Effects of angiotensin receptor-neprilysin inhibitor on ketone body metabolism in pre-heart failure/heart failure patients.
Angiotensin receptor-neprilysin inhibitor (ARNI)
Heart failure
Ketone body
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
received:
02
03
2024
accepted:
12
07
2024
medline:
18
7
2024
pubmed:
18
7
2024
entrez:
17
7
2024
Statut:
epublish
Résumé
Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] μmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients.
Identifiants
pubmed: 39020009
doi: 10.1038/s41598-024-67524-6
pii: 10.1038/s41598-024-67524-6
doi:
Substances chimiques
Ketone Bodies
0
Angiotensin Receptor Antagonists
0
Neprilysin
EC 3.4.24.11
Angiotensin-Converting Enzyme Inhibitors
0
Valsartan
80M03YXJ7I
Fatty Acids, Nonesterified
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16493Subventions
Organisme : the JSPS KAKENHI
ID : JP24K11300
Organisme : the JSPS KAKENHI
ID : JP23K07563
Organisme : the JSPS KAKENHI
ID : JP22K08113
Informations de copyright
© 2024. The Author(s).
Références
Yurista, S. R. et al. Therapeutic potential of ketone bodies for patients with cardiovascular disease: JACC state-of-the-art review. J. Am. Coll. Cardiol. 77, 1660–1669. https://doi.org/10.1016/j.jacc.2020.12.065 (2021).
doi: 10.1016/j.jacc.2020.12.065
pubmed: 33637354
Arima, Y. The impact of ketone body metabolism on mitochondrial function and cardiovascular diseases. J. Atheroscler. Thromb. https://doi.org/10.5551/jat.RV22011 (2023).
doi: 10.5551/jat.RV22011
pubmed: 37793811
pmcid: 10999719
Ferrannini, E., Mark, M. & Mayoux, E. CV protection in the EMPA-REG OUTCOME trial: A “thrifty substrate” hypothesis. Diabetes Care 39, 1108–1114. https://doi.org/10.2337/dc16-0330 (2016).
doi: 10.2337/dc16-0330
pubmed: 27289126
Bedi, K. C. Jr. et al. 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 (2016).
doi: 10.1161/circulationaha.115.017545
pubmed: 26819374
pmcid: 4779339
Aubert, G. et al. The failing heart relies on ketone bodies as a fuel. Circulation 133, 698–705. https://doi.org/10.1161/circulationaha.115.017355 (2016).
doi: 10.1161/circulationaha.115.017355
pubmed: 26819376
pmcid: 4766035
Ho, K. L. et al. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc. Res. 115, 1606–1616. https://doi.org/10.1093/cvr/cvz045 (2019).
doi: 10.1093/cvr/cvz045
pubmed: 30778524
pmcid: 6704391
Mizuno, Y. et al. The diabetic heart utilizes ketone bodies as an energy source. Metab. Clin. Exp. 77, 65–72. https://doi.org/10.1016/j.metabol.2017.08.005 (2017).
doi: 10.1016/j.metabol.2017.08.005
pubmed: 29132539
Uchihashi, M. et al. Cardiac-specific Bdh1 overexpression ameliorates oxidative stress and cardiac remodeling in pressure overload-induced heart failure. Circ. Heart Fail. 10, e004417. https://doi.org/10.1161/circheartfailure.117.004417 (2017).
doi: 10.1161/circheartfailure.117.004417
pubmed: 29242353
Deng, Y. et al. Targeting mitochondria-inflammation circuit by β-hydroxybutyrate mitigates HFpEF. Circ. Res. 128, 232–245. https://doi.org/10.1161/circresaha.120.317933 (2021).
doi: 10.1161/circresaha.120.317933
pubmed: 33176578
Arima, Y. et al. Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation. Nat. Metab. 3, 196–210. https://doi.org/10.1038/s42255-021-00342-6 (2021).
