Modification of lung endoplasmic reticulum genes expression and NF-kB protein levels in obese ovalbumin-sensitized male and female rats

Life Sci. 2020 Apr 15:247:117446. doi: 10.1016/j.lfs.2020.117446. Epub 2020 Feb 18.

Abstract

Aims: Previous studies showed a close relationship between obesity and asthma. In this study, we investigated the expression of endoplasmic reticulum (ER) stress genes in the lung tissue of obese ovalbumin (OVA)-sensitized male and female rats.

Main methods: The rats were divided into eight groups (n = 5 per group) as follows: female and male rats fed with normal diet (FND and MND, respectively), female and male OVA-sensitized rats fed with normal diet (F-OND and M-OND, respectively), female and male rats fed with high-fat diet (F-HFD and M-HFD, respectively), female and male OVA-sensitized rats fed with high-fat diet (F-OHFD and M-OHFD, respectively). All rats were fed with a high-fat diet or standard pelts for 8 weeks, and for another 4 weeks, they were sensitized by OVA or saline. At the end of the study, lung tissue NF-kB protein level was assessed, and ER stress markers genes expression was determined by Real Time-PCR.

Key finding: OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration-response to shift to the left. In addition, the results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F-OHFD rats was statistically lower than that of the M-OHFD group (p < 0.05). Moreover, the results showed that diet-induced obesity increased the expression of ATF4, ATF6, GRP78, XBP-1, and CHOP as well as the protein level of NF-kB in this experimental model of asthma, markedly in the F-OHFD group.

Significance: The results suggest that ER stress may be involved in the pathogenesis of asthma observed in obese OVA-sensitized rats, especially in the female animals.

Keywords: Asthma; CHOP; Endoplasmic reticulum stress; GRP78; Obesity.

MeSH terms

  • Animals
  • Asthma / metabolism
  • Diet, High-Fat
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress / genetics*
  • Female
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / metabolism
  • Leptin / metabolism*
  • Lung
  • Male
  • Membrane Proteins / metabolism
  • Methacholine Chloride / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Obesity / metabolism
  • Ovalbumin / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Time Factors

Substances

  • HSP70 Heat-Shock Proteins
  • Leptin
  • Membrane Proteins
  • NF-kappa B
  • glucose-regulated proteins
  • Methacholine Chloride
  • Ovalbumin