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Updated: Jun 12, 2025
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Orexins mitigate obesity-associated dysfunctions in mice
Anne Blais1, Isabelle Denis1, Mireille Andriamihaja1
1UMR-PNCA, Université Paris-Saclay, AgroParisTech, Palaiseau, France.
Objective:
Obesity is a chronic disease that affects more than 400 million adults with severe comorbidities. The search for new treatments to reduce its negative consequences is necessary. Orexins are hypothalamic neuropeptides involved in various physiological processes related to obesity. The aim of this study was to investigate the consequences of chronic orexin-A treatment in mouse models.
Methods:
Female wild-type C57BL/6 mice that were obesity-prone or obesity-resistant and mice that were deficient for orexin receptors were fed with a high-fat diet. Glucose tolerance, indirect calorimetry, expression of brain neuropeptides and receptors, microglial activation, and microbiota were determined to evaluate the role of orexins on metabolic flexibility.
Results:
Orexin-A reduces weight gain in obesity-prone mice. This reduction is associated with a decrease in body fat, food intake, steatosis, and insulin resistance, as well as alterations of intestinal microbiota composition. A decreased expression of orexin receptors and neuropeptides involved in food intake was also observed in the hypothalamus.
Conclusions:
Our data support the notion that orexin receptor signaling is involved in different aspects of energy metabolism and can mitigate several dysfunctions associated with obesity, suggesting that orexin receptors can represent new targets for obesity treatment.
Insights
Orexin-A treatment reduced weight gain and improved metabolic health in obese mice. This suggests orexin receptors are potential therapeutic targets for treating obesity and its related complications.
Area of Science:
- Neuroscience
- Metabolic Research
- Obesity Studies
Background:
- Obesity is a widespread chronic disease with significant comorbidities.
- Orexins, hypothalamic neuropeptides, play a role in physiological processes linked to obesity.
Purpose of the Study:
- To investigate the effects of chronic orexin-A administration in mouse models of obesity.
- To evaluate the role of orexin signaling in metabolic flexibility.
Main Methods:
- Utilized obesity-prone and resistant C57BL/6 mice, and orexin receptor-deficient mice fed a high-fat diet.
- Assessed glucose tolerance, indirect calorimetry, neuropeptide/receptor expression, microglial activation, and gut microbiota.
Main Results:
- Orexin-A administration decreased weight gain, body fat, food intake, and insulin resistance in obesity-prone mice.
- Observed alterations in intestinal microbiota composition and reduced hypothalamic expression of orexin receptors and feeding-related neuropeptides.
- Orexin-A treatment mitigated steatosis and improved metabolic flexibility.
Conclusions:
- Orexin receptor signaling is implicated in energy metabolism regulation.
- Targeting orexin receptors may offer a novel therapeutic strategy for managing obesity and associated metabolic dysfunctions.
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