News & Research

    University of Southern California, San Francisco, San Francisco, California

Melanocortin-specific micro RNAs: identification, function and role in human obesity

General Research Subject: Obesity

Focus: Integrated Physiology, Integrated Physiology\Regulation of Food Intake, Obesity, Obesity\Animal Models, Obesity\Pathogenesis

Type of Grant: ADA-Novo Nordisk Award in Neurohormonal Control of Metabolism

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

By dramatically raising the rate of diabetes, obesity has become a major public health concern for the 21st century. Both environmental and genetic factors are involved in the onset and progression of weight gain. Our long-term objective is to identify gene mutations that predispose humans to obesity and to understand how they cause obesity. We have already found that mutations in genes such as POMC, a neuro-hormonal precursor in the brain, or the Melanocortin-4 receptor, which is a receptor for these neuro-hormones, can predispose to severe obesity and to early childhood onset obesity. It is also suspected that dysfunction of the cells making these factors could predispose humans to obesity. 

In this project we propose to characterize the role of a novel class of genes, microRNA , in the function of the POMC cells.  Specifically, in this project we will determine the nature of the microRNA that are in the POMC cells, determine the metabolic effects of their ablation in mice and determine if mutations in these genes play a role in human obesity. The overall objective of our studies is to develop new approaches to find gene variations that could predispose human to severe obesity in order to identify new therapeutic targets for this condition.

Research Profile

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

Obesity, and in particular severe obesity, is a major predisposing condition for type II diabetes. Although obesity has been long known to run in families, it is not until recently that genes causing obesity in humans have been discovered. All of these genes encode proteins that are implicated in the regulation of food intake by the brain. Our laboratory is at the forefront of finding such genes in which mutations cause human obesity and in understanding how these genes regulate the balance between energy expenditure and food intake and how they participate in the control of blood glucose.                                                    

In this project we will determine whether a new recently discovered class of genes, called microRNA, are important for the function of the neurons that are involved in the regulation of food intake and energy metabolism. Specifically, this project will allow us to make an inventory of the genes that are expressed in these neurons, to determine their role in the function of these neurons and to determine whether mutations in this genes could predispose humans to obesity.

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

Obesity and in particular severe, is the most common and rapidly growing nutritional problem in westernized countries. Obesity is the major risk factor for type II diabetes. By understanding what genes contribute to obesity and how these genes contribute to obesity, we hope to better understand the underlying causes of the obesity epidemic and help prevent the rise in type II diabetes.

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

Our long-term scientific objectives are to identify gene mutations causing obesity or type II diabetes in humans, to understand their pathogenic effects and to determine if these mutations influence the outcome of therapeutic interventions. This research award will allow us to determine the role of microRNAs, a recently discovered class of genes, in the genetic predisposition to human obesity. This award is directly relevant to our research effort, and will allow us to rapidly start on a very novel and promising research avenue in diabetes research.

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

Although numerous major advances are underway in the treatment of this condition, we are faced with the reality that the number of people diagnosed with diabetes, both type I and type II, is increasing steadily. Understanding the reasons for this increase as well as developing strategies to prevent it will be the major challenge for future diabetes research.