Review
Biochemistry & Molecular Biology
Panpan Liu, Zhuli Yang, Youjun Wang, Aomin Sun
Summary: The heart relies on glucose and fatty acids as major energy substrates, and their shift in preference is associated with cardiac diseases. STIM1, a calcium sensor, has been identified as a critical player in cardiac hypertrophy and diabetic cardiomyopathy, and its involvement in energy metabolism and the molecular mechanisms are not well understood. Understanding the role of STIM1 in regulating energy substrate preference could provide insights into novel therapeutic targets for cardiac metabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Baigalmaa Lkhagva, Ting-Wei Lee, Yung-Kuo Lin, Yao-Chang Chen, Cheng-Chih Chung, Satoshi Higa, Yi-Jen Chen
Summary: The article discusses the high prevalence and mortality rates of atrial fibrillation in diabetes, emphasizing the importance of understanding the pathophysiological mechanisms of atrial fibrillation and the development of new therapeutic approaches.
Article
Biochemistry & Molecular Biology
Hanna Sarah Kutsche, Rolf Schreckenberg, Klaus-Dieter Schlueter
Summary: Uncoupling proteins UCP2 and UCP3 may have multiple functions in striated muscles, including protection against mitochondria-dependent oxidative stress, transportation of pyruvate, fatty acids, and protons, and metabolic sensing. UCP2 is mainly expressed in cardiac tissues, while UCP3 dominates in skeletal muscles.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Cell Biology
Qutuba G. Karwi, Qiuyu Sun, Gary D. Lopaschuk
Summary: Diabetes increases cardiac reliance on fatty acids as the major energy source, leading to negative impacts on cardiac function and structure, efficiency, and energy status, while also making the heart more vulnerable to ischemic injury.
Review
Cardiac & Cardiovascular Systems
Xuewen Duan, Xingguang Liu, Zhenzhen Zhan
Summary: Mortality from heart diseases, especially ischemic cardiomyopathy, remains the highest in the world. While adult mammalian hearts have limited regenerative capacity, early neonatal hearts possess stronger regenerative ability. Promoting endogenous regeneration of adult mammalian cardiomyocytes is crucial for improving the prognosis of heart failure patients and finding effective therapeutic strategies. This review focuses on the role of energy metabolism in cardiac regeneration to provide insights into manipulating heart regeneration and promoting heart repair after injury.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Cell Biology
Liuyifei Huang, Yan Xing, Xiaoxuan Ning, Zhixiang Yu, Xiao Bai, Limin Liu, Shiren Sun
Summary: Abnormal lipid and glucose metabolisms are closely associated with various diseases, and finding key molecules involved in these processes is essential for treatment. This review discusses the roles and mechanisms of the transcription factor Twist1 in obesity, insulin resistance, fatty acid oxidation, and skeletal muscle glucose metabolism, providing a rational perspective for considering Twist1 as a potential treatment target.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Biochemistry & Molecular Biology
Krishnamoorthi Sumaiya, Thiruvelselvan Ponnusamy, Kalimuthusamy Natarajaseenivasan, Santhanam Shanmughapriya
Summary: The abnormal increase in cardio-metabolic diseases has led to the exploration of novel mechanisms involved in these diseases. Recent evidence reveals that the derangement of cardiac energy metabolism plays a crucial role in the development and progression of chronic cardio-metabolic diseases. miRNAs, as novel executors, regulate cardiac metabolism through base pairing with target transcripts, and several miRNAs are involved in different aspects of cardiac energy metabolism. A better understanding of these mechanisms is important for developing novel therapeutic strategies for cardiometabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Ezra B. Ketema, Gary D. Lopaschuk
Summary: Perturbations in myocardial energy substrate metabolism are key contributors to heart diseases, with post-translational acetylation-mediated modification of metabolic enzymes emerging as an important regulatory mechanism. However, the functional consequences of acetylation changes on metabolic alterations and myocardial dysfunction are not clearly defined.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Amanda A. Greenwell, Keshav Gopal, Tariq R. Altamimi, Christina T. Saed, Faqi Wang, Seyed Amirhossein Tabatabaei Dakhili, Kim L. Ho, Liyan Zhang, Farah Eaton, Jennifer Kruger, Rami Al Batran, Gary D. Lopaschuk, Gavin Y. Oudit, John R. Ussher
