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Abundance of dopamine and its receptors in the brain and adipose tissue following diet-induced obesity or caloric restriction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.ORCID iD: 0009-0006-4330-5674
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.ORCID iD: 0000-0002-0964-6700
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.ORCID iD: 0000-0003-1270-2221
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2025 (English)In: Translational Research: The Journal of Laboratory and Clinical Medicine, ISSN 1931-5244, E-ISSN 1878-1810, Vol. 280, p. 41-54Article in journal (Refereed) Published
Abstract [en]

While obesity and type 2 diabetes (T2D) are associated with altered dopaminergic activity in the central nervous system and in adipose tissue (AT), the directions and underlying mechanisms remain inconclusive. Therefore, we characterized changes in the abundance of dopamine, its metabolites, and receptors DRD1 and DRD2 in the brain and AT upon dietary intervention or obesity. Male Wistar rats were fed either a standard pellet diet, a cafeteria diet inducing obesity and insulin resistance, or a calorie-restricted diet for 12 weeks. Abundance of dopamine and its receptors DRD1 and DRD2 were examined in brain regions relevant for feeding behavior and energy homeostasis. Furthermore, DRD1 and DRD2 protein levels were analyzed in rat inguinal and epidydimal AT and in human subcutaneous and omental AT from individuals with or without obesity. Rats with diet-induced obesity displayed higher dopamine levels, as well as DRD1 or DRD2 receptor levels in the caudate putamen and the nucleus accumbens core. Surprisingly, caloric restriction induced similar changes in DRD1 and DRD2, but not in dopamine levels, in the brain. Both diets reduced DRD1 abundance in inguinal and epidydimal AT, but upregulated DRD2 levels in inguinal AT. Furthermore, in human obesity, DRD1 protein levels were elevated only in omental AT, while DRD2 was upregulated in both omental and subcutaneous AT. These findings highlight dopaminergic responses to changes in energy balance, occurring both in the brain and AT. We propose that dopaminergic pathways are involved in tissue crosstalk during the development of obesity and T2D.

Place, publisher, year, edition, pages
Elsevier, 2025. Vol. 280, p. 41-54
Keywords [en]
Dopamine, Dopamine receptors, Obesity, Adipose tissue, Brain, Caloric restriction
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-557733DOI: 10.1016/j.trsl.2025.05.001ISI: 001493185500001PubMedID: 40345434Scopus ID: 2-s2.0-105004880921OAI: oai:DiVA.org:uu-557733DiVA, id: diva2:1963530
Funder
Swedish Foundation for Strategic ResearchEU, Horizon 2020, PAS GRAS 101080329Swedish Research CouncilAvailable from: 2025-06-03 Created: 2025-06-03 Last updated: 2025-06-03Bibliographically approved

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Hukema, Fleur W.Hetty, SusanneKagios, ChristakisZelleroth, SofiaFanni, GiovanniPereira, Maria J.Svensson, Maria K.Sundbom, MagnusNilsson, AnnaAndrén, Per E.Roman, ErikaEriksson, Jan W.

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Hukema, Fleur W.Hetty, SusanneKagios, ChristakisZelleroth, SofiaFanni, GiovanniPereira, Maria J.Svensson, Maria K.Sundbom, MagnusNilsson, AnnaAndrén, Per E.Roman, ErikaEriksson, Jan W.
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Clinical diabetology and metabolismDepartment of Pharmaceutical BiosciencesRenal MedicineUppsala Clinical Research Center (UCR)Upper Abdominal Surgery
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Translational Research: The Journal of Laboratory and Clinical Medicine
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