Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment
Previous studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the pote...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Current Research in Physiology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665944122000050 |
| _version_ | 1811178511037104128 |
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| author | Dharendra Thapa Bingxian Xie Bellina A.S. Mushala Manling Zhang Janet R. Manning Paramesha Bugga Michael W. Stoner Michael J. Jurczak Iain Scott |
| author_facet | Dharendra Thapa Bingxian Xie Bellina A.S. Mushala Manling Zhang Janet R. Manning Paramesha Bugga Michael W. Stoner Michael J. Jurczak Iain Scott |
| author_sort | Dharendra Thapa |
| collection | DOAJ |
| description | Previous studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the potential to improve contractile function in the diabetic heart. Using an ex vivo approach, we examined whether short-term adropin treatment could enhance cardiac function in a mouse model of diet-induced obesity. Our study showed that acute adropin treatment reduces inhibitory phosphorylation of pyruvate dehydrogenase in primary neonatal cardiomyocytes, and leads to moderate improvements in ex vivo cardiac function in mice fed a low fat diet. Conversely, short-term exposure to adropin led to a small decrease in cardiac function in mice fed a long-term high fat diet. Insulin treatment did not significantly alter cardiac function in adropin treated hearts from either low or high fat diet mice, however acute adropin treatment did moderately restore some aspects of downstream insulin signaling in high fat diet fed mice. Overall, these data suggest that in an ex vivo setting, acute adropin treatment alone is not sufficient to promote improved cardiac function in obese animals. |
| first_indexed | 2024-04-11T06:20:37Z |
| format | Article |
| id | doaj.art-61011c507a704b55a8aad0c38eff5e3c |
| institution | Directory Open Access Journal |
| issn | 2665-9441 |
| language | English |
| last_indexed | 2024-04-11T06:20:37Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Physiology |
| spelling | doaj.art-61011c507a704b55a8aad0c38eff5e3c2022-12-22T04:40:36ZengElsevierCurrent Research in Physiology2665-94412022-01-0155562Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatmentDharendra Thapa0Bingxian Xie1Bellina A.S. Mushala2Manling Zhang3Janet R. Manning4Paramesha Bugga5Michael W. Stoner6Michael J. Jurczak7Iain Scott8Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USACenter for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USADivision of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA; Corresponding author. Division of Cardiology, Department of Medicine, University of Pittsburgh, BST E1259, 200 Lothrop Street, Pittsburgh, PA, 15261, USA.Previous studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the potential to improve contractile function in the diabetic heart. Using an ex vivo approach, we examined whether short-term adropin treatment could enhance cardiac function in a mouse model of diet-induced obesity. Our study showed that acute adropin treatment reduces inhibitory phosphorylation of pyruvate dehydrogenase in primary neonatal cardiomyocytes, and leads to moderate improvements in ex vivo cardiac function in mice fed a low fat diet. Conversely, short-term exposure to adropin led to a small decrease in cardiac function in mice fed a long-term high fat diet. Insulin treatment did not significantly alter cardiac function in adropin treated hearts from either low or high fat diet mice, however acute adropin treatment did moderately restore some aspects of downstream insulin signaling in high fat diet fed mice. Overall, these data suggest that in an ex vivo setting, acute adropin treatment alone is not sufficient to promote improved cardiac function in obese animals.http://www.sciencedirect.com/science/article/pii/S2665944122000050AdropinCardiac functionHigh fat dietMiceContractilityInsulin |
| spellingShingle | Dharendra Thapa Bingxian Xie Bellina A.S. Mushala Manling Zhang Janet R. Manning Paramesha Bugga Michael W. Stoner Michael J. Jurczak Iain Scott Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment Current Research in Physiology Adropin Cardiac function High fat diet Mice Contractility Insulin |
| title | Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment |
| title_full | Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment |
| title_fullStr | Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment |
| title_full_unstemmed | Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment |
| title_short | Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment |
| title_sort | diet induced obese mice are resistant to improvements in cardiac function resulting from short term adropin treatment |
| topic | Adropin Cardiac function High fat diet Mice Contractility Insulin |
| url | http://www.sciencedirect.com/science/article/pii/S2665944122000050 |
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