Summary: The study revealed impaired myocardial glucose oxidation in a mouse model of BTHS before the development of overt cardiac dysfunction, highlighting a potential pharmacological target for mitigating cardiomyopathy in BTHS.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nguyen Ngoc Trang, Ting-Wei Lee, Yu-Hsun Kao, Tze-Fan Chao, Ting- Lee, Yi-Jen Chen
Summary: The ketogenic diet may improve the condition of diabetic cardiomyopathy by suppressing fatty acid metabolism, increasing ketone utilization, and reducing endoplasmic reticulum stress and inflammation.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Fan Ying, Hao Liu, Eva Hoi Ching Tang, Ishan Lakhani, Ningning Liu, Zhengyuan Xia, Shiming Liu
Summary: EP4 deficiency in mice under high-fat diet resulted in cardiac hypertrophy and fibrosis, accompanied by reduced fatty acid uptake and inhibited ATP generation. EP4 tightly regulates the rates of cardiac fatty acid uptake and ATP generation via the FOXO1/CD36 signaling axis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Fatemeh Yarmohammadi, A. Wallace Hayes, Gholamreza Karimi
Summary: Cardiac lipotoxicity is the harmful effects of excess lipid deposition in cardiomyocytes, resulting in changes in cardiac structure and function. Dysfunction in the heart is associated with abnormal lipid metabolism, potentially causing cardiomyocyte distress and subsequent contractile dysfunction. Various compounds have been researched for their protective effects against lipotoxicity progression in the heart, involving mechanisms such as improvement of calcium homeostasis, lipid metabolism, and mitochondrial dysfunction.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Pharmacology & Pharmacy
Shubhangi Saxena, Neha Dagar, Vishwadeep Shelke, Maciej Lech, Pragyanshu Khare, Anil Bhanudas Gaikwad
Summary: The kidney undergoes metabolic reprogramming in various disease states, and understanding the involved bioenergetic pathways and developing targeted interventions are crucial for addressing the high number of kidney disease cases worldwide. Reprogramming of metabolic pathways has been observed in kidney disease, and therapies targeting these pathways have shown promising results in retarding disease progression. This review focuses on potential pharmacological interventions targeting metabolic reprogramming that have advanced through clinical trials and preclinical studies, with the aim of managing kidney disease effectively in the future.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Nguyen Ngoc Trang, Cheng-Chih Chung, Ting-Wei Lee, Wan-Li Cheng, Yu-Hsun Kao, Shih-Yu Huang, Ting- Lee, Yi-Jen Chen
Summary: Studies have shown that GLP-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors can improve myocardial function, regulate energy metabolism and apoptosis signaling pathways in diabetic cardiomyopathy, thereby reducing myocardial fibrosis and cell apoptosis. The combined treatment with these two drugs may be a potential strategy for targeting diabetic cardiomyopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tatsuya Iso, Masahiko Kurabayashi
Summary: The heart is a metabolic omnivore that mainly burns long-chain fatty acids for energy. Muscle-type continuous capillaries play a crucial role in regulating fatty acid uptake into cardiomyocytes, and impaired transport can lead to cardiac dysfunction. In cases of reduced fatty acid uptake, there is compensatory increase in glucose use, but supplementation of alternative fuels like medium-chain fatty acids and ketone bodies can partially restore contractile dysfunction caused by energy insufficiency.
Review
Biochemistry & Molecular Biology
Amanda A. Greenwell, Jadin J. Chahade, John R. Ussher
Article
Cardiac & Cardiovascular Systems
Malak Almutairi, Keshav Gopal, Amanda A. Greenwell, Adrian Young, Robert Gill, Hanin Aburasayn, Rami Al Batran, Jadin J. Chahade, Manoj Gandhi, Farah Eaton, Ryan J. Mailloux, John R. Ussher
Summary: The study demonstrates that liraglutide indirectly augments myocardial glucose oxidation, potentially contributing to improved cardiovascular outcomes in people with type 2 diabetes.
