Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate-induced obesity: evidence of XBP-1/PDI/MTP axis activation

Biochem Biophys Res Commun. 2014 Jan 10;443(2):725-30. doi: 10.1016/j.bbrc.2013.12.042. Epub 2013 Dec 12.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is intimately associated with insulin resistance and hypertriglyceridemia, whereas many of the mechanisms underlying this association are still poorly understood. In the present study, we investigated the relationship between microsomal triglyceride transfer protein (MTP) and markers of endoplasmic reticulum (ER) stress in the liver of rats subjected to neonatal monosodium L-glutamate (MSG)-induced obesity. At age 120 days old, the MSG-obese animals exhibited hyperglycemia, hypertriglyceridemia, insulin resistance, and liver steatosis, while the control (CTR) group did not. Analysis using fast protein liquid chromatography of the serum lipoproteins revealed that the triacylglycerol content of the very low-density lipoprotein (VLDL) particles was twice as high in the MSG animals compared with the CTR animals. The expression of ER stress markers, GRP76 and GRP94, was increased in the MSG rats, promoting a higher expression of X-box binding protein 1 (XBP-1), protein disulfide isomerase (PDI), and MTP. As the XBP-1/PDI/MTP axis has been suggested to represent a significant lipogenic mechanism in the liver response to ER stress, our data indicate that hypertriglyceridemia and liver steatosis occurring in the MSG rats are associated with increased MTP expression.

Keywords: Endoplasmic reticulum stress; Hypertriglyceridemia; MSG-induced obesity; Microsomal triglyceride transfer protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / chemical synthesis
  • DNA-Binding Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Fatty Liver / chemically induced
  • Fatty Liver / metabolism*
  • Glucuronic Acid
  • Hypertriglyceridemia / chemically induced
  • Hypertriglyceridemia / metabolism*
  • Male
  • Obesity / chemically induced
  • Oxidative Stress
  • Protein Disulfide-Isomerases / metabolism*
  • Rats
  • Rats, Wistar
  • Regulatory Factor X Transcription Factors
  • Signal Transduction
  • Transcription Factors / chemical synthesis
  • Transcription Factors / metabolism*
  • X-Box Binding Protein 1

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, rat
  • microsomal triglyceride transfer protein
  • Glucuronic Acid
  • Protein Disulfide-Isomerases