Chong Wee Liew1, Shanshan Xu1, Xuerong Wang1, Maximilian McCann1, Hyerim Whang Kong1, Andrew C Carley1, Jingbo Pang1, Giamila Fantuzzi1, J Michael O'Donnell1, E Douglas Lewandowski2. 1. From the Department of Physiology and Biophysics (C.W.L., S.X., M.M., H.W.K., A.C.C., J.M.O., E.D.L.) and Center for Cardiovascular Research (X.W., A.C.C., J.M.O., E.D.L.), University of Illinois College of Medicine at Chicago; Department of Kinesiology and Nutrition, University of Illinois at Chicago College of Applied Health Sciences (J.P., G.F.); and Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.C.C., E.D.L.). 2. From the Department of Physiology and Biophysics (C.W.L., S.X., M.M., H.W.K., A.C.C., J.M.O., E.D.L.) and Center for Cardiovascular Research (X.W., A.C.C., J.M.O., E.D.L.), University of Illinois College of Medicine at Chicago; Department of Kinesiology and Nutrition, University of Illinois at Chicago College of Applied Health Sciences (J.P., G.F.); and Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (A.C.C., E.D.L.). dougl@sbpdiscovery.org.
Abstract
BACKGROUND: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy. METHODS AND RESULTS: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45.6%; fractional shortening, -22.6%). We report the first evidence for initially improved glucose tolerance and insulin sensitivity in response to 2 weeks transverse aortic constriction versus sham, linked to enhanced insulin signaling in liver and visceral adipose tissue (epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with upregulated oxidative/thermogenic gene expression, and downregulated lipolysis and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic constriction, the metabolic profile reversed with impaired insulin sensitivity and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and heart, and downregulation of oxidative enzymes in brown adipose tissue and oxidative and lipogenic genes in inguinal WAT. CONCLUSIONS: Changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied expression of adipose genes associated with altered insulin response/glucose handling and thermogenesis occurred prior to any functional decline in transverse aortic constriction hearts. The findings demonstrate multiphasic responses in extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning providing potential metabolic benefits.
BACKGROUND: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy. METHODS AND RESULTS: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45.6%; fractional shortening, -22.6%). We report the first evidence for initially improved glucose tolerance and insulin sensitivity in response to 2 weeks transverse aortic constriction versus sham, linked to enhanced insulin signaling in liver and visceral adipose tissue (epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with upregulated oxidative/thermogenic gene expression, and downregulated lipolysis and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic constriction, the metabolic profile reversed with impaired insulin sensitivity and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and heart, and downregulation of oxidative enzymes in brown adipose tissue and oxidative and lipogenic genes in inguinal WAT. CONCLUSIONS: Changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied expression of adipose genes associated with altered insulin response/glucose handling and thermogenesis occurred prior to any functional decline in transverse aortic constriction hearts. The findings demonstrate multiphasic responses in extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning providing potential metabolic benefits.
Authors: María Valero-Muñoz; Shanpeng Li; Richard M Wilson; Maarten Hulsmans; Tamar Aprahamian; José J Fuster; Matthias Nahrendorf; Philipp E Scherer; Flora Sam Journal: Circ Heart Fail Date: 2016-01 Impact factor: 8.790
Authors: Alexander Bartelt; Oliver T Bruns; Rudolph Reimer; Heinz Hohenberg; Harald Ittrich; Kersten Peldschus; Michael G Kaul; Ulrich I Tromsdorf; Horst Weller; Christian Waurisch; Alexander Eychmüller; Philip L S M Gordts; Franz Rinninger; Karoline Bruegelmann; Barbara Freund; Peter Nielsen; Martin Merkel; Joerg Heeren Journal: Nat Med Date: 2011-01-23 Impact factor: 53.440
Authors: Joseph R Goldenberg; Andrew N Carley; Ruiping Ji; Xiaokan Zhang; Matt Fasano; P Christian Schulze; E Douglas Lewandowski Journal: Circulation Date: 2019-03-26 Impact factor: 29.690
Authors: Marcello Panagia; Howard H Chen; Dominique Croteau; Yin-Ching Iris Chen; Chongzhao Ran; Ivan Luptak; Lee Josephson; Wilson S Colucci; David E Sosnovik Journal: Circ Cardiovasc Imaging Date: 2018-03 Impact factor: 7.792
Authors: Kamila M Bledzka; Iyad H Manaserh; Jessica Grondolsky; Jessica Pfleger; Rajika Roy; Erhe Gao; J Kurt Chuprun; Walter J Koch; Sarah M Schumacher Journal: J Mol Cell Cardiol Date: 2021-02-04 Impact factor: 5.000