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Human lipin 1 mutations lead to episodic rhabdomyolysis, and some affected patients exhibit cardiac abnormalities, including exercise-induced cardiac dysfunction and cardiac triglyceride accumulation. Furthermore, lipin 1 expression is deactivated in failing heart, but the effects of lipin 1 deactivation in myocardium are incompletely understood. We generated mice with cardiac-specific lipin 1 KO (cs-\n                    <jats:italic>Lpin1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) to examine the intrinsic effects of lipin 1 in the myocardium. Cs-\n                    <jats:italic>Lpin1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice had normal systolic cardiac function but mild cardiac hypertrophy. Compared with littermate control mice, PA content was higher in cs-\n                    <jats:italic>Lpin1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    hearts, which also had an unexpected increase in diacylglycerol and triglyceride content. Cs-\n                    <jats:italic>Lpin1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice exhibited diminished cardiac cardiolipin content and impaired mitochondrial respiration rates when provided with pyruvate or succinate as metabolic substrates. After transverse aortic constriction\u2013induced pressure overload, loss of lipin 1 did not exacerbate cardiac hypertrophy or dysfunction. However, loss of lipin 1 dampened the cardiac ionotropic response to dobutamine and exercise endurance in association with reduced protein kinase A signaling. These data suggest that loss of lipin 1 impairs cardiac functional reserve, likely due to effects on glycerolipid homeostasis, mitochondrial function, and protein kinase A signaling.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.134340","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T14:01:18Z","timestamp":1620568878000},"source":"Crossref","is-referenced-by-count":28,"title":["Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations"],"prefix":"10.1172","volume":"6","author":[{"given":"Kari T.","family":"Chambers","sequence":"first","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7072-5603","authenticated-orcid":true,"given":"Alison R.","family":"Swearingen","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita T.","family":"Brookheart","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla J.","family":"Weinheimer","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8763-5866","authenticated-orcid":true,"given":"Timothy R.","family":"Koves","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute and Sarah W. 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