CANADIAN JOURNAL OF CARDIOLOGY
(2021)
Article
Cell Biology
Rami Al Batran, Keshav Gopal, Megan E. Capozzi, Jadin J. Chahade, Bruno Saleme, S. Amirhossein Tabatabaei-Dakhili, Amanda A. Greenwell, Jingjing Niu, Malak Almutairi, Nikole J. Byrne, Grant Masson, Ryekjang Kim, Farah Eaton, Erin E. Mulvihill, Lea Garneau, Andrea R. Masters, Zeruesenay Desta, Carlos A. Velazquez-Martinez, Celine Aguer, Peter A. Crawford, Gopinath Sutendra, Jonathan E. Campbell, Jason R. B. Dyck, John R. Ussher
Article
Cardiac & Cardiovascular Systems
Amanda A. Greenwell, Keshav Gopal, Tariq R. Altamimi, Christina T. Saed, Faqi Wang, Seyed Amirhossein Tabatabaei Dakhili, Kim L. Ho, Liyan Zhang, Farah Eaton, Jennifer Kruger, Rami Al Batran, Gary D. Lopaschuk, Gavin Y. Oudit, John R. Ussher
Summary: The study revealed impaired myocardial glucose oxidation in a mouse model of BTHS before the development of overt cardiac dysfunction, highlighting a potential pharmacological target for mitigating cardiomyopathy in BTHS.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Cell Biology
Keshav Gopal, Rami Al Batran, Tariq R. Altamimi, Amanda A. Greenwell, Christina T. Saed, Seyed Amirhossein Tabatabaei Dakhili, M. Toni E. Dimaano, Yongneng Zhang, Farah Eaton, Gopinath Sutendra, John R. Ussher
Summary: The study demonstrates that inhibition of FoxO1 improves diastolic dysfunction in diabetic cardiomyopathy by stimulating PDH activity. The interplay between FoxO1 inhibition and PDH activity plays a crucial role in improving cardiac function.
Article
Endocrinology & Metabolism
Amanda A. Greenwell, Christina T. Saed, Seyed Amirhossein Tabatabaei Dakhili, Kim L. Ho, Keshav Gopal, Jordan S. F. Chan, Oksana O. Kaczmar, Scott A. Dyer, Farah Eaton, Gary D. Lopaschuk, Rami Al Batran, John R. Ussher
Summary: Ketogenic diets did not effectively promote fat loss or improve glucose homeostasis in obese mice, while a low-fat and high-complex carbohydrate diet resulted in beneficial changes in body composition and improved glucose tolerance. Therefore, caution should be taken when considering ketogenic diets as a non-pharmacological strategy for obesity.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Hamza Mechchate, Abdualrahman Mohammed Abdualkader, James Bradshaw Bernacchi, Keshav Gopal, S. Amirhossein Tabatabaei Dakhili, Kunyan Yang, Amanda A. Greenwell, Xingxing Kong, Peter A. Crawford, Rami Al Batran
Summary: Muscle ketone body oxidation does not affect glucose and fat metabolism, but disrupts muscle BCAA catabolism and alters BCATm expression.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Cell Biology
Seyed Amirhossein Tabatabaei Dakhili, Kunyan Yang, Cassandra A. A. Locatelli, Christina T. Saed, Amanda A. Greenwell, Jordan S. F. Chan, Jadin J. Chahade, Jared Scharff, Shahad Al-Imarah, Farah Eaton, Peter A. Crawford, Keshav Gopal, Erin E. Mulvihill, John R. Ussher
Summary: Acute elevations in circulating ketones improve glucose tolerance in obesity, independent of muscle ketone oxidation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Rami Al Batran, Keshav Gopal, Hanin Aburasayn, Amina Eshreif, Malak Almutairi, Amanda A. Greenwell, Scott A. Campbell, Bruno Saleme, Emily A. Court, Farah Eaton, Peter E. Light, Gopinath Sutendra, John R. Ussher