Cell Reports (Aug 2024)
Growth differentiation factor 15 alleviates diastolic dysfunction in mice with experimental diabetic cardiomyopathy
- Jordan S.F. Chan,
- Seyed Amirhossein Tabatabaei Dakhili,
- Maria Areli Lorenzana-Carrillo,
- Keshav Gopal,
- Serena M. Pulente,
- Amanda A. Greenwell,
- Kunyan Yang,
- Christina T. Saed,
- Magnus J. Stenlund,
- Sally R. Ferrari,
- Indiresh A. Mangra-Bala,
- Tanin Shafaati,
- Rakesh K. Bhat,
- Farah Eaton,
- Michael Overduin,
- Sebastian Beck Jørgensen,
- Gregory R. Steinberg,
- Erin E. Mulvihill,
- Gopinath Sutendra,
- John R. Ussher
Affiliations
- Jordan S.F. Chan
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Seyed Amirhossein Tabatabaei Dakhili
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Maria Areli Lorenzana-Carrillo
- Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada; Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G3, Canada
- Keshav Gopal
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Serena M. Pulente
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada
- Amanda A. Greenwell
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Kunyan Yang
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Christina T. Saed
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Magnus J. Stenlund
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Sally R. Ferrari
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Indiresh A. Mangra-Bala
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Tanin Shafaati
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Rakesh K. Bhat
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
- Farah Eaton
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada
- Michael Overduin
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
- Sebastian Beck Jørgensen
- Bio Innovation Hub Transformational Research Unit, Novo Nordisk, Boston, MA 02142, USA
- Gregory R. Steinberg
- Centre for Metabolism, Obesity, Diabetes Research, McMaster University, Hamilton, ON L8S 4K1, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada
- Erin E. Mulvihill
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada
- Gopinath Sutendra
- Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada; Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2G3, Canada
- John R. Ussher
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 8
p. 114573
Abstract
Summary: Growth differentiation factor 15 (GDF15) is a peptide with utility in obesity, as it decreases appetite and promotes weight loss. Because obesity increases the risk for type 2 diabetes (T2D) and cardiovascular disease, it is imperative to understand the cardiovascular actions of GDF15, especially since elevated GDF15 levels are an established biomarker for heart failure. As weight loss should be encouraged in the early stages of obesity-related prediabetes/T2D, where diabetic cardiomyopathy is often present, we assessed whether treatment with GDF15 influences its pathology. We observed that GDF15 treatment alleviates diastolic dysfunction in mice with T2D independent of weight loss. This cardioprotection was associated with a reduction in cardiac inflammation, which was likely mediated via indirect actions, as direct treatment of adult mouse cardiomyocytes and differentiated THP-1 human macrophages with GDF15 failed to alleviate lipopolysaccharide-induced inflammation. Therapeutic manipulation of GDF15 action may thus have utility for both obesity and diabetic cardiomyopathy.
