NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats
Abstract
Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effects in vivo. Obese models were established using high-fat/high-sucrose-fed for 5 months. NEU-P11 (10mg/kg)/melatonin (4mg/kg)/vehicle were administered by a daily intraperitoneal injection respectively for 8 weeks. Our results showed that NEU-P11 or melatonin inhibited both body weight gain and deposit of abdominal fat with no influence on food intake. The impaired insulin sensitivity and antioxidative potency were improved and the levels of plasma glucose, total cholesterol (TC), triglycerides (TG) decreased with an increased in HDL-cholesterol (HDL-c) after NEU-P11 or melatonin administration. These data suggest that NEU-P11, like melatonin, decreased body weight gain and improved insulin sensitivity and metabolic profiles in obese rats. We conclude that NEU-P11 has a melatoninergic effect on regulating body weight in obese rats and also improving metabolic profiles and efficiently enhancing insulin sensitivity.
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The underlying mechanism of melatonin in amelioration of insulin sensitivity encompasses induction of β-cell regeneration, hepatic glycogen synthesis promotion which reduce hyperglycemia in an animal model.
“The underlying mechanism of melatonin in amelioration of insulin sensitivity encompasses induction of β -cell regeneration, hepatic glycogen synthesis promotion which reduce hyperglycemia in an animal model. 13,27,28”
From Melatonin supplementation improves glycemic hemostasis, lipid profile, and adipokine concentrations of obese women: A double-blind randomized clinical trial (2024) · cites this paper as [27]
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“13,27,28 Furthermore, melatonin prevents insulin resistance by activating the cyclic adenosine monophosphate (cAMP)- response element binding protein (CREB)-peroxisome proliferator-activated receptor gamma coactivator 1-(PGC-1α) pathway.”
- Authors
- She, M., Deng, X., Guo, Z., Laudon, M., Hu, Z., Liao, D., Hu, X., Luo, Y., Shen, Q., & Su, Z.
- Affiliations
- University of South China (CN)
- Neurim Pharmaceuticals (Israel) (IL)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 59
- Issue
- 4
- Pages
- 248-253
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W1997463511
- Cited by
- 118
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 12 · 2012: 6
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- melatonin receptor agonists, melatonin, obesity, insulin sensitivity, insulin resistance, high-fat high-sugar diet, weight gain, abdominal fat, oxidative stress, lipid metabolism, HDL cholesterol, sleep disorders
- MeSH terms
- Animals, Body Weight, Dietary Fats, Eating, Glucose, Insulin, Male, Melatonin, Obesity, Random Allocation, Body Mass Index, Rats, Sprague-Dawley, Oxidative Stress, Dietary Sucrose, Receptors, Melatonin, Rats
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