Physiological mechanisms of sustained fumagillin-induced weight loss.
JCI Insight
; 3(5)2018 03 08.
Article
en En
| MEDLINE
| ID: mdl-29515039
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Bacterias
/
Ciclohexanos
/
Metabolismo Energético
/
Ácidos Grasos Insaturados
/
Microbioma Gastrointestinal
/
Obesidad
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Año:
2018
Tipo del documento:
Article