Ketone body 3-hydroxybutyrate elevates cardiac output through peripheral vasorelaxation and enhanced cardiac contractility

Ahmad T, Miller PE, McCullough M, Desai NR, Riello R, Psotka M, Bohm M, Allen LA, Teerlink JR, Rosano GMC, Lindenfeld J (2019) Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials. Eur J Heart Fail 21:1064–1078. https://doi.org/10.1002/ejhf.1557

Article  PubMed  Google Scholar 

Aubert G, Martin OJ, Horton JL, Lai L, Vega RB, Leone TC, Koves T, Gardell SJ, Kruger M, Hoppel CL, Lewandowski ED, Crawford PA, Muoio DM, Kelly DP (2016) The failing heart relies on ketone bodies as a fuel. Circulation 133:698–705. https://doi.org/10.1161/CIRCULATIONAHA.115.017355

Article  CAS  PubMed  PubMed Central  Google Scholar 

Batlle DC, Peces R, LaPointe MS, Ye M, Daugirdas JT (1993) Cytosolic free calcium regulation in response to acute changes in intracellular pH in vascular smooth muscle. Am J Physiol 264:C932-943. https://doi.org/10.1152/ajpcell.1993.264.4.C932

Article  CAS  PubMed  Google Scholar 

Bedi KC Jr, Snyder NW, Brandimarto J, Aziz M, Mesaros C, Worth AJ, Wang LL, Javaheri A, Blair IA, Margulies KB, Rame JE (2016) Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation 133:706–716. https://doi.org/10.1161/CIRCULATIONAHA.115.017545

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bing RJ, Siegel A, Ungar I, Gilbert M (1954) Metabolism of the human heart. Am J Med 16:504–515. https://doi.org/10.1016/0002-9343(54)90365-4

Article  CAS  PubMed  Google Scholar 

Boedtkjer E (2018) Acid-base regulation and sensing: Accelerators and brakes in metabolic regulation of cerebrovascular tone. J Cereb Blood Flow Metab 38:588–602. https://doi.org/10.1177/0271678X17733868

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Damkier HH, Aalkjaer C (2012) NHE1 knockout reduces blood pressure and arterial media/lumen ratio with no effect on resting pHi in the vascular wall. J Physiol 590:1895–1906. https://doi.org/10.1113/jphysiol.2011.227132

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boedtkjer E, Hansen KB, Boedtkjer DMB, Aalkjaer C, Boron WF (2016) Extracellular HCO3– is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ. J Cereb Blood Flow Metab 36:965–980. https://doi.org/10.1177/0271678X15610787

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Matchkov VV, Boedtkjer DM, Aalkjaer C (2016) Negative News: Cl– and HCO3– in the vascular wall. Physiology (Bethesda) 31:370–383. https://doi.org/10.1152/physiol.00001.2016

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Praetorius J, Matchkov VV, Stankevicius E, Mogensen S, Fuchtbauer AC, Simonsen U, Fuchtbauer EM, Aalkjaer C (2011) Disruption of Na+, HCO3– cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca2+ sensitivity, and hypertension development in mice. Circulation 124:1819–1829. https://doi.org/10.1161/CIRCULATIONAHA.110.015974

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Praetorius J, Aalkjaer C (2006) NBCn1 (slc4a7) mediates the Na+-dependent bicarbonate transport important for regulation of intracellular pH in mouse vascular smooth muscle cells. Circ Res 98:515–523. https://doi.org/10.1161/01.RES.0000204750.04971.76

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Aalkjaer C (2012) Intracellular pH in the resistance vasculature: regulation and functional implications. J Vasc Res 49:479–496. https://doi.org/10.1159/000341235

Article  CAS  PubMed  Google Scholar 

Boedtkjer E, Aalkjaer C (2022) The solution to bicarbonate. Am J Physiol Heart Circ Physiol 322:H685–H686. https://doi.org/10.1152/ajpheart.00057.2022

Article  CAS  PubMed  PubMed Central  Google Scholar 

Botker HE, Hausenloy D, Andreadou I, Antonucci S, Boengler K, Davidson SM, Deshwal S, Devaux Y, Di Lisa F, Di Sante M, Efentakis P, Femmino S, Garcia-Dorado D, Giricz Z, Ibanez B, Iliodromitis E, Kaludercic N, Kleinbongard P, Neuhauser M, Ovize M, Pagliaro P, Rahbek-Schmidt M, Ruiz-Meana M, Schluter KD, Schulz R, Skyschally A, Wilder C, Yellon DM, Ferdinandy P, Heusch G (2018) Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection. Basic Res Cardiol 113:39. https://doi.org/10.1007/s00395-018-0696-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Botker HE, Lassen TR, Jespersen NR (2018) Clinical translation of myocardial conditioning. Am J Physiol Heart Circ Physiol 314:H1225–H1252. https://doi.org/10.1152/ajpheart.00027.2018

