Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Jul;295(1):E10-6.
doi: 10.1152/ajpendo.00011.2008. Epub 2008 Mar 18.

Alcohol and lipid metabolism

Affiliations
Review

Alcohol and lipid metabolism

Margaret Sozio et al. Am J Physiol Endocrinol Metab. 2008 Jul.

Abstract

Many new mechanisms for alcoholic steatosis have been suggested by work reported in the last five years. These include alterations of transcriptional controls of lipid metabolism, better understanding of the effects of abnormal methionine metabolism on the endoplasmic reticulum stress response, unraveling of the basis for sensitization of the Kupffer cell to lipopolysaccharide, a better understanding of the role of cytokines and adipokines in alcoholic liver disease, and implication of the innate immune and complement systems in responses to alcohol. Much of this work has been facilitated by work with knockout mice. Undoubtedly, there are interrelationships among these various pathogenic mechanisms that ultimately will provide a more cohesive picture of how heavy alcohol use deranges hepatic lipid metabolism.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Interactions between ethanol, transcriptional controls of lipid metabolism, and endoplasmic reticulum (ER) stress in the liver. PPARα, peroxisome proliferator-activated receptor-α; MTP, microsomal triglyceride transfer protein; AMPK, AMP-activated protein kinase; SREBP-1, sterol response element-binding protein-1; ACC, acetyl-CoA carboxylase. Consumption of ethanol inhibits regulatory systems that are needed to promote the oxidation of fatty acids (PPARα and AMPK) and activates the systems that stimulate fatty acid synthesis (SREBP-1, in part via activation of the ER stress response). The ER stress response also increases the likelihood that hepatocytes will undergo apoptosis.
Fig. 2.
Fig. 2.
Effects of ethanol consumption on cytokine synthesis by Kupffer cells. LPS, lipopolysaccharide; LBP, LPS-binding protein; TLR-4, toll-like receptor 4; CD14, cellular determinant 14; adipoR2, adiponectin receptor 2; ROS, reactive oxygen species; IL-6, interleukin 6; TNF-α, tumor necrosis factor-α; ERK1/2, extracellular signal-regulated kinase-1/2; Egr-1, early-growth response factor 1. Ethanol consumption increases absorption of LPS from the GI tract into the portal vein. Kupffer cells are sensitized to LPS as a result of increased expression of TLR-4 and increased levels of transcription factor Egr-1, leading to secretion of increased amounts of TNF-α and other cytokines such as IL-6. Adiponectin can counteract these effects, but circulating levels of adiponectin are reduced with heavy ethanol intake.

References

    1. Adachi Y, Bradford BU, Gao W, Bojes HK, Thurman RG. Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology 20: 453–460, 1994. - PubMed
    1. Al-Khalili L, Bouzakri K, Glund S, Lonnqvist F, Koistinen HA, Krook A. Signaling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle. Mol Endocrinol 20: 3364–3375, 2006. - PubMed
    1. Alessi MC, Bastelica D, Mavri A, Morange P, Berthet B, Grino M, Juhan-Vague I. Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol 23: 1262–1268, 2003. - PubMed
    1. Ameen C, Edvardsson U, Ljungberg A, Asp L, Akerblad P, Tuneld A, Olofsson SO, Linden D, Oscarsson J. Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver. J Biol Chem 280: 1224–1229, 2005. - PubMed
    1. Banerjee A, Apte UM, Smith R, Ramaiah SK. Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease. J Pathol 208: 473–485, 2006. - PubMed

Publication types