Regulation of Metabolism by Nitric Oxide

Confocal image of mitochondria in a living adipose tissue explant derived from eNOS-TG mice. Boxes indicate putative APCs with high mitochondrial levels. Red, TMRM; Blue, Hoescht.

Our metabolomic analyses indicate that eNOS overexpression increases the abundance of circulating bile acids, which have been shown to be potent effectors of metabolism and regulators of adipose tissue phenotype. We are testing the hypothesis that NO exerts an anti-obesogenic effect by regulating bile acid metabolism, which promotes the development of adipocytes into a novel “lean” phenotype characterized by high mitochondrial content and fat burning capacity. To test this hypothesis, we will:

  • Examine the effects of NO on diet-induced obesity;
  • Determine how NO regulates metabolism; and
  • Elucidate the mechanisms regulating adipocyte phenotype.

The experimental approaches in these aims will test whether NO directly regulates obesity and whether the anti-obesity effects of NO are mediated through the ability of eNOS to increase bile acid production and to regulate adipose tissue phenotype. These studies could lay the groundwork for the development of novel therapeutic interventions to prevent, manage or reverse obesity and insulin resistance.

Principal Investigator

Bradford Hill, PhD />
<h3>Bradford Hill, Ph.D.</h3>
<p>Assistant Professor of Medicine<br />
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Bradford Hill, Ph.D.

Assistant Professor of Medicine
E-mail Bradford Hill

Ph.D., University of Louisville
Postdoctoral studies, University of Alabama-Birmingham: free radical biology and bioenergetics

Research Interests:
Diabetes and the function and physiology of mitochondria, with an emphasis on their role in causing myocardial insulin resistance.

Related publications:
Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal

The Hitchhiker's Guide to XF Bioenergetic Assays

What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology