Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues

Abstract

.-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...

The role of the central ghrelin system in reward from food and chemical drugs

“…Ghrelin levels increase pre-prandially (Cummings et al 2001) and have been shown to correlate with hunger scores in healthy subjects (Cummings et al 2004) indicating that, at least in normal physiology, acute changes of ghrelin may have a role in the decision to eat and/or serve as a circulating hunger hormone. Studies in rodents exploring the precise parenchymal targets for ghrelin's orexigenic effects have identified a number of candidate sites: orexigenic responses have been observed when injected into discrete brain areas that include the hypothalamus (arcuate nucleus, ventromedial nucleus, dorsomedial nucleus, paraventricular nucleus, lateral hypothalamus) (Olszewski et al 2003a;Olszewski et al 2003b;, the nucleus tractus solitarius of the brainstem (Faulconbridge et al 2003), the central nucleus of the amygdala (Olszewski et al 2003) and mesolimbic reward areas (the ventral tegmental area (VTA) and nucleus accumbens (N.Acc) Naleid et al 2005).…”

“…For a review on this topic, we refer the reader to Skibicka and Dickson 2011. In normal weight healthy volunteers, ghrelin has been shown to increase hunger scores, to enhance food palatability and to increase caloric intake in a free-feeding buffet situation (Cummings et al 2004;Druce et al 2006;. One recent study of food economics reported that ghrelin even increases the amount of money an individual is prepared to pay for individual food items (Tang et al 2011).…”

Intense sweeteners, energy intake and the control of body weight

“…Only Louis-Sylvestre (Himaya et al, 1997) used the meal demand paradigm to measure the impact of preloads on satiety. Those data were later linked to the participants' ghrelin levels, providing a valuable link between data from the behavioral preload paradigm and plasma levels of hunger and satiety hormones (Cummings et al, 2004).…”

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

“…Due to lack of normative data on obestatin in humans when the study was performed, subject numbers were based on recruitment and the minimum numbers needed in previous published work on ghrelin profiles in humans. 18 Obesity was defined as BMI430 kg/m 2 according to the criteria of the World Health Organisation and the International Obesity Task Force. All gastrectomy subjects underwent total gastrectomy for gastric carcinoma at least 12 months previously and were in remission (all had no evidence of recurrence by gastroscopy within the last 12 months).…”