Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in Diabetic db/db Mice.

Autor:	Tarkhnishvili A; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Koentges C; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Pfeil K; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Gollmer J; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Byrne NJ; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Vosko I; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Lueg J; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Vogelbacher L; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Birkle S; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Tang S; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Bon-Nawul Mwinyella T; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany., Hoffmann MM; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Institute for Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Germany., Odening KE; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Translational Cardiology, Department of Cardiology, Bern University Hospital, Bern, Switzerland., Michel NA; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Wolf D; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Stachon P; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Hilgendorf I; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Wallner M; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Ljubojevic-Holzer S; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.; BioTechMed Graz, Graz, Austria., von Lewinski D; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Rainer P; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Sedej S; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Sourij H; Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria., Bode C; Heart Center Freiburg University, Department of Cardiology and Angiology I, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Zirlik A; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bugger H; Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Journal of lipid and atherosclerosis [J Lipid Atheroscler] 2022 May; Vol. 11 (2), pp. 161-177. Date of Electronic Publication: 2022 Mar 31.
DOI:	10.12997/jla.2022.11.2.161
Abstrakt:	Objective: Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice. Methods: A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions. Results: Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment. Conclusion: AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice. Competing Interests: Conflict of Interest: H.B. is an editor of Journal of Lipid and Atherosclerosis; however, he was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported. The authors have no conflicts of interest to declare. (Copyright © 2022 The Korean Society of Lipid and Atherosclerosis.)
Databáze:	MEDLINE
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