Kisspeptin-10 Ameliorates Obesity-Diabetes with Diverse Effects on Ileal Enteroendocrine Cells and Pancreatic Islet Morphology in High-Fat Fed Female Mice.
Sridhar. Ananyaa A; Khan. Dawood D; Muthukumar. Rithiga R; Sampathkumar. Swetha S; Irwin. Nigel N; Flatt. Peter R PR; Moffett. R Charlotte RC
Key Findings
- Kisspeptin-10 reduced weight, glucose levels, and energy intake in high‑fat‑fed female mice.
- It altered ileal enteroendocrine cell composition, increasing GIP‑positive cells and normalising GLP‑1 levels.
- Beta‑cell proliferation increased, restoring insulin‑producing area toward normal levels.
Practical Outcomes
- The data suggest kisspeptin‑10 could influence metabolism by acting on the gut‑pancreas axis, but the study used injectable doses in mice, not humans. For biohackers, it’s an interesting proof‑of‑concept that may inspire future oral or peptide formulations, yet there’s no ready‑to‑use protocol or safety data for people.
Summary
In a mouse study, giving kisspeptin-10 twice daily for three weeks lowered body weight, blood sugar, and food intake in high‑fat‑diet females, making them look like mice on a normal diet. It also changed gut hormone‑producing cells and boosted the growth of insulin‑producing beta cells in the pancreas, without harming the cells.
Abstract
Kisspeptin is a neuropeptide recognised for a pivotal role within the reproductive system, but potentially important endocrine metabolic effects are less well understood. We examined effects of twice-daily intraperitoneal administration of saline vehicle or kisspeptin-10 (25 nmol/kg), for 21 days, on glucose homeostasis, energy balance, circulating hormones as well as the morphology-function of enteroendocrine and islet cells in high-fat diet (HFD) fed female mice, with normal diet (ND) mice as an additional control group. Kisspeptin-10 decreased body weight, blood glucose and energy intake to ND levels. HFD increased circulating follicle-stimulating hormone (FSH) levels, which were further enhanced by kisspeptin-10 along with luteinising hormone (LH) concentrations. Neither HFD nor kisspeptin-10 affected progesterone or corticosterone. In the ileum, kisspeptin-10 decreased crypt depth and restored villi length to ND control levels, as well as increasing the proportion of glucose-dependent insulinotropic polypeptide (GIP) positive cells when compared to HFD mice and glucagon-like peptide-1 (GLP-1) positive cells compared to ND mice. Peptide YY (PYY) immunoreactivity was unaltered by HFD or kisspeptin-10. Plasma GIP was unchanged but circulating GLP-1 and PYY were reduced to ND levels. Within the pancreas, total islet, beta- and alpha-cell areas were similar in all mice, but kisspeptin-10 intervention restored relative insulin area to ND levels. Glucagon radius, an indicator of peripherally located alpha-cells, was reduced in HFD mice but normalised by kisspeptin-10 alongside elevated glucagon-islet area. Notably, beta-cell proliferation was increased by kisspeptin-10 with no alteration in beta-cell apoptosis. Overall, we reveal a previously uncharacterised diverse metabolic role for kisspeptin in directly modulating the gut-pancreatic axis.
Study Information
pubmed
2025
2025-11-13T00:00:00.000Z
10.3390/biom15111591
57