Abstract

Pinolenic acid, a major component (~20%) of pine nut oil, is a dual agonist of the free fatty acid receptors, FFA1 and FFA4, which may regulate release of incretins and ghrelin from the gut. Here, we investigated the acute effects of hydrolyzed pine nut oil (PNO-FFA), delivered to the small intestine by delayed-release capsules, on glucose tolerance, insulin, incretin and ghrelin secretion, and appetite. In two cross-over studies, we evaluated 3g unhydrolyzed pine nut oil (PNO-TG) or 3g PNO-FFA versus no oil in eight healthy, non-obese subjects (study 1), and 3g PNO-FFA or 6g PNO-FFA versus no oil in ten healthy, overweight/obese subjects (study 2) in both studies given in delayed-release capsules 30min prior to a 4-h-oral glucose tolerance test (OGTT). Outcomes were circulating levels of glucose, insulin, GLP-1, GIP, ghrelin, appetite and gastrointestinal tolerability during OGTT. Both 3g PNO-FFA in study 1 and 6g PNO-FFA in study 2 markedly increased GLP-1 levels (p<0.001) and attenuated ghrelin levels (p<0.001) during the last 2h of the OGTT compared with no oil. In study 2, these effects of PNO-FFA were accompanied by an increased satiety and fullness (p<0.03), and decreased prospective food consumption (p<0.05). PNO-FFA caused only small reductions in glucose and insulin levels during the first 2h of the OGTT. Our results provide evidence that PNO-FFA delivered to the small intestine by delayed-release capsules may reduce appetite by augmenting GLP-1 release and attenuating ghrelin secretion in the late postprandial state. NCT03062592 and NCT03305367.

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