Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.
Endocrinology
; 154(2): 709-17, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23307790
Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diet, Reducing
/
Ghrelin
/
Diet, High-Fat
Limits:
Animals
Language:
En
Journal:
Endocrinology
Year:
2013
Document type:
Article