Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension
| Autor: | Uwe Tegtbur, Rudi Stinkens, Thomas Langenickel, Gijs H. Goossens, Jens Jordan, Tim Heise, Marcus May, Stefan Engeli, Bas Havekes, Sven Haufe, Ellen E. Blaak, Thomas Jax, Diego Albrecht, Parasar Pal |
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| Přispěvatelé: | Promovendi NTM, Humane Biologie, RS: NUTRIM - R2 - Liver and digestive health, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Interne Geneeskunde, MUMC+: MA Endocrinologie (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Adipose Tissue/metabolism obesity Tetrazoles Blood Pressure 030204 cardiovascular system & hematology Sacubitril Lipid Metabolism/drug effects 0302 clinical medicine lipid metabolism Exercise/physiology Aminobutyrates/administration & dosage 030212 general & internal medicine Tetrazoles/administration & dosage INTERSTITIAL ANGIOTENSIN-II Calcium Channel Blockers/administration & dosage INSULIN-RESISTANCE Aminobutyrates GLUCOSE-METABOLISM Middle Aged Calcium Channel Blockers HUMAN ADIPOCYTES Drug Combinations Editorial ADIPOSE-TISSUE Treatment Outcome Adipose Tissue Valsartan BRAIN NATRIURETIC PEPTIDE Obesity Abdominal Hypertension/diagnosis ComputingMethodologies_DOCUMENTANDTEXTPROCESSING HEART-FAILURE Female Drug Monitoring Drug Monitoring/methods medicine.drug medicine.medical_specialty TRIAL VAL-HEFT hypertension valsartan Blood Pressure/drug effects neprilysin Abdominal/diagnosis Angiotensin Receptor Antagonists 03 medical and health sciences NEPRILYSIN INHIBITION Insulin resistance Lipid oxidation Double-Blind Method Internal medicine Internal Medicine medicine Lipolysis Humans Clinical Trials Amlodipine Natriuretic Peptides sacubitril Exercise Obesity Abdominal/diagnosis NORMAL-WEIGHT exercise-induced lipolysis natriuretic peptide business.industry Amlodipine/administration & dosage Biphenyl Compounds Natriuretic Peptides/metabolism Original Articles medicine.disease natriuretic peptide neprilysin Kardiovaskuläre Luft- und Raumfahrtmedizin Blood pressure Endocrinology Angiotensin Receptor Antagonists/administration & dosage sacubitril/valsartan business Neprilysin/antagonists & inhibitors Sacubitril Valsartan |
| Zdroj: | Hypertension (Dallas, Tex. : 1979) Hypertension, 71(1), 70-77. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 0194-911X |
| DOI: | 10.1161/HYPERTENSIONAHA.117.10224 |
| Popis: | Supplemental Digital Content is available in the text. Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks’ treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130–180 mm Hg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3-2H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864. |
| Databáze: | OpenAIRE |
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