Aim: To test the impact of cholecystokinin (CCK) plus either amylin or a glucagon-like peptide-1 receptor (GLP-1R) agonist on metabolic variables in diet-induced obese (DIO) rodents.
Methods: A stabilized acetylated version of CCK-8 (Ac-Y*-CCK-8), selective CCK1 receptor (CCK1R) or CCK2 receptor (CCK2R) agonists, amylin or the GLP-1R agonist and exenatide analogue AC3174 were administered in select combinations via continuous subcutaneous infusion to DIO rats for 14 days, or Lep(ob) /Lep(ob) mice for 28 days, and metabolic variables were assessed.
Results: Combined administration of Ac-Y*-CCK-8 with either amylin or AC3174 induced greater than additive weight loss in DIO rats, with the overall magnitude of effect being greater with AC3174 + Ac-Y*-CCK-8 treatment. Co-infusion of AC3174 with a specific CCK1R agonist, but not a CCK2R agonist, recapitulated the weight loss mediated by AC3174 + Ac-Y*-CCK-8 in DIO rats, suggesting that synergy is mediated by CCK1R activation. In a 4 × 4 full-factorial response surface methodology study in DIO rats, a synergistic interaction between AC3174 and the CCK1R-selective agonist on body weight and food intake was noted. Co-administration of AC3174 and the CCK1R-selective agonist to obese diabetic Lep(ob) /Lep(ob) mice elicited a significantly greater reduction in percentage of glycated haemoglobin and food intake relative to the sum effects of monotherapy groups.
Conclusions: The anti-obesity and antidiabetic potential of combined GLP-1R and CCK1R agonism is an approach that warrants further investigation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/dom.12390 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protective Effects of Dioscin and Diosgenin on Plateau Hyperuricemia by Attenuating Renal Inflammation via EPHX2.
Int J Mol Sci
December 2024
Beijing Institute of Radiation Medicine, Beijing 100859, China.
Plateau hyperuricemia is a common disease in the plateau area, and the incidence is much higher than that in the plain area. Dioscin (DIO) and its active metabolite Diosgenin (DG) exert therapeutic effects on hyperuricemia through oxidative stress and inflammation. In this study, DIO and its active metabolite DG were taken as the research objects to explore their therapeutic effects on high-altitude hyperuricemia in rats.
View Article and Find Full Text PDFCharacterization of LY3324954 a long-acting glucagon-receptor agonist.
Mol Metab
January 2025
Comprehensive Diabetes Center and Department of Medicine - Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:
Article Synopsis
- * Researchers developed a new glucagon receptor agonist, LY3324954, that has better potency and effectiveness compared to regular glucagon, and it showed a prolonged impact in various animal models.
- * In tests, LY3324954 led to increased energy expenditure, weight loss, and better fat management in diet-induced obese mice, indicating its potential as a therapeutic option for obesity-related conditions.
[Reoxygenation improves reduced hypothalamic leptin responsiveness induced by intermittent hypoxia in obese rats].
Nan Fang Yi Ke Da Xue Xue Bao
September 2024
Department of Psychiatry (Sleep Medicine Center), School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
Objective: To evaluate the effects of intermittent hypoxia-reoxygenation (IHR) on body weight, diet and water intake, circulating metabolites, and responses to central leptin injection in a rat model of diet-induced obesity (DIO).
Methods: Rat models of DIO established by 12-week high-fat diet (HFD) feeding were randomized into normoxia group (=15), intermittent hypoxia group (6% O, 30 cycles/h, 8 h/day for 4 weeks; =15), and IHR group (2 weeks of intermittent hypoxia followed by 2 weeks of reoxygenation; =15). Body weight, diet and water intake of the rats were recorded, and circulating leptin, IL-6, and Ang-II levels were detected.
Cafeteria diet and caloric restriction affect metabolic but not behavioral characteristics in male Wistar rats.
Physiol Behav
January 2025
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address:
This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period.
View Article and Find Full Text PDFEffects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats.
bioRxiv
September 2024
VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA 98108, USA.
Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!