High fat and sugar diet may affect the liver- study

05/10/05 Mice that were fed diets high in fat and sugar developed immune system abnormalities in their livers, including reduced numbers of natural killer T (NKT) cells. These diet-related changes may contribute to obesity-related liver disease, according to a new study. The study is published in the October 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at interscience.wiley.com/journal/hepatology.

NKT cells originate in the thymus but accumulate in the liver where they regulate the production of cytokines (cell proteins). A previous study of leptin-deficient obese mice noted depleted levels of NKT cells. However, since obese humans have increased leptin levels, the researchers were not sure if their findings in mice were relevant to human fatty liver disease. To address this question, they studied a new diet-induced model of non-alcoholic fatty liver disease.

The researchers, led by Zhiping Li of Johns Hopkins University in Baltimore, obtained wild-type mice and fed them commercial diets with different nutritional contents for four to twelve weeks. The mice were then sacrificed to obtain liver and serum tissue. The researchers isolated hepatic mononuclear cells, which they then incubated and evaluated by flow cytometry. They also isolated total hepatic RNA for analysis. Finally, they measured levels of serum alanine aminotransferases (ALT), a marker of liver injury.

The mice on high fat diets gained significantly more weight than the mice on normal diets, and they also developed fatty livers. Their hepatic mononuclear cells revealed significantly fewer hepatic CD4+ NKT cells. Subsequent tests revealed doubled production of IL-12, a cytokine that reduces NKT cell viability, as well as increased NKT cell death.

The results also showed that high fat diets increased the production of hepatic pro-inflammatory cytokine. When the researchers induced liver injury in mice on the varying diets, they found that high fat-diet mice experienced more inflammation and necrosis than normal-diet mice.

This study shows that high-fat diets correlate to a chronic inflammatory state in the liver, which promotes chronic liver disease. The researchers suggest a potential mechanism for this outcome: diet-induced depletion of the hepatic NKT cells that balance local production of pro- and anti-inflammatory cytokines.

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