Identification of Muscle-specific Biomarkers of Fatty Acid Beta-oxidation

Summary

Elevated fat levels within skeletal muscle cells (intramyocellular lipids) are highly correlated with muscle and whole-body insulin resistance, and more prevalent in obesity. The molecular links and metabolic shifts driving this association remain open to debate, but notably, reduced muscle mitochondrial fatty acid (FA) ß-oxidation is more prevalent among insulin-resistant/diabetic persons. Therefore, discovery of biomarkers reflective of the status of an individual's muscle FA ß-oxidation activity or capacity would have tremendous prognostic and diagnostic value in terms of diabetes. Furthermore, characterization of metabolites associated with muscle mitochondrial fat metabolism should uncover candidate signaling factors which tie FA ß-oxidation to insulin signaling. The investigators propose to identify, for the first time, specific biomarkers of muscle FA ß-oxidation using multiple metabolomic analytical platforms to compare metabolite profiles in samples derived from biological systems displaying disparate muscle fat combustion. The current experiment will test whether plasma metabolites and/or metabolite signatures that track efficient muscular FA ß-oxidation can be experimentally increased in obese, insulin-resistant subjects via a diet-exercise regimen designed to improve muscle fitness and FA combustion.

Conditions

• Obesity

Interventions

BEHAVIORAL

Diet and Exercise

Subjects underwent a diet regimen targeted to elicit a 10% weight loss. Diets were designed based on the US Dietary Guidelines with caloric deficits individualized for each subject. Aerobic exercise was monitored over approximately 14 weeks, several times per week, to elicit significantly increased VO2max.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• University of California, Davis

  collaborator OTHER

• University of Alabama at Birmingham

  collaborator OTHER

• University of Ottawa

  collaborator OTHER

• Case Western Reserve University

  collaborator OTHER

• USDA, Western Human Nutrition Research Center

  lead FED

Principal Investigators

• Sean H Adams, PHD · University of California, Davis

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

30 Years

Max Age

50 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-10-31

Primary Completion

2012-06-30

Completion

2012-07-31

Countries

• United States

Study Locations