Louisa C Howard1, Chia-Ying Liu1, Julia B Purdy1, Peter Walter1, David A Bluemke1, Colleen Hadigan1. 1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (L.C.H., C.H.), Radiology and Imaging Sciences, Clinical Center (C.-Y.L., D.A.B.), Critical Care Medicine Department (J.B.P.), and National Institute of Diabetes and Digestive and Kidney Diseases (P.W.), National Institutes of Health, Bethesda Maryland 20892.
Abstract
CONTEXT: Individuals with HIV have an elevated risk for developing cardiovascular disease compared to controls, particularly in relationship to abnormal deposition of lipid within various body compartments. Dysregulation of lipolysis may contribute to abnormal deposition of lipid in non-adipose tissues such as the heart, leading to untoward health consequences. OBJECTIVE: To evaluate potential relationships between rates of whole-body lipolysis and intramyocardial lipid content in HIV-infected subjects compared to healthy controls. DESIGN: Cross-sectional study. SETTING: National Institutes of Health Clinical Research Center in Bethesda, Maryland. PARTICIPANTS: Forty-six HIV-infected adults and 12 controls without known cardiovascular disease. MAIN OUTCOME MEASURE: Intramyocardial lipid content quantified by MRI and rates of lipolysis determined using stable isotope tracer techniques. RESULTS: We observed a significant positive correlation between the rate of appearance of glycerol and intramyocardial lipid overall (r = 0.323; P = .014) and among the HIV group separately (r = 0.361; P = .014). Multivariate regression analyses including HIV, lipid-lowering therapy, and diabetes identified both rate of appearance of glycerol and age as independent significant predictors of intramyocardial lipid (P = .01 and P = .03, respectively), but these were not significant with inclusion of visceral adipose in the analyses. CONCLUSIONS: To our knowledge, this study is among the first in humans to characterize the relationship between lipid deposition in the myocardium and direct measurement of whole-body fatty acid metabolism. Our current findings contribute to the growing understanding of factors that promote myocardial steatosis, such as visceral adiposity, and implicate lipolysis as a potential target for interventions to optimize myocardial health.
CONTEXT: Individuals with HIV have an elevated risk for developing cardiovascular disease compared to controls, particularly in relationship to abnormal deposition of lipid within various body compartments. Dysregulation of lipolysis may contribute to abnormal deposition of lipid in non-adipose tissues such as the heart, leading to untoward health consequences. OBJECTIVE: To evaluate potential relationships between rates of whole-body lipolysis and intramyocardial lipid content in HIV-infected subjects compared to healthy controls. DESIGN: Cross-sectional study. SETTING: National Institutes of Health Clinical Research Center in Bethesda, Maryland. PARTICIPANTS: Forty-six HIV-infected adults and 12 controls without known cardiovascular disease. MAIN OUTCOME MEASURE: Intramyocardial lipid content quantified by MRI and rates of lipolysis determined using stable isotope tracer techniques. RESULTS: We observed a significant positive correlation between the rate of appearance of glycerol and intramyocardial lipid overall (r = 0.323; P = .014) and among the HIV group separately (r = 0.361; P = .014). Multivariate regression analyses including HIV, lipid-lowering therapy, and diabetes identified both rate of appearance of glycerol and age as independent significant predictors of intramyocardial lipid (P = .01 and P = .03, respectively), but these were not significant with inclusion of visceral adipose in the analyses. CONCLUSIONS: To our knowledge, this study is among the first in humans to characterize the relationship between lipid deposition in the myocardium and direct measurement of whole-body fatty acid metabolism. Our current findings contribute to the growing understanding of factors that promote myocardial steatosis, such as visceral adiposity, and implicate lipolysis as a potential target for interventions to optimize myocardial health.
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