Walker RG, Barrandon O, Poggioli T, Dagdeviren S, Carroll SH, Mills MJ, Mendello KR, Gomez Y, Loffredo FS, Pancoast JR, Macias-Trevino C, Marts C, LeClair KB, Noh HL, Kim T, Banks AS, Kim JK, Cohen DE, Wagers AJ, Melton DA, Lee RT. 2020. Exogenous GDF11, but not GDF8, reduces body weight and improves glucose homeostasis in mice. Scientific reports. 10(1):4561. Pubmed: 32165710 DOI:10.1038/s41598-020-61443-y


Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of exogenous rGDF11 reduced body weight by 3-17% and significantly improved glucose tolerance in aged mice fed a chow (~30% vs. saline) or HF (~50% vs. saline) diet and young mice fed a HFD (~30%). On the other hand, exogenous rGDF8 showed signifcantly lesser effect or no effect at all on glucose tolerance compared to rGDF11, consistent with data demonstrating that GFD11 is a more potent signaling ligand than GDF8. Collectively, our results show that administration of exogenous rGDF11, but not rGDF8, can reduce diet-induced weight gain and improve metabolic homeostasis.

Related Faculty

Photo of Amy Wagers

Amy Wagers seeks to change the way we repair our tissues after an injury. Her research focuses on defining the factors and mechanisms that regulate the migration, expansion, and regenerative potential of adult blood-forming and muscle-forming stem cells.

Photo of Rich Lee

Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.

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