LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men
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The gastric hormone ghrelin stimulates food intake and increases plasma glucose through activation of the growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) has been proposed to inhibit actions of ghrelin through inverse effects on GHSR activity. Here, we investigate the effects of exogenous LEAP2 on postprandial glucose metabolism and ad libitum food intake in a randomized, double-blind, placebo-controlled, crossover trial of 20 healthy men. We report that LEAP2 infusion lowers postprandial plasma glucose and growth hormone concentrations and decreases food intake during an ad libitum meal test. In wild-type mice, plasma glucose and food intake are reduced by LEAP2 dosing, but not in GHSR-null mice, pointing to GHSR as a potential mediator of LEAP2's glucoregulatory and appetite-suppressing effects in mice.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 100582 |
| Tidsskrift | Cell Reports Medicine |
| Vol/bind | 3 |
| Udgave nummer | 4 |
| ISSN | 2666-3791 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
F.K.K. has served on scientific advisory panels and/or been part of speaker’s bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi, and Zealand Pharma. L.S.G. is in speaker’s bureau for Eli Lilly. T.V. has served on scientific advisory panels for, been part of speaker’s bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. J.J.H. is supported by the Novo Nordisk Foundation Center for Basic Metabolic Research.
Funding Information:
We thank the participants for their commitment to the clinical study; K.H. Rasmussen, D.B. Nielsen, A.H. Klitgaard, and J. Bach for laboratory assistance; and A.M. Ellegaard for critical reading of the manuscript. C.A.H. and S.H. received research grants from the Innovation Fund Denmark (grant number 8053-00026B ) and the Danish Diabetes Academy , respectively. The latter is funded by the Novo Nordisk Foundation (grant number NNF17SA0031406 ). Synthetic LEAP2 used for animal studies was a gift from Novo Nordisk (Bagsværd, Denmark). The graphical abstract was created with BioRender.com .
Funding Information:
We thank the participants for their commitment to the clinical study; K.H. Rasmussen, D.B. Nielsen, A.H. Klitgaard, and J. Bach for laboratory assistance; and A.M. Ellegaard for critical reading of the manuscript. C.A.H. and S.H. received research grants from the Innovation Fund Denmark (grant number 8053-00026B) and the Danish Diabetes Academy, respectively. The latter is funded by the Novo Nordisk Foundation (grant number NNF17SA0031406). Synthetic LEAP2 used for animal studies was a gift from Novo Nordisk (Bagsv?rd, Denmark). The graphical abstract was created with BioRender.com. Conceptualization, C.A.H. and F.K.K.; methodology, C.A.H. L.S.G. M.B.C. B. Holst, and F.K.K.; investigation, C.A.H. M.S.J. and S.H.; resources, C.A.H. S.H. S.B. B. Hartmann, F.D. and J.J.H.; writing ? original draft, C.A.H. and S.H.; writing ? review & editing, C.A.H. M.S.J. S.H. L.S.G. S.B. K.S.-J. B. Hartmann, J.J.H. F.D. T.V. M.B.C. B. Holst, and F.K.K.; supervision, L.S.G. M.B.C. T.V. B. Holst, and F.K.K.; funding acquisition, C.A.H. B. Holst, and F.K.K. F.K.K. has served on scientific advisory panels and/or been part of speaker's bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi, and Zealand Pharma. L.S.G. is in speaker's bureau for Eli Lilly. T.V. has served on scientific advisory panels for, been part of speaker's bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. J.J.H. is supported by the Novo Nordisk Foundation Center for Basic Metabolic Research.
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© 2022 The Author(s)
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