doi: 10.1038/s42255-021-00342-6
pubmed: 33619377
McMurray, J. J. et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N. Engl. J. Med. 371, 993–1004. https://doi.org/10.1056/NEJMoa1409077 (2014).
doi: 10.1056/NEJMoa1409077
pubmed: 25176015
Januzzi, J. L. Jr. et al. Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA 322, 1085–1095. https://doi.org/10.1001/jama.2019.12821 (2019).
doi: 10.1001/jama.2019.12821
pubmed: 31475295
pmcid: 6724151
Martens, P. et al. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin. Res. Cardiol. 108, 1074–1082. https://doi.org/10.1007/s00392-019-01440-y (2019).
doi: 10.1007/s00392-019-01440-y
pubmed: 30788621
Miyashita, K. et al. Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity. Diabetes 58, 2880–2892. https://doi.org/10.2337/db09-0393 (2009).
doi: 10.2337/db09-0393
pubmed: 19690065
pmcid: 2780866
Bordicchia, M. et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J. Clin. Investig. 122, 1022–1036. https://doi.org/10.1172/jci59701 (2012).
doi: 10.1172/jci59701
pubmed: 22307324
pmcid: 3287224
Kimura, H. et al. Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo. Sci. Rep. 11, 17466. https://doi.org/10.1038/s41598-021-96970-9 (2021).
doi: 10.1038/s41598-021-96970-9
pubmed: 34465848
pmcid: 8408225
Kimura, H. et al. The thermogenic actions of natriuretic peptide in brown adipocytes: The direct measurement of the intracellular temperature using a fluorescent thermoprobe. Sci. Rep. 7, 12978. https://doi.org/10.1038/s41598-017-13563-1 (2017).
doi: 10.1038/s41598-017-13563-1
pubmed: 29021616
pmcid: 5636787
Seferovic, J. P. et al. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: A post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 5, 333–340. https://doi.org/10.1016/s2213-8587(17)30087-6 (2017).
doi: 10.1016/s2213-8587(17)30087-6
pubmed: 28330649
pmcid: 5534167
Wijkman, M. O. et al. Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: The PARAGON-HF and PARADIGM-HF trials. Cardiovasc. Diabetol. 21, 110. https://doi.org/10.1186/s12933-022-01545-1 (2022).
doi: 10.1186/s12933-022-01545-1
pubmed: 35717169
pmcid: 9206286
Kashiwagi, Y. et al. Effects of angiotensin receptor-neprilysin inhibitor on insulin resistance in patients with heart failure. ESC Heart Fail. 10, 1860–1870. https://doi.org/10.1002/ehf2.14352 (2023).
doi: 10.1002/ehf2.14352
pubmed: 36942494
pmcid: 10192229
Puchalska, P. & Crawford, P. A. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab. 25, 262–284. https://doi.org/10.1016/j.cmet.2016.12.022 (2017).
doi: 10.1016/j.cmet.2016.12.022
pubmed: 28178565
pmcid: 5313038
Carper, D. et al. Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non-shivering thermogenesis. Cell Rep. 32, 108075. https://doi.org/10.1016/j.celrep.2020.108075 (2020).
doi: 10.1016/j.celrep.2020.108075
Lommi, J. et al. Blood ketone bodies in congestive heart failure. J. Am. Coll. Cardiol. 28, 665–672. https://doi.org/10.1016/0735-1097(96)00214-8 (1996).
doi: 10.1016/0735-1097(96)00214-8
pubmed: 8772754
Kashiwagi, Y. et al. Close linkage between blood total ketone body levels and B-type natriuretic peptide levels in patients with cardiovascular disorders. Sci. Rep. 11, 6498. https://doi.org/10.1038/s41598-021-86126-0 (2021).
doi: 10.1038/s41598-021-86126-0
pubmed: 33753839
pmcid: 7985483
Lafontan, M. et al. Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol. Metab. TEM 19, 130–137. https://doi.org/10.1016/j.tem.2007.11.006 (2008).
