| First Author | Briggs DI | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 2 | Pages | 709-17 |
| PubMed ID | 23307790 | Mgi Jnum | J:195433 |
| Mgi Id | MGI:5484473 | Doi | 10.1210/en.2012-1421 |
| Citation | Briggs DI, et al. (2013) 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 |
| abstractText | 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. |
