GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Is there altered sensitivity to ghrelin-receptor ligands in leptin-deficient mice?: importance of satiety state and time of day.
Finger. Beate C BC; Schellekens. Harriët H; Dinan. Timothy G TG; Cryan. John F JF
Key Findings
- Ghrelin increases food intake in both normal and leptin‑deficient mice regardless of time of day.
- The ghrelin‑receptor antagonist D‑Lys(3)-GHRP‑6 only suppresses eating in leptin‑deficient mice during the dark cycle, not the light cycle.
- Fasting reduces the antagonist’s effectiveness in leptin‑deficient mice, and ghrelin‑receptor expression rises in the dark cycle in these mice.
Practical Outcomes
- For biohackers interested in appetite control, timing matters: ghrelin‑blocking compounds may work better at night and when not in a fasted state. Leptin status (or low leptin conditions) could influence how strong the effect is. This suggests that dosing ghrelin antagonists like GHRP‑6 should consider circadian rhythm and recent food intake for optimal results.
Summary
The study shows that mice lacking leptin (ob/ob mice) react differently to ghrelin (a hunger hormone) and a ghrelin blocker (D‑Lys(3)-GHRP‑6) depending on the time of day and whether they are hungry or fed. Ghrelin always makes them eat more, but the blocker only reduces eating in these mice during the night (dark cycle) and when they aren't fasting. The brain’s ghrelin and its receptor levels also change with the light‑dark cycle.
Abstract
Several fine-tuned and interconnected hypothalamic peptidergic systems orchestrate the regulation of energy homeostasis in the body. The orexigenic peptide ghrelin and the anorexigenic peptide leptin are among the most important, and both have been implicated in the development of eating disorders from obesity to anorexia nervosa. The goal of these studies was to examine the response of leptin-deficient ob/ob mice in ghrelin-receptor ligands in a food intake task. Changes in cumulative food intake were measured after peripheral administration of ghrelin (1 and 2 nmol/10 g) and the ghrelin-receptor antagonist (D-Lys(3))-GHRP-6 (66.6 and 133.3 nmol/10 g) in obese and lean control mice during the light and dark cycle as well as in a state of food restriction. Hypothalamic ghrelin and ghrelin-receptor expression was measured in ob/ob and lean mice at two different timepoints. Ghrelin increased food intake in lean and obese mice in the light and dark cycle, whereas the ghrelin-receptor antagonist caused significantly stronger reduction in food intake in obese mice only in the dark cycle. After fasting, ob/ob mice displayed decreased light cycle sensitivity to the anorexigenic effects of the ghrelin-receptor antagonist. Hypothalamic expression levels of ghrelin were unaltered during the light cycle but decreased during the dark cycle in ob/ob mice; whereas, although unchanged in the light cycle, ghrelin-receptor expression was increased in the dark cycle in obese mice. The functionality and sensitivity of the ghrelinergic system is dependent on the time of day and the satiety state in leptin-deficient ob/ob mice.
Study Information
pubmed
2011
2011-03-05T00:00:00.000Z
10.1007/s00213-011-2234-3
19
34