GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin signaling in the ventral tegmental area mediates both reward-based feeding and fasting-induced hyperphagia on high-fat diet.
Wei. X J XJ; Sun. B B; Chen. K K; Lv. B B; Luo. X X; Yan. J Q JQ
Key Findings
- Ghrelin microinjection into the VTA causes a dose‑dependent increase in reward‑driven high‑fat feeding in sated rats, leading to weight gain.
- The same VTA ghrelin injection amplifies fasting‑induced hyperphagia (overeating) on a high‑fat diet, also producing extra weight gain.
- Co‑administration of the ghrelin receptor antagonist D‑Lys3‑GHRP‑6 blocks both the reward‑based and fasting‑induced overeating effects.
Practical Outcomes
- Using GHRP‑6 may heighten cravings for tasty, high‑fat foods and promote weight gain, especially if taken when you’re not hungry or after a long fast. Timing and dose matter—lower or spaced doses might reduce the hedonic eating drive. If you want to blunt these effects, a ghrelin‑receptor blocker (e.g., D‑Lys3‑GHRP‑6) could be considered, though it’s not widely available for personal use.
Summary
Injecting ghrelin (or using a ghrelin‑like peptide such as GHRP‑6) directly into a brain area called the ventral tegmental area makes rats eat a lot more high‑fat food, even when they’re not hungry, and it adds extra weight. The same boost happens after a long fast, and both effects can be stopped by a ghrelin‑receptor blocker (D‑Lys3‑GHRP‑6).
Abstract
Ghrelin is a potent orexigenic hormone that acts in the central nervous system to stimulate food intake via the growth hormone secretagogue receptor (GHSR) that is abundantly expressed in the ventral tegmental area (VTA). Not only does ghrelin modulate feeding behavior via a homeostatic mechanism, but numerous studies have identified ghrelin as a key regulator of reward-based hedonic feeding behaviors. Nutritional states influence ghrelin and GHSR expression as well as the behavioral sensitivity to reward-inducing stimuli. In the current study, we examined the role of ghrelin at the VTA level in food intake in two different nutritional states, satiety and hunger, by using a restricted feeding model. In this model, rats were conditioned to a daily 3-h (h) feeding session on standard chow for 10days and a high-fat diet (HFD) was supplied either in the third hour after 2h of chow diet intake, or at the beginning of a daily meal on the test day. We found that intra-VTA microinjection of 1, 2, and 4μg of ghrelin, induced a dose-related increase of 1h of reward-based feeding on HFD in sated rats, as well as a 24-h body weight gain. The overconsumption stimulated by ghrelin could be attenuated by 10μg of direct infusion of the ghrelin receptor antagonist D-Lys3-GHRP-6 into the VTA. Moreover, our data showed that the injection of 1, 2, and 4μg of ghrelin in the VTA, enhanced fasting-induced hyperphagia on HFD in a dose-related manner following a 21-h food restriction as well as a 24-h body weight gain. Conversely, hyperphagia on HFD that is potentiated by ghrelin could be blocked by pretreatment with a 10-μg D-Lys3-GHRP-6 intra-VTA microinjection. Collectively, these data demonstrate that ghrelin signaling at the VTA level mediates both reward-based eating and fasting-induced hyperphagia and provides a primary target for the control of the intake of rewarding food.
Study Information
pubmed
2015
2015-05-09T00:00:00.000Z
10.1016/j.neuroscience.2015.05.001
42
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