Knowing the biological signals associated with appetite control is crucial for understanding the regulation of food intake. Biomarkers of appetite have been defined as physiological measures that relate to subjective appetite ratings, measured food intake, or both. Several metabolites including amino acids, lipids and glucose were proposed as key molecules associated with appetite control over 60 years ago, and along with bile acids are all among possible appetite biomarker candidates. Additional metabolites that have been associated with appetite include endocannabinoids, lactate, cortisol and β-hydroxybutyrate. However, although appetite is a complex integrative process, studies often investigated a limited number of markers in isolation. Metabolomics involves the study of small molecules or metabolites present in biological samples such as urine or blood, and may present a powerful approach to further the understanding of appetite control. Using multiple analytical techniques allows the characterisation of molecules, such as carbohydrates, lipids, amino acids, bile acids and fatty acids. Metabolomics has proven successful in identifying markers of consumption of certain foods and biomarkers implicated in several diseases. However, it has been underexploited in appetite control or obesity. The aim of the present narrative review is to: (1) provide an overview of existing metabolites that have been identified in human biofluids and associated with appetite control; and (2) discuss the potential of metabolomics to deepen understanding of appetite control in humans.

Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0·0209) and docosahexaenoylethanolamide (DHEA) levels (P=0·0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub-population that appears to benefit from increased consumption of DHA and oleic acid.

The CB1 cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant; SR141716A), and oleoylethanolamide (OEA) are known to reduce food consumption, by, at least partially, a peripheral regulation of feeding. The effects of systemic SR141716A or OEA (5 mg/kg) administrations on food consumption in 24 h food-deprived and fed rats were investigated. In fasted rats, SR141716A and OEA produced an inhibition in food intake measurable the first 20 min following injection. The increase in ghrelin levels observed in the vehicle-injected rats was abolished in animals receiving OEA and significantly reduced with SR141716A. Neither OEA nor SR141716A modified glucagon-like peptide-1 (7–36) amide portal levels 20 min after the administration. In fed rats, plasma ghrelin levels of SR141716A- and OEA-treated rats were 35% lower as compared with those of the vehicle-injected rats. These results show an influence of cannabinoid agents on circulating ghrelin levels and suggest that their short-term action on appetite seems to be in accordance with the control of secretion of gastrointestinal orexigenic peptides, mainly expressed in the upper part of the gastrointestinal tract.