Physiological mechanisms of sustained fumagillin-induced weight loss.

Journal Article (Journal Article)

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss-inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction.

Full Text

Duke Authors

Cited Authors

  • An, J; Wang, L; Patnode, ML; Ridaura, VK; Haldeman, JM; Stevens, RD; Ilkayeva, O; Bain, JR; Muehlbauer, MJ; Glynn, EL; Thomas, S; Muoio, D; Summers, SA; Vath, JE; Hughes, TE; Gordon, JI; Newgard, CB

Published Date

  • March 8, 2018

Published In

Volume / Issue

  • 3 / 5

PubMed ID

  • 29515039

Pubmed Central ID

  • PMC5922281

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.99453


  • eng

Conference Location

  • United States