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Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.

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Τίτλος: Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.
Συγγραφείς: Hall JE; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Clinical and Translational Research, University of Mississippi Medical Center, Jackson, MS, U.S.A., Omoto ACM; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A., do Carmo JM; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A., da Silva AA; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A., Mouton AJ; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A., Wang Z; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A., Hall ME; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Mississippi Center for Clinical and Translational Research, University of Mississippi Medical Center, Jackson, MS, U.S.A.; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Πηγή: Clinical science (London, England : 1979) [Clin Sci (Lond)] 2026 Jul 15; Vol. 140 (7), pp. 1473-1496.
Τύπος έκδοσης: Journal Article; Review; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE
Imprint Name(s): Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society
Original Publication: London, Medical Research Society.
Ιατρικοί όροι (MeSH): Leptin*/metabolism , Brain*/metabolism , Receptor, Melanocortin, Type 4*/metabolism , Adipocytes*/metabolism , Melanocortins*/metabolism, Receptors, Leptin/metabolism ; Obesity/metabolism ; Obesity/physiopathology ; Sympathetic Nervous System/physiopathology ; Sympathetic Nervous System/metabolism ; Humans ; Animals ; Signal Transduction
Περίληψη: Tonic activation of central nervous system (CNS) leptin receptors (LepRs) and melanocortin 4 receptors (MC4Rs) is critical for maintaining normal cardiometabolic function. Deficiency of CNS LepR or MC4R signaling causes severe obesity and is accompanied by multiple metabolic abnormalities including insulin resistance, glucose intolerance, and hyperlipidemia that are only partially explained by obesity. Defective LepR and MC4R signaling also causes dysfunction of the sympathetic nervous system (SNS) and blood pressure (BP) regulation. Hyperleptinemia and activation of the CNS melanocortin system in obesity are important compensatory mechanisms that attenuate abnormalities of glucose and lipid metabolism but may also contribute to SNS activation and increased BP. Despite potentially adverse effects of increases in SNS activity and BP, pharmacological activation of brain LepRs and MC4Rs may provide an important therapeutic approach for protecting target organs, such as the heart, kidneys, and brain, from ischemic injury by improving mitochondrial function and ATP production. However, additional preclinical studies are needed to address mechanistic questions before clinical studies are begun to test the effectiveness of leptin and MC4R agonists for treating people with ischemic injury of target organs.
(© 2026 The Author(s).)
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Grant Information: R01 HL163076 United States HL NHLBI NIH HHS; R01HL181254 R01HL166737 R01HL163076 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); 25CDA1451524 American Heart Association (AHA); GM149404 GM115428 HHS | NIH | National Institute of General Medical Sciences (NIGMS); R01DK121411 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); P30 GM149404 United States GM NIGMS NIH HHS
Contributed Indexing: Keywords: acute kidney injury; diabetes mellitus; heart failure; hypertension; obesity; sympathetic nervous system
Substance Nomenclature: 0 (Leptin)
0 (Receptor, Melanocortin, Type 4)
0 (Receptors, Leptin)
0 (Melanocortins)
Entry Date(s): Date Created: 20260624 Date Completed: 20260624 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13305822
DOI: 10.1042/CS20250039
PMID: 42340064
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1470-8736
DOI:10.1042/CS20250039