The effect of a high fat diet in the regulation of MAP kinase in left ventricle fibrosis

Abstract

IntroductionIt is well known that obesity contributes to the development of systemic inflammatory responses, which in turn may be involved in the process of interstitial fibrosis and left ventricular (LV) remodeling. Activation of proinflammatory factors such as transforming growth factor β (TGF‐β) can directly stimulate mitogen‐activated protein kinase (MAPK) p38 and JNK.PurposeThe aim of this study was to evaluate the level of TGF‐β, MAPK p38 and JNK in the LV in Sprague Dawley (SPRD) rats maintained on a high fat diet (HFD).MethodsThe SPRD rats were maintained on a normal fat diet (NFD) or on a HFD from 4 weeks of age for 12 weeks (NFD 16‐week‐old rats, NFD 16‐wk; or HFD 16‐week‐old rats, HFD 16‐wk) or for 16 weeks (NFD 20‐week‐old rats, NFD 20‐wk; or HFD 20‐week‐old rats, HFD 20‐wk). At the end of the experiment, blood and LV were collected from all rats for further analysis (Real‐Time PCR, histopathological and immunohistochemical analysis). Consent was obtained from The Local Animal Research Ethics Committee (33/2011).ResultsThe LV fibrosis area in relation to the entire LV area was significantly higher in the HFD 16‐wk rats and the HFD 20‐wk rats compared with the NFD 16‐wk rats and the NFD 20‐wk rats, respectively. TGF‐β mRNA expression did not differ between the study groups of rats. However, p38 MAPK mRNA expression and c‐jun mRNA expression were significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats. TGF‐β type II receptor (TβRII) protein demonstrated only cytoplasmic reactivity, while p38 MAPK protein and c‐jun protein showed both nuclear and cytoplasmic reactivity. The p38 MAPK nuclear reaction did not differ significantly between the study groups of rats. In contrast, the cytoplasmic response of the p38 MAPK was dependent on the administration of both HFD in two time intervals to the groups of rats. Significant differences in the nuclear reaction for c‐jun were observed between the exanimated groups of rats. The c‐jun nuclear expression was significantly lower in the HFD 20‐wk rats than in the HFD 16‐wk rats.ConclusionA high fat diet caused an increase in LV fibrosis in SPRD rats. Additionally, extension by the next 4 weeks the duration of HFD intake did not increase the LV fibrosis area. Moreover, high fat diet in both intervals significantly influences the expression of p38 MAPK and JNK in the LV. However, demonstrating their potential involvement in the processes of interstitial myocardial fibrosis and left ventricular remodeling requires further research.Support or Funding InformationThis study was financially supported by statutory funds from the Medical University of Warsaw (1MA/N/2018).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.