ArticleMolecular metabolism2020
Regulation of muscle and metabolic physiology by hypothalamic erythropoietin independently of its peripheral action.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- A direct effect of the hematocrit on blood glucose: Evidence from hypoxia- and erythropoietin-treated mice.Science advances · 2025Article
- Review
- Huaiyu pill alleviates inflammatory bowel disease in mice blocking toll like receptor 4/ myeloid differentiation primary response gene 88/ nuclear factor kappa B subunit 1 pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Hypothalamic control of energy expenditure and thermogenesis.Experimental & molecular medicine · 2022Review
- Erythropoietin Non-hematopoietic Tissue Response and Regulation of Metabolism During Diet Induced Obesity.Frontiers in pharmacology · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
objectiveThe glycoprotein hormone erythropoietin (EPO) is required for erythropoiesis, and the kidney is the primary site of adult EPO synthesis. Limited evidence has suggested that EPO could be detectable in the brain under certain conditions, but it remains unknown if the brain might have its own EPO system for biological functions that are independent of peripheral EPO production and action. We performed this study to address this question using mice under normal conditions versus pathophysiological conditions including aging and dietary obesity.
methodsEPO expression was measured in different brain regions as well as in the cerebrospinal fluid. Hypothalamic ventricular EPO was administered to physiologically examine possible therapeutic effects on the conditions of aging and dietary obesity. Body weight, body composition, insulin tolerance, and glucose tolerance were measured to assess the central effects of EPO on metabolic physiology, and muscle strength and histology were analyzed to assess the central effects of EPO on muscle function. In addition, β2-adrenergic receptor knockout bone marrow transplant was employed to determine the potential role of bone marrow in linking the brain to some of these peripheral functions.
resultsThis study revealed that EPO is expressed in the ventromedial hypothalamus in addition to a few other brain regions and is present in the cerebrospinal fluid. Unlike blood EPO concentration, which increased with aging and dietary obesity, hypothalamic EPO decreased in these disease conditions. Therapeutically, aged mice were chronically treated with EPO in the hypothalamic ventricle, showing an increase in lean mass, while body weight and fat mass decreased as a result of a moderate reduction of food intake. Both muscle and metabolic functions were improved by this central treatment, and mechanistically, adrenergic signals to the bone marrow played a role in conveying hypothalamic EPO to these peripheral actions. Dietary obesity was also studied, showing that hypothalamic EPO treatment caused a reduction in food intake and obesity, leading to improved metabolic functions related to decreased fat as well as increased lean mass.
conclusionsHypothalamic EPO plays a role in the central regulation of muscle and metabolic physiology, while its decline contributes to aging and obesity physiology in a manner that is independent of peripheral EPO.
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