological blood levels in humans and rodents, suggesting that normal fluctuations in endogenous circulating ghrelin can affect appetite (51, 52). Considerable evidence in multiple species implicates ghrelin in the control of preprandial hunger and meal initiation. Additional evidence suggests that ghrelin may also participate in long-term body-weight regulation, and blockade of ghrelin signaling is actively being explored as a potential anti-obesity modality (13, 14).The following observations are consistent with the hypothesis that ghrelin contributes to preprandial hunger and meal initiation (12,14). 1) The greatest amount of ghrelin is produced by the stomach and duodenum, organs that are well positioned to sense the presence or absence of recently ingested food (3,16,19,22,24). 2) As predicted for a meal initiator, ghrelin levels incre...

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Snacking is often presumed to contribute to obesity, but to date, studies have not demonstrated such a causal relationship, probably because a clear definition of snacking is still elusive. The usual one, i.e. any intake between traditional meals, has no physiological basis. Moreover, because some evidence suggests that frequent meals may prevent overweight, any confusion between snacks and meals may mask the deleterious effect of snacks on energy balance. Therefore, we developed a biobehavioral approach to assess whether objective criteria for eating a meal and snacking could be determined. Our main findings were that regardless of the time of consumption or macronutrient composition, snacks exerted a weak satiety effect, with those higher in protein having the strongest. The energy content of snacks was never compensated for at the next meal and led consistently to a positive energy balance compared with no-snack conditions. Biologically, the snack-induced insulin secretion suppressed the late increase in plasma FFA, which may have contributed to the inhibition of satiety. Lastly, snacking was not preceded by the glucose and insulin profile observed prior to a spontaneously requested meal. In conclusion, further studies on the role of snacking in energy balance should include criteria other than nutrient composition or consumption between meals for defining these eating occasions as snacks.

CHAPELOT, DIDIER, CORINNE MARMONIER, ROBERTE AUBERT, CHLOÉ ALLÈ GRE, NICOLAS GAUSSERES, MARC FANTINO, AND JEANINE LOUIS-SYLVESTRE. Consequence of omitting or adding a meal in man on body composition, food intake, and metabolism. Obesity. 2006;14:215-227. Objective: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal. Research Methods and Procedures: Twenty-four young normal-weight male subjects were recruited, 12 usual fourmeal and 12 usual three-meal eaters, differing only in the consumption of an afternoon meal. They omitted or added a fourth meal during a 28-day habituation period and were asked to report their intake on three 3-day occasions. Before and after this habituation period, subjects participated in a session with a time-blinded procedure, and blood was collected continuously from lunch to the spontaneously requested dinner. Body composition, respiratory quotient, and biochemical parameters were measured in the late evening preceding each session. Results: Omitting a meal was followed by increases in fat mass (360 Ϯ 115 grams, p Ͻ 0.05), late evening leptin concentration (20.7 Ϯ 11.0%, p Ͻ 0.05), and respiratory quotient (3.7 Ϯ 1.4%, p Ͻ 0.05). Increase in the percentage of dietary fat during the habituation period (ϩ4.1 Ϯ 2.0%, p Ͻ 0.05) was correlated with fat mass (r ϭ 0.66, p Ͻ 0.05). Adding a meal had no effect, but, in both groups, the change in energy content at this fourth eating occasion was correlated with the change in adiposity. Discussion: Our results suggest that adiposity may increase when young lean male subjects switch from a four-to a three-meal pattern by removing their usual afternoon meal. This effect could be partly mediated by a change in the macronutrient composition of the diet.