Article  CAS  PubMed  Google Scholar 

Cahill GF Jr (2006) Fuel metabolism in starvation. Annu Rev Nutr 26:1–22. https://doi.org/10.1146/annurev.nutr.26.061505.111258

Article  CAS  PubMed  Google Scholar 

Cahill GF Jr, Herrera MG, Morgan AP, Soeldner JS, Steinke J, Levy PL, Reichard GA Jr, Kipnis DM (1966) Hormone-fuel interrelationships during fasting. J Clin Invest 45:1751–1769. https://doi.org/10.1172/JCI105481

Article  CAS  PubMed  PubMed Central  Google Scholar 

Conrad N, Judge A, Tran J, Mohseni H, Hedgecott D, Crespillo AP, Allison M, Hemingway H, Cleland JG, McMurray JJV, Rahimi K (2018) Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. Lancet 391:572–580. https://doi.org/10.1016/S0140-6736(17)32520-5

Article  PubMed  PubMed Central  Google Scholar 

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K (2016) Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab 24:256–268. https://doi.org/10.1016/j.cmet.2016.07.010

Article  CAS  PubMed  Google Scholar 

Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R, Mari A, Pieber TR, Muscelli E (2016) Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes 65:1190–1195. https://doi.org/10.2337/db15-1356

Article  CAS  PubMed  Google Scholar 

Gaskell WH (1880) On the Tonicity of the Heart and Blood Vessels. J Physiol 3:48–92. https://doi.org/10.1113/jphysiol.1880.sp000083

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gopalasingam N, Christensen KH, Berg Hansen K, Nielsen R, Johannsen M, Gormsen LC, Boedtkjer E, Norregaard R, Moller N, Wiggers H (2023) Stimulation of the hydroxycarboxylic acid receptor 2 with the ketone body 3-hydroxybutyrate and niacin in patients with chronic heart failure: Hemodynamic and metabolic effects. J Am Heart Assoc 12:e029849. https://doi.org/10.1161/JAHA.123.029849

Article  PubMed  PubMed Central  Google Scholar 

Gormsen LC, Svart M, Thomsen HH, Sondergaard E, Vendelbo MH, Christensen N, Tolbod LP, Harms HJ, Nielsen R, Wiggers H, Jessen N, Hansen J, Botker HE, Moller N (2017) Ketone body infusion with 3-hydroxybutyrate reduces myocardial glucose uptake and increases blood flow in humans: A positron emission tomography study. J Am Heart Assoc 6:e005066. https://doi.org/10.1161/JAHA.116.005066

Article  PubMed  PubMed Central  Google Scholar 

Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447:619–628. https://doi.org/10.1007/s00424-003-1067-2

Article  CAS  PubMed  Google Scholar 

Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343(Pt 2):281–299

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hansen KB, Staehr C, Rohde PD, Homilius C, Kim S, Nyegaard M, Matchkov VV, Boedtkjer E (2020) PTPRG is an ischemia risk locus essential for HCO3–-dependent regulation of endothelial function and tissue perfusion. Elife 9:e57553. https://doi.org/10.7554/eLife.57553

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heggermont WA, Papageorgiou AP, Heymans S, van Bilsen M (2016) Metabolic support for the heart: complementary therapy for heart failure? Eur J Heart Fail 18:1420–1429. https://doi.org/10.1002/ejhf.678

Article  PubMed  Google Scholar 

Horton JL, Davidson MT, Kurishima C, Vega RB, Powers JC, Matsuura TR, Petucci C, Lewandowski ED, Crawford PA, Muoio DM, Recchia FA, Kelly DP (2019) The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight 4:e124079. https://doi.org/10.1172/jci.insight.124079

Article  PubMed  PubMed Central  Google Scholar 

Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW (2017) GPCR-mediated signaling of metabolites. Cell Metab 25:777–796. https://doi.org/10.1016/j.cmet.2017.03.008

Article  CAS  PubMed  Google Scholar 

Jacobus WE, Pores IH, Lucas SK, Weisfeldt ML, Flaherty JT (1982) Intracellular acidosis and contractility in the normal and ischemic heart as examined by 31P NMR. J Mol Cell Cardiol 14(3):13–20. https://doi.org/10.1016/0022-2828(82)90124-9

Article  CAS  PubMed  Google Scholar 

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