The role of high fat diet in the regulation of MAP kinases activity in left ventricular fibrosis

Acta Histochem. 2019 Apr;121(3):303-310. doi: 10.1016/j.acthis.2019.01.010. Epub 2019 Feb 4.

Abstract

It 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) remodelling. Activation of pro-inflammatory factors such as transforming growth factor β (TGF-β) can directly stimulate mitogen-activated protein kinase (MAPK) p38 and JNK. The aim of the study was to evaluate the level of TGF-β and MAPK p38 and JNK in the LV in Sprague Dawley (SPRD) rats maintained on a high fat diet (HFD). The SPRD rats from 4 weeks of age were on a normal fat diet (NFD) or a HFD for 12 weeks (NFD-16-week-old rats, NFD 16-wk; or HFD-16-week-old rats, HFD 16-wk) or 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 (biochemical, Real Time PCR and immunohistochemical analysis). TGF-β mRNA expression did not differ between the study groups of rats. However, p38 MAPK mRNA expression was significantly lower in the HFD 20-wk rats than in both the HFD 16-wk rats and the NFD 20-wk rats. c-jun mRNA expression was significantly higher in the HFD 16-wk rats than in the NFD 16-wk rats. There was significantly lower expression of c-jun mRNA in the HFD 20-wk rats and in the NFD 20-wk rats than in the HFD 16-wk rats and in the NFD 16-wk rats, respectively. 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 results suggest that a high fat diet and in two time intervals significantly influence 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.

Keywords: High fat diet; Left ventricular fibrosis; Mitogen-activated protein kinases; Transforming growth factor β.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects*
  • Fibrosis / metabolism
  • Heart Diseases / metabolism*
  • Heart Ventricles / metabolism*
  • Male
  • Myocardium / metabolism*
  • Obesity / metabolism
  • Rats
  • Transforming Growth Factor beta / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Transforming Growth Factor beta
  • p38 Mitogen-Activated Protein Kinases