Financiado en parte por Amgen, Eli Lilly and Company, AstraZeneca, Sanofi, Bayer HealthCare, Vifor Pharma, Janssen Pharmaceuticals
Sustained alternate-day fasting potentiates doxorubicin cardiotoxicity
Ozcan M, Guo Z, Valenzuela Ripoll C, Diab A, Picataggi A, Rawnsley D, Lotfinaghsh A, Bergom C, Szymanski J, Hwang D, Asnani A, Kosiborod M, Zheng J, Hayashi RJ, Woodard PK, Kovacs A, Margulies KB, Schilling J, Razani B, Diwan A, Javaheri A
Cell metabolism · 85 citas
Etiquetas de revisión
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Gobierno
- U.S. Department of Veterans Affairs
- Organización sin fines de lucro
- American Heart Association
- Empresa
- Amgen
- Empresa
- Eli Lilly and Company
- Empresa
- AstraZeneca
- Empresa
- Sanofi
- Universidad u hospital
- Washington University in St. Louis
- Universidad u hospital
- Children's Discovery Institute
- Organización sin fines de lucro
- Hope Center for Neurological Disorders
- Universidad u hospital
- St. Louis Children's Hospital
- Empresa
- Bayer HealthCare
- Empresa
- Vifor Pharma
- Gobierno
- National Institutes of Health
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of Diabetes and Digestive and Kidney Diseases
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Empresa
- Janssen Pharmaceuticals
- Gobierno
- NIH
- Gobierno
- NHLBI NIH HHS
- Gobierno
- BLRD VA
- Gobierno
- NIDDK NIH HHS
- Gobierno
- NINDS NIH HHS
- Universidad u hospital
- St. Louis Children's Hospital
- Gobierno
- NHLBI
- Gobierno
- NIH HHS
- Universidad u hospital
- Washington University in Saint Louis Children's Discovery Institute
- Subvenciones
- National Heart, Lung, and Blood Institute (K08 HL163469); U.S. Department of Veterans Affairs (HL107594); National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK056341); National Heart, Lung, and Blood Institute (R01HL159461); American Heart Association (898679); U.S. Department of Veterans Affairs (I01BX004235); U.S. Department of Veterans Affairs (I01BX005981); National Institutes of Health (1s10od028597-01); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020579); U.S. Department of Veterans Affairs (R01HL147884); National Heart, Lung, and Blood Institute (K08 HL138262); National Heart, Lung, and Blood Institute (R01HL147884); National Heart, Lung, and Blood Institute (HL143431); U.S. Department of Veterans Affairs (MC-II-2020-893); National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK052574-); National Heart, Lung, and Blood Institute (R01 HL155344); National Institute of Neurological Disorders and Stroke (R01 NS094692); U.S. Department of Veterans Affairs (I01 BX003415); U.S. Department of Veterans Affairs (HL143431); Children's Discovery Institute (MC-FR-2020-919); U.S. Department of Veterans Affairs (P30DK052574); U.S. Department of Veterans Affairs (NS094692); National Heart, Lung, and Blood Institute (R01 HL125838); National Heart, Lung, and Blood Institute (R01 HL143431); Washington University in St. Louis (P30 DK052574); National Heart, Lung, and Blood Institute (1R01HL155344); National Heart, Lung, and Blood Institute (R01 HL107594); National Heart, Lung, and Blood Institute (K08HL145019); National Institutes of Health (P30-DK020579); National Institutes of Health (K08-HL145019); National Institutes of Health (P30DK056341); National Institutes of Health (P30 DK052574); National Institutes of Health (HL107594); National Institutes of Health (R01HL147884); National Institutes of Health (NS094692); National Heart, Lung, and Blood Institute (HL107594); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK131188)
Según 26 financiadores declarados.
Publicación
- Publicado
- 2023-03-02 · Cell Metab · vol. 35 · número 6 · págs. 928–942.e4
- Editorial
- Cell Press
- Citado
- 101 citas · más que el 100% de estudios similares · 18.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 41 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC-ND
- Áreas de investigación
- GDF15 and Related Biomarkers · Nutrition and Health in Aging · Cancer-related cognitive impairment studies
- Palabras clave
- TFEB, Cardiotoxicity, Doxorubicin, Autophagy, Heart failure, Medicine, Internal medicine, Endocrinology, Cancer research, Biology, Chemotherapy, Apoptosis, Biochemistry
- MeSH
- lysosomes, myocytes, cardiac, animals, humans, mice, doxorubicin, fasting, autophagy, basic helix-loop-helix leucine zipper transcription factors, heart failure, cardiotoxicity
21 autores
- Mualla Özcan🇺🇸Washington University in St. Louis
- Zhen Guo🇺🇸Washington University in St. Louis
- Carla Valenzuela Ripoll🇺🇸Washington University in St. Louis
- Ahmed Diab🇺🇸Washington University in St. Louis
- Antonino Picataggi🇺🇸Washington University in St. Louis
- David R. Rawnsley🇺🇸Washington University in St. Louis
- Aynaz Lotfinaghsh🇺🇸Washington University in St. Louis
- Carmen R. Bergom🇺🇸Washington University in St. Louis
- Jeffrey J. Szymanski🇺🇸Washington University in St. Louis
- Daniel H. Hwang🇺🇸Washington University in St. Louis
- Aarti H. Asnani🇺🇸Harvard University; Beth Israel Deaconess Hospital
- Mikhail Kosiborod🇺🇸Saint Luke's Health System
- Jie Zheng🇺🇸Washington University in St. Louis
- Robert James Hayashi🇺🇸Washington University in St. Louis
- Pamela K. Woodard🇺🇸Washington University in St. Louis
- Attila D Kovács🇺🇸Washington University in St. Louis
- Kenneth B. Margulies🇺🇸University of Pennsylvania
- Joel D. Schilling🇺🇸Washington University in St. Louis
- Babak Razani🇺🇸Washington University in St. Louis; John Cochran VA Medical Center
- Abhinav Diwan🇺🇸Washington University in St. Louis; John Cochran VA Medical Center
- Ali Javaheri🇺🇸 · autor de correspondenciaWashington University in St. Louis
Resumen
El texto original del estudio, en el idioma en que se publicó.
Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic TFEB overexpression increased growth differentiation factor 15 (GDF15) and caused heart failure and death. Cardiomyocyte TFEB knockout attenuated doxorubicin cardiotoxicity, while recombinant GDF15 was sufficient to cause cardiac atrophy. Our studies identify that both sustained alternate-day fasting and a TFEB/GDF15 pathway exacerbate doxorubicin cardiotoxicity.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).
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