FFAR Agonist on Incretins, Insulin, Lipids and Inflammation

NCT03062592 | Completed

• 1 other identifier: PINO2
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

Several free fatty acids receptors (FFARs) have been discovered. These have been implicated in metabolic processes and inflammation. Consequently, these receptors have attracted interest as targets for the treatment of metabolic and inflammatory diseases, including obesity and T2D. Two of these FFARs (FFAR1, FFAR4), which is activated by specific free fatty acids (FFAs), is expressed on enteroendocrine cells, pancreatic beta-cells and adipocytes. They have been linked to 1) increased GLP-1 secretion and hence the incretin-mediated increase in glucose-stimulated insulin secretion (GSIS) and suppression of glucagon secretion, 2) a direct positive effect on GSIS, 3) reduced inflammation and 4) improved insulin sensitivity. These functions and the abundance of fatty acids in food suggests that FFARs can be considered as nutrient sensing regulators of metabolism. Roux-en-Y gastric bypass (RYGB), frequently results in immediate beneficial effects on glucose metabolism and often complete remission of T2D. This may in part be explained by increased GLP-1 levels after surgery. It appears that the effect depends on nutrient delivery directly to the lower parts of the small intestine. It is possible that the RYGB effects are partly due to enteroendocrine stimulation of FFAR1 and perhaps FFAR4 by direct nutrient delivery, i.e. FFA release in the lower intestines. Pinolenic acid from pine nuts has been shown to be a potent dual FFAR1/FFAR4 agonist. Based on these findings the investigators have planned a number of human intervention studies in order to investigate 1) the optimal oral formulation of pine nut oil 2) whether it is possible to mimic the beneficial effects observed after RYGB, 2) if it is possible to increase meal-related GLP-1 secretion by stimulating FFAR1/FFAR4 on enteroendocrine cells causing improved GSIS and increased satiety and 3) enhancement of GSIS by directly stimulating FFAR1 (and perhaps FFAR4) on beta-cells.

Conditions

Type2 Diabetes Mellitus; Obesity

Keywords

incretin; insulin; glucose; appetite; ghrelin

Outcome Measures

Primary Outcomes (1)

• Blood glucose

  Changes in blood after a 4hour OGTT (75 g glucose)

  4 hours

Secondary Outcomes (3)

• insulin

  4 hours

• incretins

  4 hours

• c-peptid

  4 hours

Study Arms (3)

Screening/Baseline

NO INTERVENTION

A standard OGTT with no supplementation/intervention

Non-hydrolyzed pine nut oil

EXPERIMENTAL

Standard OGTT supplemented with 3 g of non-hydrolyzed pine nut oil

Dietary Supplement: Pine nut oil

hydrolyzed pine nut oil

EXPERIMENTAL

Standard OGTT supplemented with 3 g of hydrolyzed pine nut oil

Dietary Supplement: Pine nut oil

Interventions

Pine nut oil DIETARY_SUPPLEMENT

Subjects are supplemented with either no oil, hydrolyzed oil or non-hydrolyzed oil in combination with an OGTT

Non-hydrolyzed pine nut oil; hydrolyzed pine nut oil

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy, normal weight or overweight (BMI 18, 5-30 inclusive), normal glucose tolerance, non-smoker, no gastrointestinal diseases or operations, normal EKG, normal blood values (liver, kidneys, and hematology), normal blood pressure, no first relatives with diabetes, no prescriptive medicine, informed consent.

You may not qualify if:

• pregnancy, breastfeeding women, food allergies of importance, dietary supplements, special diets, weight change within 3 months, difficulties with consumption of capsules.

Sponsors & Collaborators

• Odense University Hospital: lead

Related Publications (1)

• Sorensen KV, Korfitzen SS, Kaspersen MH, Ulven ER, Ekberg JH, Bauer-Brandl A, Ulven T, Hojlund K. Acute effects of delayed-release hydrolyzed pine nut oil on glucose tolerance, incretins, ghrelin and appetite in healthy humans. Clin Nutr. 2021 Apr;40(4):2169-2179. doi: 10.1016/j.clnu.2020.09.043. Epub 2020 Oct 2.

  PMID: 33059911 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MSc

Model Details: Subjects complete three oral glucose tolerance test (OGTT) on different days, with a minimum of one week in between. First visit is a combined screening and baseline OGTT, with no supplementation. The second and third visit subjects are randomly assigned to either 1 g of non-hydrolyzed pine nut oil or 1 g of hydrolyzed pine nut oil.

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: February 23, 2017
• Study Start: February 1, 2016
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 13, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share