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.

Keywords: appetite; cholecystokinin; dietary studies; glucagon-like peptide-1; infusion studies; peptide YY; satiety.

Figure 1

Food intake induces an increase in circulating gastrointestinal peptides CCK, GLP-1 and PYY, as well as parallel increase in satiation and satiety. However, whether these ‘satiety’ peptides in turn elicit a direct physiological effect on aspects of eating behaviour is less well-understood.

Figure 2

Flow diagram of article selection for (a) DIET and (b) INFUSION studies. Some articles reported >1 GI-peptide.

Figure 3

Boxplots showing the (a) baseline concentration, (b) C_max, peak concentration, and (c) fold change of CCK between DIET (N = 620, K = 39) and INFUSION (N = 98, K = 8). The weighted means were significantly different between DIET and INFUSION for all (p < 0.01, all).

Figure 4

Boxplots showing the (a) baseline concentration, and (b) C_max, peak concentration of total GLP-1 between DIET (N = 479, K = 37) and INFUSION (N = 67, K = 6). The weighted means were significantly different between DIET and INFUSION for all (p < 0.01, all).

Figure 5

Boxplots showing the (a) baseline concentration, and (b) C_max, peak concentration of active GLP-1 between DIET (N = 683, K = 29) and INFUSION (N = 81, K = 5). The weighted means were significantly different between DIET and INFUSION for (a) baseline concentration (p < 0.01), but not (b) C_max, peak concentration (p = 0.96).

Figure 6

Boxplots showing fold change of GLP-1 (total and active) between DIET (N = 1162, K = 66) and INFUSION (N = 152, K = 11). The weighted means were significantly different between DIET and INFUSION (p < 0.01).

Figure 7

Boxplots showing (a) baseline concentration, (b) C_max, peak concentration, and (c) fold change of PYY between DIET (N = 804, K = 50) and INFUSION (N = 132, K = 15). The weighted means were significantly different between DIET and INFUSION for all (p < 0.01, all).