Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats: A novel model of endoplasmic reticulum stress

Saet Byol Kang, Hyun Min Kim, Hyung Jun Kim, Hannah Seok, Ji Hye Huh, byungwan lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The proteins found in cow milk have been reported to cause systemic inflammation. Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders including insulin resistance and non-alcoholic fatty liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is still controversial. This is why we want to investigate in this study whether casein, which is the major protein in cow's milk, induces ER stress in the liver and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague-Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily subcutaneous injections of 1 mL 10% casein; (3) daily subcutaneous injection of 1mL 10% casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food intake, glucose and lipid parameters, and serum AST/ALT levels were measured after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed, and a TUNEL analysis was also performed. After 6 weeks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased both the gene and protein expression of ER stress markers in the liver and also caused hepatocyte apoptosis. Rosiglitazone treatment attenuated caseininduced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. In conclusion, our results may provide further insight into the effects of casein on chronic inflammatory diseases, and to have a better understanding of the mechanism of the anti-inflammatory properties of rosiglitazone regardless of its hypoglycemic effect.

Original languageEnglish
Pages (from-to)1231-1240
Number of pages10
JournalEndocrine Journal
Volume60
Issue number11
DOIs
Publication statusPublished - 2013 Dec 3

Fingerprint

rosiglitazone
Endoplasmic Reticulum Stress
Caseins
Sprague Dawley Rats
Liver
Subcutaneous Injections
Inflammation
Milk
Apoptosis
Thiazolidinediones
Injections
Proteins
In Situ Nick-End Labeling
Hypoglycemic Agents
Insulin Resistance
Weight Loss
Real-Time Polymerase Chain Reaction
Hepatocytes
Chronic Disease
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Kang, Saet Byol ; Kim, Hyun Min ; Kim, Hyung Jun ; Seok, Hannah ; Huh, Ji Hye ; lee, byungwan ; Kang, Eun Seok ; Lee, Hyun Chul ; Cha, Bong Soo. / Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats : A novel model of endoplasmic reticulum stress. In: Endocrine Journal. 2013 ; Vol. 60, No. 11. pp. 1231-1240.
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abstract = "The proteins found in cow milk have been reported to cause systemic inflammation. Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders including insulin resistance and non-alcoholic fatty liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is still controversial. This is why we want to investigate in this study whether casein, which is the major protein in cow's milk, induces ER stress in the liver and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague-Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily subcutaneous injections of 1 mL 10{\%} casein; (3) daily subcutaneous injection of 1mL 10{\%} casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food intake, glucose and lipid parameters, and serum AST/ALT levels were measured after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed, and a TUNEL analysis was also performed. After 6 weeks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased both the gene and protein expression of ER stress markers in the liver and also caused hepatocyte apoptosis. Rosiglitazone treatment attenuated caseininduced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. In conclusion, our results may provide further insight into the effects of casein on chronic inflammatory diseases, and to have a better understanding of the mechanism of the anti-inflammatory properties of rosiglitazone regardless of its hypoglycemic effect.",
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Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in Sprague-Dawley rats : A novel model of endoplasmic reticulum stress. / Kang, Saet Byol; Kim, Hyun Min; Kim, Hyung Jun; Seok, Hannah; Huh, Ji Hye; lee, byungwan; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo.

In: Endocrine Journal, Vol. 60, No. 11, 03.12.2013, p. 1231-1240.

Research output: Contribution to journalArticle

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AU - Kang, Saet Byol

AU - Kim, Hyun Min

AU - Kim, Hyung Jun

AU - Seok, Hannah

AU - Huh, Ji Hye

AU - lee, byungwan

AU - Kang, Eun Seok

AU - Lee, Hyun Chul

AU - Cha, Bong Soo

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AB - The proteins found in cow milk have been reported to cause systemic inflammation. Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders including insulin resistance and non-alcoholic fatty liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is still controversial. This is why we want to investigate in this study whether casein, which is the major protein in cow's milk, induces ER stress in the liver and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague-Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily subcutaneous injections of 1 mL 10% casein; (3) daily subcutaneous injection of 1mL 10% casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food intake, glucose and lipid parameters, and serum AST/ALT levels were measured after an overnight fast. Real time RT-PCR and immunohistochemical staining for various ER stress markers were performed, and a TUNEL analysis was also performed. After 6 weeks, casein injection induced weight reduction, systemic inflammation, and hepatic dysfunction in SD rats. Casein injection increased both the gene and protein expression of ER stress markers in the liver and also caused hepatocyte apoptosis. Rosiglitazone treatment attenuated caseininduced systemic inflammation, ER stress, deteriorated liver function, and increased apoptosis. In conclusion, our results may provide further insight into the effects of casein on chronic inflammatory diseases, and to have a better understanding of the mechanism of the anti-inflammatory properties of rosiglitazone regardless of its hypoglycemic effect.

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