GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Crosstalking between the "gut-brain" hormone ghrelin and the circadian system in the goldfish. Effects on clock gene expression and food anticipatory activity.
Nisembaum. Laura G LG; de Pedro. Nuria N; Delgado. María J MJ; Isorna. Esther E
Key Findings
- Acute ghrelin injection doubled expression of some Per clock genes in hypothalamus and liver.
- Ghrelin also increased hypothalamic orexin, linking hunger signaling to wakefulness.
- A ghrelin antagonist ([D‑Lys(3)]‑GHRP‑6) blocked food‑anticipatory activity in fish, indicating endogenous ghrelin’s role in pre‑meal rhythms.
Practical Outcomes
- For biohackers, this suggests that manipulating ghrelin (e.g., with GHRP‑6) could affect your internal clock and hunger cues, but the evidence is from fish and not directly transferable. Any dosing or timing protocols for humans remain speculative, and more human‑focused research is needed before applying these findings.
Summary
In goldfish, giving ghrelin (the hunger hormone) changed the activity of clock genes in the brain and liver and boosted orexin, a wake‑up signal. Blocking ghrelin with a GHRP‑6‑based antagonist stopped the fish’s normal pre‑feeding activity, suggesting ghrelin helps drive the body’s food‑anticipation clock. While the work is in fish and uses injections, it hints that ghrelin can influence circadian rhythms and appetite timing.
Abstract
Ghrelin is a potent orexigenic signal mainly synthesized in the stomach and foregut of vertebrates. Recent studies in rodents point out that ghrelin could also act as an input for the circadian system and/or as an output of peripheral food-entrainable oscillators, being involved in the food anticipatory activity (FAA). In this study we pursue the possible interaction of ghrelin with the circadian system in a teleost, the goldfish (Carassius auratus). First, we analyzed if ghrelin is able to modulate the core clock functioning by regulating clock gene expression in fish under a light/dark cycle 12L:12D and fed at 10 am. As expected the acute intraperitoneal (IP) injection of goldfish ghrelin (gGRL[1-19], 44 pmol/g bw) induced the expression of hypothalamic orexin. Moreover, ghrelin also induced (∼ 2-fold) some Per clock genes in hypothalamus and liver. This effect was partially counteracted in liver by the ghrelin antagonist ([D-Lys(3)]-GHRP-6, 100 pmol/g bw). Second, we investigated if ghrelin is involved in daily FAA rhythms. With this aim locomotor activity was studied in response to IP injections (5-10 days) of gGRL[1-19] and [D-Lys(3)]-GHRP-6 at the doses above indicated. Ghrelin and saline injected fish showed similar 24h activity patterns. However, ghrelin antagonist treatment abolished the FAA in schedule fed fish under 24h light, suggesting the involvement of the endogenous ghrelin system in this pre-feeding activity. Altogether these results suggest that ghrelin could be acting as an input for the entrainment of the food-entrainable oscillators in the circadian organization of goldfish.
Study Information
pubmed
2014
2014-03-27T00:00:00.000Z
10.1016/j.ygcen.2014.03.016
36
58