Tags

Type your tag names separated by a space and hit enter

MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes.
J Hepatol. 2008 Sep; 49(3):407-16.JH

Abstract

BACKGROUND/AIMS

In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis.

METHODS

C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched controls.

RESULTS

MCD feeding increased serum ALT levels and induced hepatic steatosis, lobular inflammation and ballooning degeneration of hepatocytes, irrespective of dietary fat content. Hepatic triglyceride accumulation was similar between high and low-fat MCD-fed mice, but lipoperoxide levels were approximately 3-fold higher in the high-fat MCD-fed animals. Serum adiponectin levels increased in MCD-fed mice, although to a lesser extent in high-fat fed animals. AMPK phosphorylation was correspondingly increased in muscle of MCD-fed mice, but hepatic AMPK phosphorylation decreased, and there was little evidence of PPAR alpha activation, suggesting impaired adiponectin action in the livers of MCD-fed animals. Hepatocyte PPAR gamma mRNA levels increased in MCD-fed mice, and were associated with increased aP2 expression, indicating adipogenic transformation of hepatocytes.

CONCLUSIONS

Increased dietary lipid intake did not alter steatohepatitis severity in MCD-fed mice despite increased lipoperoxide accumulation. Instead, steatohepatitis was associated with impaired hepatic adiponectin action, and adipogenic transformation of hepatocytes in both low and high-fat MCD-fed mice.

Authors+Show Affiliations

ANU Medical School, Australian National University at The Canberra Hospital, Canberra, ACT, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18534710

Citation

Larter, Claire Z., et al. "MCD-induced Steatohepatitis Is Associated With Hepatic Adiponectin Resistance and Adipogenic Transformation of Hepatocytes." Journal of Hepatology, vol. 49, no. 3, 2008, pp. 407-16.
Larter CZ, Yeh MM, Williams J, et al. MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes. J Hepatol. 2008;49(3):407-16.
Larter, C. Z., Yeh, M. M., Williams, J., Bell-Anderson, K. S., & Farrell, G. C. (2008). MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes. Journal of Hepatology, 49(3), 407-16. https://doi.org/10.1016/j.jhep.2008.03.026
Larter CZ, et al. MCD-induced Steatohepatitis Is Associated With Hepatic Adiponectin Resistance and Adipogenic Transformation of Hepatocytes. J Hepatol. 2008;49(3):407-16. PubMed PMID: 18534710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes. AU - Larter,Claire Z, AU - Yeh,Matthew M, AU - Williams,Jacqueline, AU - Bell-Anderson,Kim S, AU - Farrell,Geoffrey C, Y1 - 2008/04/30/ PY - 2008/01/18/received PY - 2008/02/26/revised PY - 2008/03/19/accepted PY - 2008/6/7/pubmed PY - 2008/12/17/medline PY - 2008/6/7/entrez SP - 407 EP - 16 JF - Journal of hepatology JO - J. Hepatol. VL - 49 IS - 3 N2 - BACKGROUND/AIMS: In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. METHODS: C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched controls. RESULTS: MCD feeding increased serum ALT levels and induced hepatic steatosis, lobular inflammation and ballooning degeneration of hepatocytes, irrespective of dietary fat content. Hepatic triglyceride accumulation was similar between high and low-fat MCD-fed mice, but lipoperoxide levels were approximately 3-fold higher in the high-fat MCD-fed animals. Serum adiponectin levels increased in MCD-fed mice, although to a lesser extent in high-fat fed animals. AMPK phosphorylation was correspondingly increased in muscle of MCD-fed mice, but hepatic AMPK phosphorylation decreased, and there was little evidence of PPAR alpha activation, suggesting impaired adiponectin action in the livers of MCD-fed animals. Hepatocyte PPAR gamma mRNA levels increased in MCD-fed mice, and were associated with increased aP2 expression, indicating adipogenic transformation of hepatocytes. CONCLUSIONS: Increased dietary lipid intake did not alter steatohepatitis severity in MCD-fed mice despite increased lipoperoxide accumulation. Instead, steatohepatitis was associated with impaired hepatic adiponectin action, and adipogenic transformation of hepatocytes in both low and high-fat MCD-fed mice. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/18534710/MCD_induced_steatohepatitis_is_associated_with_hepatic_adiponectin_resistance_and_adipogenic_transformation_of_hepatocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(08)00280-8 DB - PRIME DP - Unbound Medicine ER -