title: Mechanisms underlying hypertriglyceridemia in rats with monosodium L-glutamate-induced obesity: evidence of XBP-1/PDI/MTP axis activation.
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.
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Lucas Martins
authors: LM
authors: França
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Larissa Nara Costa
authors: LN
authors: Freitas
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Vinicyus Teles
authors: VT
authors: Chagas
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Caio Fernando Ferreira
authors: CF
authors: Coêlho
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Wermerson Assunção
authors: WA
authors: Barroso
authors: Laboratory of Molecular and Cellular Pathology, Department of Pathology, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Graciomar Conceição
authors: GC
authors: Costa
authors: Laboratory of Molecular and Cellular Pathology, Department of Pathology, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil.
authors: Lucilene Amorim
authors: LA
authors: Silva
authors: Laboratory of Vascular Biology, Heart Institute, University of São Paulo, Avenida Enéas de Carvalho Aguiar, 44, 05.403-900 São Paulo, SP, Brazil.
authors: Victor
authors: V
authors: Debbas
authors: Laboratory of Vascular Biology, Heart Institute, University of São Paulo, Avenida Enéas de Carvalho Aguiar, 44, 05.403-900 São Paulo, SP, Brazil.
authors: Francisco Rafael Martins
authors: FR
authors: Laurindo
authors: Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Avenida dos Portugueses, 1966, 65.080-805 São Luís, MA, Brazil. Electronic address: marcuspaes@ufma.br.
authors: Antonio Marcus de Andrade
authors: AM
authors: Paes
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D020723:Glucuronic Acid; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000139:chemically induced; D018384:Oxidative Stress; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000138:chemical synthesis / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605545:Xbp1 protein, rat; C106092:microsomal triglyceride transfer protein; D020723:Glucuronic Acid; D019704:Protein Disulfide-Isomerases
keywords: Endoplasmic reticulum stress; Hypertriglyceridemia; MSG-induced obesity; Microsomal triglyceride transfer protein