Researchers report possible therapeutic approach to fatty liver disease

(Medical Xpress)—Steatosis is a condition in which the body fails to properly synthesize or eliminate triglyceride fat, causing abnormal retention of lipids inside cells. Steatohepatitis, then, is liver disease characterized by inflammation and fat accumulation. The condition is typically seen in alcoholics, but it is often observed in people with diabetes and obesity. Ultimately, steatohepatits can progress to life-threatening cirrhosis.

Given the exponential rise of diabetes in developed countries, steatosis and steatohepatitis are subjects of tremendous interest to medical researchers. A new study, published in the Proceedings of the National Academy of Sciences, reports that treatment with fibroblast growth factor 1 (FGF1) is an important factor in adipose remodeling processes—mice deficient in FGF1 displayed a severe diabetic phenotype and increased inflammation and fibrosis in fatty tissues.

FGF1 is a protein encoded by the FGF1 gene. It encourages cell division and expresses a number of potent cell survival traits; this family of proteins is involved in a great number of functions including cell growth, embryonic development and tissue repair. In the current study, the researchers studied two different lines of mice: leptin-deficient mice, which develop steatosis through excessive eating; and mice with a dietary choline deficiency, which develop steatosis as a result of a defect in the way fat is broken down in the liver.

They found that FGF1 had dramatic antisteatotic effects in the leptin-deficient mice. Additionally, in these mice, FGF1 suppressed liver inflammation—hepatic steatosis can often develop into dangerous steatohepatitis characterized by serious inflammation. However, the antisteatotic effects observed in these mice were completely absent in the choline-deficient mice.

Choline deficiency causes steatosis in the absence of metabolic disease such as diabetes or obesity; the researchers conclude that the antisteatotic effects of FGF1 are dependent on catabolic pathways that are defective in the choline-deficient mice. The differences between the lines were also indicated by the zonal distribution of lipids in the animals' livers; lipid zoning is an important activity for segregating different metabolic pathways in the liver.

The study also concludes that FGF1 suppresses liver inflammation completely independently of its effects on fatty liver disease. "Our results show that rFGF1 effectively suppresses hepatic inflammation both in [leptin-deficient] mice and choline-deficient mice, as indicated by significant reductions in the expression of… proinflammatory M1 markers," the authors write.

And although the researchers thought there was potential for the treatment to produce such adverse effects as fibrosis and proliferation, these were not observed.

These results are important because no pharmacological treatments have been approved for steatohepatitis, and there are drawbacks to the existing approaches of insulin sensitizers and antioxidative treatments. By contrast, the study findings conclude that FGF1 improved hyperglycemia, insulin sensitivity and steatosis symptoms in the obese mice, though not the choline deficient line. "Our findings indicate that, in addition to its potent glucose-lowering and insulin-sensitizing effects, rFGF1 could be therapeutically effective in the treatment of non-alcoholic fatty liver disease," the authors write.