Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance, Incretin Secretion and Appetite in Humans.

BACKGROUND: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. METHODS: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At -30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. RESULTS: PNO-FFA augmented GLP-1 secretion from 0-360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240-360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). CONCLUSIONS: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.

Acute effects of delayed-release hydrolyzed pine nut oil on glucose tolerance, incretins, ghrelin and appetite in healthy humans.

BACGROUND & AIM: 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. METHODS: In two cross-over studies, we evaluated 3 g unhydrolyzed pine nut oil (PNO-TG) or 3 g PNO-FFA versus no oil in eight healthy, non-obese subjects (study 1), and 3 g PNO-FFA or 6 g PNO-FFA versus no oil in ten healthy, overweight/obese subjects (study 2) in both studies given in delayed-release capsules 30 min 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. RESULTS: Both 3 g PNO-FFA in study 1 and 6 g PNO-FFA in study 2 markedly increased GLP-1 levels (p < 0.001) and attenuated ghrelin levels (p < 0.001) during the last 2 h 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 2 h of the OGTT. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRY NUMBERS: NCT03062592 and NCT03305367.

Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice.

Mutations in Hes1, a target gene of the Notch signalling pathway, lead to ectopic pancreas by a poorly described mechanism. Here, we use genetic inactivation of Hes1 combined with lineage tracing and live imaging to reveal an endodermal requirement for Hes1, and show that ectopic pancreas tissue is derived from the dorsal pancreas primordium. RNA-seq analysis of sorted E10.5 Hes1+/+ and Hes1-/- Pdx1-GFP+ cells suggested that upregulation of endocrine lineage genes in Hes1-/- embryos was the major defect and, accordingly, early pancreas morphogenesis was normalized, and the ectopic pancreas phenotype suppressed, in Hes1-/-Neurog3-/- embryos. In Mib1 mutants, we found a near total depletion of dorsal progenitors, which was replaced by an anterior Gcg+ extension. Together, our results demonstrate that aberrant morphogenesis is the cause of ectopic pancreas and that a part of the endocrine differentiation program is mechanistically involved in the dysgenesis. Our results suggest that the ratio of endocrine lineage to progenitor cells is important for morphogenesis and that a strong endocrinogenic phenotype without complete progenitor depletion, as seen in Hes1 mutants, provokes an extreme dysgenesis that causes ectopic pancreas.