How Satiating Are the ‘Satiety’ Peptides: A Problem of Pharmacology versus Physiology in the Development of Novel Foods for Regulation of Food Intake

Abstract

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop ‘functional’ foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or ‘satiety’ peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating ‘thresholds’ of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin ‘satiety’ peptides for weight loss remains a significant challenge.

New Zealand Bitter Hops Extract Reduces Hunger During a 24 h Water Only Fast

“…These data suggest that the magnitude of hunger changes observed here could be explained by the actions of anorexigenic GI peptide secretion, and provides support for the conclusion that these hormones are likely mediators of the altered appetite ratings. However, as the relationship between anorexigenic gut peptides and appetite is complicated [71], we cannot preclude other mechanisms contributing to the observed effects, and it is possible that bitter compound regulation of intestinal motility and gastric accommodation may have contributed to the reported bioactivity [41,72].…”

Appetite, the enteroendocrine system, gastrointestinal disease and obesity

“…Human dietary preload studies yield variable results when measuring the association between post-prandial changes in circulating levels of these gut peptides and subsequent changes in appetite and satiety (15–21) . Those reporting a correlation between increased plasma satiety hormone levels and post-prandial suppression of appetite, or increased satiety, do not provide sufficient evidence to conclude a causal link with increasing circulating peptides actually driving appetite-related behaviours (22) .…”

“…The majority of peptide infusion studies, however, do report significant effects in appetite outcomes, frequently in a dose-dependent manner (31–34) . The difficulty when extrapolating these data in order to draw conclusions regarding the role of satiety hormones in appetite regulation in healthy human subjects is that the majority of infusion studies result in a rapid increase of the relevant gut peptide, reaching supra-physiological plasma concentrations (22,35) .…”

“…In a recent carefully crafted review, Lim and Poppitt compared fold changes from baseline in gut hormone concentrations between dietary preload studies and peptide infusion studies (22) . The relationship between peptide concentrations and appetite behaviours in both groups were also explored.…”

“…Furthermore, any increase in gut peptides reported in the dietary preload studies was not consistent with appetite outcomes. Taken together, the authors concluded that it is very difficult to reach these threshold changes in gut peptides through dietary manipulation alone and thus the role of endogenously released satiety hormones in appetite regulation following a meal remains unclear (22) .…”