Abstract 19924: Circulating Factors in Stable Human HFpEF Induces “Beiging” of White Adipose Tissue In Vitro
Background: Despite the increasing prevalence of heart failure (HF) with preserved ejection fraction (HFpEF) in humans, there are no evidence-based therapies for HFpEF. Clinical studies indicate a relationship between obesity-associated dysfunctional white adipose tissue (AT) and HFpEF. We recently showed that HFpEF is associated with “beiging” in white AT, in hypertension-induced and TAC-induced HFpEF in lean mice. We now seek to investigate the translational implications of these findings.
Methods: Sera were collected from chronic, stable HFpEF patients from an ambulatory HF clinic. Patients with HFpEF were enrolled if they were previously admitted with a HFpEF exacerbation within the prior year and had a LVEF >50% within 6 months prior to enrollment. Control samples were obtained from healthy subjects without HF or known cardiac disease. Sera were used to treat visceral adipose tissue samples obtained from wild-type mice and cultured in DMEM medium for various time points (30 min, 6h and 24h). Tissue samples were then collected and used for molecular and histological assays.
Results: There was a significant increase in mRNA expression of brown markers in white AT treated with serum from HFpEF vs. control after 6h of incubation. Those markers included ucp-1, a regulator of thermogenic capability of brown fat (2.0-fold increase; p<0.05), pgc1α (3.5-fold increase; p<0.001) and prmd6 (2.5-fold increase; p<0.01). hsl mRNA expression was also increased (1.6-fold increase; p<0.01) which suggests activation of the lipolytic pathway in AT. Moreover, incubation with HFpEF serum (24h) induced white AT lipoatrophy with a decrease in adipocyte size (1066±38μm2 vs. control serum 1165±11μm2; p<0.05). p38 MAPK phosphorylation is seen in browning activation, and white AT treated with HFpEF serum (30 min) showed a significant increase in p38 phosphorylation by 9.0-fold (p<0.001) vs. control serum.
Conclusion: These findings indicate that circulating factors, such as natriuretic peptides, in chronic HFpEF may induce a “beiging” phenotype in white AT potentially by p38 activation. This may have important implications for adipose tissue function, overall metabolic homeostasis and future drug development in human HFpEF where therapy continues to be elusive.
Author Disclosures: M. Valero-Munoz: None. R.M. Wilson: None. F. Sam: None.
- © 2016 by American Heart Association, Inc.