Fat storage pathways in obesity and aging

Univ Of Massachusetts Med Sch Worcester, Worcester MA

Investigators

Abstract

? DESCRIPTION (provided by applicant): Excess adiposity in humans is thought to be the leading cause of metabolic syndrome and projected to result in shortening life expectancy in the near future. However, recent epidemiological, molecular, and genetic evidence suggest that adipose amount does not correlate with an individual's lifespan or metabolic health. Thus, the relationship between fat gain and health outcome still remains elusive. The well characterized insulin/insulin-like growth factor-1 (IGF-1) signaling pathway influences adiposity, longevity, and metabolism in a variety of organisms. Paradoxically, animals bearing mutation in the insulin/IGF-1 signaling (IIS) pathway receptor are obese and long-lived, contrary to animals that have become obese due to poor diet such as a high sugar (HS) diet that are short-lived. Our preliminary data suggests two independent pathways regulate fat storage of the long-lived obese animals and the short-lived obese animals. In this proposal, I will compare the global transcriptional differences between the two cohorts with the goal of identifying genetic markers and molecular pathways that govern the health compatible fat gain seen in long-living IIS mutants. Then, using various imaging techniques, we will also uncover any morphological differences between the two cohorts. While discovery of drug targets that allow for reduction in adipose amount remains the goal of anti-obesity drug therapy, gaining new insights in the cellular and molecular origins of unique and potentially health compatible fat stores may present a new therapeutic avenue for ameliorating age related metabolic abnormalities.