by María Valero-Muñoz, Shanpeng Li, Richard M

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Heart Failure With Preserved Ejection Fraction Induces Beiging in Adipose TissueCLINICAL PERSPECTIVE by María Valero-Muñoz, Shanpeng Li, Richard M. Wilson, Maarten Hulsmans, Tamar Aprahamian, José J. Fuster, Matthias Nahrendorf, Philipp E. Scherer, and Flora Sam Circ Heart Fail Volume 9(1):e002724 December 31, 2015 Copyright © American Heart Association, Inc. All rights reserved.

Heart failure with preserved ejection fraction (HFpEF) induces changes in adipose tissue (AT) depots size and morphology. Heart failure with preserved ejection fraction (HFpEF) induces changes in adipose tissue (AT) depots size and morphology. A, Body composition assessed by magnetic resonance imaging, including fat and lean mass, in sham and HFpEF mice 4 wk after saline or d-aldosterone infusion (n=6–12 animals per group). B, Representative macroscopic and microscopic (hematoxylin-eosin [H&E] staining, ×20) images of epididymal white AT (eWAT; top) and inguinal WAT (iWAT; middle). Representative macroscopic and microscopic (H&E staining, ×40) images of brown AT (BAT; bottom) from sham and HFpEF mice (n=4–8 animals per group). C, Adipocyte size of eWAT and iWAT. María Valero-Muñoz et al. Circ Heart Fail. 2016;9:e002724 Copyright © American Heart Association, Inc. All rights reserved.

Quantitative reverse transcriptase polymerase chain reaction analysis of adipose depots and cold tolerance test in sham and heart failure with preserved ejection fraction (HFpEF) mice. Quantitative reverse transcriptase polymerase chain reaction analysis of adipose depots and cold tolerance test in sham and heart failure with preserved ejection fraction (HFpEF) mice. Gene expression analysis of brown (uncoupling protein 1 [ucp-1], cell death-inducing DFFA-like effector a [cidea], and epithelial V-like antigen [eva]) and white (adiponectin-apn, leptin, and resistin) adipose tissue (AT) markers in epididymal white AT (eWAT; A) and inguinal WAT (iWAT; B; n=6–12 animals per group). C, Gene expression analysis of brown adipose tissue markers (ucp-1, cidea, and eva) and metabolic enzymes (hormone-sensitive lipase [hsl], lipoprotein lipase [lpl], and fatty acid binding protein 4 [fatp4]) in brown AT (BAT; n=6–12 animals per group). D, Left, Basal body temperature before the cold tolerance test (CTT); middle, body temperature during CTT; right, loss of body weight after 4 h of CTT (n=5 animals per group). María Valero-Muñoz et al. Circ Heart Fail. 2016;9:e002724 Copyright © American Heart Association, Inc. All rights reserved.

Inflammatory markers in adipose depots of sham and heart failure with preserved ejection fraction (HFpEF) mice. Inflammatory markers in adipose depots of sham and heart failure with preserved ejection fraction (HFpEF) mice. A, Number of neutrophils, Ly6Clow macrophages, and Ly6Chigh monocytes per milligram of epididymal white adipose tissue (eWAT) and Ki67+ Ly6Clow macrophages proliferation. B, Representative flow cytometry staining of stromal vascular fraction (SVF) cells from eWAT. C, Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis of inflammatory markers in inguinal WAT (iWAT). D, qRT-PCR analysis of inflammatory markers in brown AT (BAT); n=6–12 animals per group. María Valero-Muñoz et al. Circ Heart Fail. 2016;9:e002724 Copyright © American Heart Association, Inc. All rights reserved.

Mechanisms involved in white adipose tissue (AT) phenotypic change during heart failure with preserved ejection fraction (HFpEF). Mechanisms involved in white adipose tissue (AT) phenotypic change during heart failure with preserved ejection fraction (HFpEF). Quantitative analysis and representative blots of (A) p38 total protein and p38 phosphorylation, (B) hormone-sensitive lipase (HSL) total protein expression and HSL phosphorylation, (C) β3-receptor protein, and (D) protein kinase A (PKA) total protein and PKA phosphorylation in epididymal white AT (eWAT) from sham and HFpEF mice. E, Natriuretic peptide receptor type A (npra) to natriuretic peptide receptor type C (nrpc) gene expression ratio in eWAT and (F) brown AT (BAT) from sham and HFpEF mice. G, Atrial natriuretic peptide (anp) and brain natriuretic peptide (bnp) left ventricular gene expressions in sham and HFpEF mice (n=4–14 animals per group). María Valero-Muñoz et al. Circ Heart Fail. 2016;9:e002724 Copyright © American Heart Association, Inc. All rights reserved.

Heart failure with preserved ejection fraction (HFpEF) induced by transverse aortic constriction (TAC) recapitules the findings observed in white adipose tissue (WAT) depots size and morphology. Heart failure with preserved ejection fraction (HFpEF) induced by transverse aortic constriction (TAC) recapitules the findings observed in white adipose tissue (WAT) depots size and morphology. A, Body weight and (B) WAT weight 2 wk after TAC or sham operation. C, Adipocyte size and (D) representative microscopic (hematoxylin-eosin staining, ×20) images of WAT in TAC and sham mice. E, Gene expression analysis of brown (uncoupling protein 1 [ucp-1], cell death-inducing DFFA-like effector a [cidea], and epithelial V-like antigen [eva]) and white (adiponectin-apn, leptin, and resistin) AT markers and (F) Natriuretic peptide receptor type A (npra) to natriuretic peptide receptor type C (nrpc) gene expression ratio in WAT from sham and TAC-HFpEF mice (n=4 animals per group). *P=0.05 vs sham, **P<0.05 vs sham. María Valero-Muñoz et al. Circ Heart Fail. 2016;9:e002724 Copyright © American Heart Association, Inc. All rights reserved.