doi: 10.1016/j.tem.2007.11.006
pubmed: 18337116
Szabó, T. et al. Increased catabolic activity in adipose tissue of patients with chronic heart failure. Eur. J. Heart Fail. 15, 1131–1137. https://doi.org/10.1093/eurjhf/hft067 (2013).
doi: 10.1093/eurjhf/hft067
pubmed: 23696611
Doehner, W., Frenneaux, M. & Anker, S. D. Metabolic impairment in heart failure: The myocardial and systemic perspective. J. Am. Coll. Cardiol. 64, 1388–1400. https://doi.org/10.1016/j.jacc.2014.04.083 (2014).
doi: 10.1016/j.jacc.2014.04.083
pubmed: 25257642
McGarry, J. D. & Foster, D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu. Rev. Biochem. 49, 395–420. https://doi.org/10.1146/annurev.bi.49.070180.002143 (1980).
doi: 10.1146/annurev.bi.49.070180.002143
pubmed: 6157353
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R. & Abel, E. D. Cardiac energy metabolism in heart failure. Circ. Res. 128, 1487–1513. https://doi.org/10.1161/circresaha.121.318241 (2021).
doi: 10.1161/circresaha.121.318241
pubmed: 33983836
pmcid: 8136750
Wang, T. J. et al. Impact of obesity on plasma natriuretic peptide levels. Circulation 109, 594–600. https://doi.org/10.1161/01.Cir.0000112582.16683.Ea (2004).
doi: 10.1161/01.Cir.0000112582.16683.Ea
pubmed: 14769680
Inoue, Y. et al. The impact of an inverse correlation between plasma B-type natriuretic peptide levels and insulin resistance on the diabetic condition in patients with heart failure. Metab. Clin. Exp. 65, 38–47. https://doi.org/10.1016/j.metabol.2015.09.019 (2016).
doi: 10.1016/j.metabol.2015.09.019
pubmed: 26892514
Oi, Y. et al. Exogenous ANP treatment ameliorates myocardial insulin resistance and protects against ischemia-reperfusion injury in diet-induced obesity. Int. J. Mol. Sci. 23, 8373. https://doi.org/10.3390/ijms23158373 (2022).
doi: 10.3390/ijms23158373
pubmed: 35955507
pmcid: 9369294
Ibrahim, N. E. et al. Effect of neprilysin inhibition on various natriuretic peptide assays. J. Am. Coll. Cardiol. 73, 1273–1284. https://doi.org/10.1016/j.jacc.2018.12.063 (2019).
doi: 10.1016/j.jacc.2018.12.063
pubmed: 30898202
Lundåsen, T. et al. PPARalpha is a key regulator of hepatic FGF21. Biochem. Biophys. Res. Commun. 360, 437–440. https://doi.org/10.1016/j.bbrc.2007.06.068 (2007).
doi: 10.1016/j.bbrc.2007.06.068
pubmed: 17601491
Badman, M. K. et al. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 5, 426–437. https://doi.org/10.1016/j.cmet.2007.05.002 (2007).
doi: 10.1016/j.cmet.2007.05.002
pubmed: 17550778
Grabacka, M., Pierzchalska, M., Dean, M. & Reiss, K. Regulation of ketone body metabolism and the role of PPARα. Int. J. Mol. Sci. 17, 2093. https://doi.org/10.3390/ijms17122093 (2016).
doi: 10.3390/ijms17122093
pubmed: 27983603
pmcid: 5187893
Raza-Iqbal, S. et al. Transcriptome analysis of K-877 (a novel selective PPARα modulator (SPPARMα))-regulated genes in primary human hepatocytes and the mouse liver. J. Atheroscler. Thromb. 22, 754–772. https://doi.org/10.5551/jat.28720 (2015).
doi: 10.5551/jat.28720
pubmed: 26040752