Visceral Adipose Tissue Promotes Pressure-Induced Heart Failure Associated with Circulating Fatty Acids

Background: Visceral adipose tissue (VAT) is the main source of circulating fatty acids (FAs) that provides the energy substrate for the heart. Till now, studies have not shown a clear association between individual circulating FAs and heart failure (HF). In this study, we aimed to investigate the changes in circulating FAs in HF mice and their association with VAT by removing epididymal white adipose tissue (eWAT). Methods: Male C57BL/6J mice were divided into normal control and eWAT excision groups. Each group was then divided into sham group and HF group. The transverse aortic constriction (TAC) was used to induce pressure-mediated cardiac failure. HE staining and Masson’ staining were used to observe cardiac morphology. Echocardiography was used to determine diastolic left ventricular posterior wall (LVPWd), diastolic left ventricular internal diameter (LVIDd) and fractional shortening (FS%). RT-PCR was used to determine mRNA expression of atrial natriuretic peptide ( ANP ), brain natriuretic peptide ( BNP ), MYH7 , CTGF , collagen 1 ( COL1 ), COL3A1 in heart tissue of mice. HPLC measurement was used to determine serum level of FAs. Results: Cardiac enlargement and fibrosis were observed after TAC surgery evidenced by increased LVPWd, LVIDd, and increased mRNA expression of ANP, BNP, MYH7, CTGF, COL1, COL3A1 in heart tissue (P<0.05). Among various FAs species, serum arachidic acid (P<0.001), behenic acid (P<0.001), lignoceric acid (P<0.01), and docosapentaenoic acid (P<0.05) levels in HF mice were significantly decreased versus sham group. However, above mentioned four serum fatty acids were significantly decreased in both sham and HF group with eWAT excision compared with eWAT reserved. In addition, the changes accompanied by LVPWd significantly decreased and FS% significantly increased. Conclusion: Serum arachidic acid, behenic acid, lignoceric acid, and docosapentaenoic acid levels were significantly decreased in pressure-induced HF mice, most importantly, VAT excision alleviated TAC-induced cardiac failure by decreasing these four kinds of fatty acids levels.