Evaluation of Botanicals for Mechanisms Related to Appetite and Fat Metabolism

Summary

Excess caloric consumption, particularly from inexpensive, energy dense foods that are high in fat and refined carbohydrates, is a major driver of the global obesity epidemic. Dietary supplements that promote reduced intake of energy dense foods and/or impact the absorption and metabolism of fat and carbohydrates in the body can be used to help consumers control their weight. We identified two separate mechanistic approaches to target these effects.

Diacylglycerol acyltransferase-1 (DGAT-1) is an enzyme involved in the formation of dietary fat into circulating triglycerides within the body. Once dietary fat is digested and absorbed, the resulting fatty acids are re-esterified into triglycerides. Inhibition of DGAT-1 results in delayed and decreased re-esterification of dietary fats into circulating triglycerides. It is hypothesized that this effect may lead to decreased deposition of excess dietary fat as adipose tissue, possibly due to increased fatty acid oxidation in the enterocytes.

Ghrelin is a hormone that is known to stimulate appetite in humans. When calorie dense fatty foods are sensed in the stomach, ghrelin is acylated and activated via ghrelin O-acyltransferase (GOAT). The activation step attaches a medium chain fatty acid to the ghrelin molecule that enables it to transmit a signal in the brain that triggers eating and fat storage in adipose tissue. Interfering with the GOAT pathway will inhibit ghrelin activation and possibly diminish food intake and lipid storage. This concept is supported by animal studies in which weight gain in a high fat diet model is prevented when GOAT is inhibited.

Our objective was to determine whether botanicals demonstrating in vitro DGAT-1 and GOAT inhibition have similar mechanistic effects in the human body. Based on the results of this study, prototype formulas may be developed and clinically- tested for outcomes related to weight management.

Conditions

• Overweight
• Obesity

Interventions

DIETARY_SUPPLEMENT

Placebo

Participants were randomly assigned to receive one of four botanical interventions or placebo.

DIETARY_SUPPLEMENT

Apple

Participants were randomly assigned to receive one of four botanical interventions or placebo.

DIETARY_SUPPLEMENT

Grape

Participants were randomly assigned to receive one of four botanical interventions or placebo.

DIETARY_SUPPLEMENT

Raspberry

Participants were randomly assigned to receive one of four botanical interventions or placebo.

DIETARY_SUPPLEMENT

Apricot/Nectarine

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Sponsors & Collaborators

• Radiant Research

  collaborator OTHER

• Access Business Group

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-05-31

Primary Completion

2012-08-31

Completion

2012-08-31