Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent µ-/δ-opioid receptor antagonist, regulates obese-related factors in mice
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Orally active dual μ-/δ-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2) was applied to study body weight gain, fat content, bone mineral density, serum insulin, cholesterol and glucose levels in female ob/ob (B6.V-Lep/J homozygous) and lean wild mice with or without voluntary exercise on wheels for three weeks, and during a two week post-treatment period under the same conditions. MZ-2 (10 mg/kg/day, p.o.) exhibited the following actions: (1) reduced body weight gain in sedentary obese mice that persisted beyond the treatment period without effect on lean mice; (2) stimulated voluntary running on exercise wheels of both groups of mice; (3) decreased fat content, enhanced bone mineral density (BMD), and decreased serum insulin and glucose levels in obese mice; and (4) MZ-2 (30 μM) increased BMD in human osteoblast cells (MG-63) comparable to naltrexone, while morphine inhibited mineral nodule formation. Thus, MZ-2 has potential application in the clinical management of obesity, insulin and glucose levels, and the amelioration of osteoporosis.
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These results were replicated in a murine model, in which treatment with morphine inhibited mineral nodule formation, and in human bone marrow-derived mesenchymal stem cells, where morphine altered the ability of mesenchymal stem cells to differentiate into adipocytes or osteoblasts.
“These results were replicated in a murine model, in which treatment with morphine inhibited mineral nodule formation (207), and in human bone marrow-derived mesenchymal stem cells, where morphine altered the ability of mesenchymal stem cells to differentiate into adipocytes or osteoblasts (206).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [207]
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Experimental — accuracy not yet measuredData from in vitro experiments on animal and human cells, as well as in animal models, indicate that opioids can reduce BMD by directly influencing osteoblast activity.
“Data deriving from in vitro experiments on animal and human cells, as well as in animal models indicate that opioids can reduce BMD by directly influencing osteoblast activity (205-210).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [207]
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- Authors
- Marczak, E. D., Jinsmaa, Y., Myers, P. H., Blankenship, T., Wilson, R., Balboni, G., Salvadori, S., & Lazarus, L. H.
- Affiliations
- National Institute of Environmental Health Sciences (US)
- National Institutes of Health (US)
- University of Cagliari (IT)
- University of Ferrara (IT)
- Corresponding author
- Marczak, Ewa D.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 616
- Issue
- 1-3
- Pages
- 115-121
- ISSN
- 0014-2999 (ISSN-L)
- PMC
- PMC2750889
- OpenAlex
- W2034968772
- Semantic Scholar
- f8ca41b17e8e0867bdf02cb9f6ed8b4757d89cad
- Cited by
- 22
- References
- 49
- Citations by year
- 2024: 2 · 2022: 1 · 2021: 2 · 2019: 3 · 2015: 2 · 2014: 3 · 2012: 3
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- National Institutes of Health (NIH0011846955)
- National Institute of Environmental Health Sciences (Z01ES100472, Z01ES090053)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- mu-opioid receptor antagonist, delta-opioid receptor antagonists, obesity, weight gain, fat content, bone mineral density, osteoporosis, insulin, glucose, serum cholesterol, voluntary wheel running, ob/ob mice, osteoblast mineralization, naltrexone, morphine
- MeSH terms
- Adipose Tissue, Administration, Oral, Animals, Body Weight, Cell Line, Eating, Female, Humans, Insulin, Minerals, Obesity, Oligopeptides, Osteoblasts, Physical Conditioning, Animal, Sodium Chloride, Bone Density, Receptors, Opioid, mu, Receptors, Opioid, delta, Cell Proliferation, Mice
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