Novel nutrient based approaches for appetite regulation and obesity

Obesity is a global epidemic, with 1 in 8 people being affected and facing greater risks of morbidity and mortality. Increased protein intake in the daily diet has been shown to contribute to appetite management and thus has the potential to help prevent obesity. These benefits have contributed to the increasing protein consumption observed globally over the past few decades. Plant-based proteins may serve as a more environmentally sustainable alternative to animal-derived proteins; however, research on the appetite regulatory effects of plant-based proteins is still in its early stages.

This thesis therefore focused on assessing the effects of plant and animal-derived proteins (potato, PP; rice, RP; pea, PeP and whey, WP) in the context of appetite regulation and obesity, developing and utilising novel cell-based models employing the Caco-2 and STC-1 cell lines to assess the mechanisms underlying the whole-body effects observed in complementary human studies. The study is the first to demonstrate gastric inhibitory peptide (GIP) expression and secretion in the Caco-2 cell line, while observing significantly higher GIP, glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY) secretion with RP treatment vs all other conditions at 6.25 mg/mL protein digestate exposure following four hours of treatment. Appetite hormone secretion with PP treatment (6.25 mg/mL) was also significantly higher vs WP. However, treatment with lower protein concentration (4.17 mg/mL) for the same duration led to significantly higher GLP-1 and PPY secretion with PP vs RP, with no increases observed with RP. Identical trends were observed in both Caco-2 and STC-1 cells.

Additionally, for the first time WP was observed to lead to significantly higher postprandial plasma GIP levels compared to PP at 30 min (22.67 ± 10.73 pg/mL, p = 0.0159), 60 min (18.85 ± 9.69 pg/mL, p = 0.0041) and 120 min (15.33 ± 6.16 pg/mL, p = 0.0012) when consumed as part of a mixed macronutrient meal, resulting in insulin-independent glycaemic responses in healthy male participants (n = 10, mean age 28.4 years). Circulatory GLP-1 levels were significantly higher with both WP and PP vs control, with mean differences of 27.42 pmol/L (± 9.31, p = 0.0315) and 27.05 pmol/L (± 8.53, p = 0.0178), respectively, 180 min following meal consumption.

Taken together, the results demonstrate that differences in concentration, digestion rate, as well as the levels of available amino acid (AA) and bioactive peptides with potential appetite-suppressive effects (e.g. potato protease 2) or calcium-binding and -chelating characteristics (e.g. peptide AHV) present in the digested fractions of proteins may have influenced the observed appetite regulatory effects in vitro in either cell line. These data highlight the suitability of Caco-2 cells as an alternative cell line model for nutrient-induced appetite hormone regulatory studies. The metabolic responses evoked by WP as part of a mixed meal indicate that it may elicit potential benefits for populations where tighter control of glycaemic and insulinemic regulation is required, while the effects of plant-based PP on GLP-1 secretion indicate that it could be as effective for appetite regulation as WP, when combined with an appropriate carrier. This study thus provides novel insights on the relative appetite regulatory effects of dietary proteins both in vitro and in vivo and paves the way for further investigation into developing non-pharmacological approaches to managing obesity.