News & Research

    University of Colorado, Aurora, Colorado

Mechanisms for fetal hepatic programming in the non-human primate

General Research Subject: Type 2 Diabetes

Focus: Other

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2008

Project End Date: June 30, 2012

Research Description

There is increasing interest in the hypothesis that exposure to maternal obesity during pregnancy, in the absence of diabetes, may have adverse lifelong consequences in the offspring including juvenile obesity and type II diabetes however, the underlying mechanisms by which fetal metabolic systems cope with excess fuels during intrauterine development remains relatively unexplored. In the current proposal we have developed a nonhuman primate (NHP) model to determine the effect of chronic maternal consumption of a high fat/calorie (HF) diet on the development of metabolic systems in the fetal offspring.

We demonstrate that only a portion of the adult female monkeys chronically consuming the HF diet become obese and insulin resistant. However, irrespective of whether the adult monkey became obese and insulin resistant, all fetal offspring of HF mothers examined during the early 3rd trimester showed signs of hepatic inflammation, oxidative stress/damage, triglyceride accumulation and premature gluconeogenic gene activation. The goal of this research is to investigate whether switching obese mothers to a healthy diet during pregnancy can prevent these complications in the fetus, and furthermore, whether returning to control low fat diet after birth can prevent or reduce many of the abnormalities during post-natal life, particularly the steps that might be causative for juvenile obesity and type II diabetes.

Reseacher Profile

Mentor: Jacob Friedman, PhD   Postdoctoral Fellow: Stephanie Thorn, PhD

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

There is increasing interest in the hypothesis that exposure to maternal obesity during pregnancy, in the absence of diabetes, may have adverse lifelong consequences in the offspring including juvenile obesity and type II diabetes however, the underlying mechanisms by which fetal metabolic systems cope with excess fuels during intrauterine development remains relatively unexplored. In the current proposal we have developed a nonhuman primate (NHP) model to determine the effect of chronic maternal consumption of a high fat/calorie (HF) diet on the development of metabolic systems in the fetal offspring.

We demonstrate that only a portion of the adult female monkeys chronically consuming the HF diet become obese and insulin resistant. However, irrespective of whether the adult monkey became obese and insulin resistant, all fetal offspring of HF mothers examined during the early 3rd trimester showed signs of hepatic inflammation, oxidative stress/damage, triglyceride accumulation and premature gluconeogenic gene activation. The goal of this research is to investigate whether switching obese mothers to a healthy diet during pregnancy can prevent these complications in the fetus, and furthermore, whether returning to control low fat diet after birth can prevent or reduce many of the abnormalities during post-natal life, particularly the steps that might be causative for juvenile obesity and type II diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

We will learn what types of diets are most helpful, and whether shifting calories or the type of fat in the diet matters to pregnant women and their offspring. We hypothesize that too much fat during pregnancy in the absence of gestational diabetes will promote changes in the fetal organs that foreshadow early events in diabetes. When we switch the diet back to normal we can determine whether obesity and a healthy diet can prevent some of the changes observed in the fetus. This study will help us to determine how fat in the diet (currently used in place of carbohydrate) during gestation specifically affects organ development and susceptibility to juvenile obesity.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

We hopefully can prevent some of the changes observed in the fetus to slow down the obesity epidemic. The long-term objective of the University of Colorado Center is to have a comprehensive research center to maintain and develop a program of research aimed at understanding the genetic, molecular, and endocrine origins of fetal growth and pediatric obesity and its complications. This research will help translate our findings into a strong interaction with the UCHSC Pediatric obesity clinics and will have both clinical as well as clinical research components. The clinical research arm will include translational research interventions and population prevention based interventions.

In what direction do you see the future of diabetes research going?

I believe more interdisciplinary research is needed whereby endocrinologists working with experts in behavior, nutrition, biochemistry and clinical scientists is going to help attack the problems we face in diabetes. New therapies will be forthcoming from surprising sources, and thus its important to have multiple approaches to the problems of obesity and diabetes.