ArticleInternational journal of obesity (2005)2018
Neuromodulation of orexin neurons reduces diet-induced adiposity.
Article in International journal of obesity (2005), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
- Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity.Nutrients · 2026Trial
- Sex-specific circadian and behavioral phenotypes in aged growth hormone receptor knockout mice.GeroScience · 2026Article
- Inhibition of the lateral hypothalamus emboldens adult female spiny mice to huddle with an established group of novel peers.Scientific reports · 2025Article
- Interaction between corticotropin-releasing factor, orexin, and dynorphin in the infralimbic cortex may mediate exacerbated alcohol-seeking behavior.Neurobiology of stress · 2024Article
- Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance.Brain sciences · 2024Article
- Obesity: A Review of Pathophysiology and Classification.Mayo Clinic proceedings · 2023Review
- Daily treatment with the dual orexin receptor antagonist DORA-12 during oxycodone abstinence decreases oxycodone conditioned reinstatement.Neuropharmacology · 2023Article
- Review
- Locus coeruleus input-modulated reactivation of dentate gyrus opioid-withdrawal engrams promotes extinction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- The Fidget Factor and the obesity paradox. How small movements have big impact.Frontiers in sports and active living · 2023Article
- Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats.Frontiers in pharmacology · 2023Article
- Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain.Frontiers in cellular neuroscience · 2023Article
- Orexin and MCH neurons: regulators of sleep and metabolism.Frontiers in neuroscience · 2023Review
- Body Weight and Metabolic Rate Changes in Narcolepsy: Current Knowledge and Future Directions.Metabolites · 2022Review
- Chronic chemogenetic manipulation of ventral pallidum targeted neurons in male rats fed an obesogenic diet.Brain research · 2022Article
- The physiological control of eating: signals, neurons, and networks.Physiological reviews · 2022 · on this mapArticle
- Orexin, serotonin, and energy balance.WIREs mechanisms of disease · 2022Review
- The PACAP Paradox: Dynamic and Surprisingly Pleiotropic Actions in the Central Regulation of Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Serotonin, food intake, and obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- Effects of exercise and diet intervention on appetite-regulating hormones associated with miRNAs in obese children.Eating and weight disorders : EWD · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND/
objectivesLow levels of orexin are associated with obesity and reduced physical activity in humans and animals. SUBJECTS/
methodsDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated orexin neurons in mouse lateral hypothalamus (LH) to measure effects on spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic injection of AAV vectors into caudal lateral LH of heterozygous orexin-Cre or C57/B6J mice. In one set of studies, excitation of orexin neurons was examined (virus: AAV2-EF1a-DIO-hM3Dq-mCherry), and test sessions began 3-4 h after light cycle onset. In a study examining the inhibition of orexin neurons (virus: AAV2-hSyn-DIO-hM4Di-mCherry), testing began 15 min prior to dark cycle onset. Clozapine n-oxide (CNO; 1 or 5 mg/kg) or saline was injected intraperitoneally and time spent moving in open field chambers was recorded for 2 h. Follow-up studies in separate mouse cohorts quantified SPA in parallel with changes in energy expenditure (EE) and chow intake using indirect calorimetry chambers (SableSystem™). Following acclimation, testing sessions (saline and/or CNO) took place over the course of ~1 week, with injections administered every day. Changes in SPA, EE, chow intake, fecal boli, and body composition (EchoMRI™) were measured. Additional mice cohorts were fed a high-fat diet (HFD) and injected with CNO daily up to 10 days to assess the potential for orexin activation to prevent diet-induced obesity.
resultsActivation of orexin resulted in increases in SPA in male and female mice, and was accompanied by increases in energy expenditure without changes in overall chow intake. When orexin activation occurred in the context of high fat diet, weight gain and adiposity were significantly attenuated. SPA was decreased when DREADDs were used to inhibit orexin activity.
conclusionThese results demonstrate that orexin neurons play a critical role in mediating physical activity and suggest a novel therapeutic target for treating obesity.
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