Tubby gene (Tub-1) regulates life span and fat storage by two independent mechanisms 

July 19, 2005 

Worcester, MA - As the leading cause of type II diabetes, heart disease and hypertension, adult onset obesity is an increasingly troubling global health problem. In an effort to understand the molecular connection between two of the most important predispositions for type II diabetes - obesity and advanced age - researchers at the University of Massachusetts Medical School have determined that a gene in the model system C. elegans does indeed regulate both fat storage and life span, but does so via two distinct and independent mechanisms. 

In the paper "C. elegans tubby regulates life span and fat storage by two independent mechanisms" published in the July 19 issue of Cell Metabolism, Assistant Professor of Molecular Medicine and the Program in Gene Function and Expression Heidi A. Tissenbaum, PhD, and co-authors Arnab Mukhopadhyay, PhD, Bart Deplancke, PhD, and Assistant Professor of Molecular Medicine and the Program in Gene Function and Expression Marian Walhout, PhD, examine the function of tub-1, the worm homolog of the mammalian gene tubby. It is in tubby that one of the few single-gene mutations that cause obesity in mammals can be found.

Understanding that in C. elegans, similar to in mammals, mutations in the tub-1 promote increased fat deposition, Dr. Tissenbaum and colleagues in her laboratory and from the laboratory of Dr. Walhout sought to define the molecular pathway that regulates fat deposition. Their results indicate that the function of fat storage is dependent upon a novel interaction partner, RabGTPase-activating protein (RBG-3), and that mutation in tub-1 also leads to life span extension dependent on daf-16/FOXO. Therefore, the paper demonstrates that tub-1 regulates both life span as well as fat metabolism through two independent pathways. Unlike the insulin-like signaling pathway mutants, the life span phenotype can be uncoupled from the increased fat storage phenotype in tub-1 mutants. This indicates that increased life span is not the result of increased fat storage.

Future research in the Tissenbaum lab will be aimed at identifying and understanding the signaling pathways for these mechanisms and will seek to identify their components with the goal of determining if the mammalian counterparts for these pathways have similar phenotypes.

For a copy of the paper, please visit Cell Metabolism online at http://www.cellmetabolism.org/ 

For more information on the Tissenbaum lab, please visit http://profiles.umassmed.edu/profiles/ProfileDetails.aspx?From=SE&Person=658

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Contact: Kelly Bishop