According to a recent study, published in the October issue of the journal Hepatology, a diet high in fat and sugar triggered immune system abnormalities, including reduced levels of NKT cells, in the livers of mice. Natural killer T (NKT) cells in the liver regulate production of cytokines, which are cell proteins. The authors said these diet-related changes may contribute to obesity -related liver disease.
The researchers found that the mice on the high-fat diet gained much more weight than mice fed a normal diet. The mice on the high-fat diet also developed fatty livers and had increased production of IL-12, a cytokine that reduces NKT cell viability, and had increased NKT cell death.
The high-fat diet also promoted production of pro-inflammatory cytokines. Upon induction of liver injury in the mice, it was found that those on the high-fat diet experienced more liver inflammation and damage than mice on the normal diet.
The study concludes on the note that high-fat diets are associated with a chronic inflammatory state in the liver, which promotes chronic liver disease. The authors said this may be the result of diet-induced depletion of NKT cells that normally balance production of pro- and anti-inflammatory cytokines.
The authors stress that further evaluation of other mouse strains, different age groups and genders will be necessary to clarify if any of these factors modulate susceptibility to diet-related changes in hepatic NKT cells. These findings are important because they clearly demonstrate significant dietary effects on classic NKT cells and cytokine production by other liver mononuclear cells.
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Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome, a cluster of metabolic abnormalities related to insulin resistance, including central obesity, dyslipidemia, hypertension, and hyperglycemia. Some patients with NAFLD have bland steatosis, and they may follow a benign clinical course. However, an unknown proportion of subjects with NAFLD have more advanced disease and a potential to progress to cirrhosis and its complications.