Cellular and molecular mechanisms of the profibrogenic effect of leptin in the liver. [ 2003 - 2004 ]

Research Grant

Researchers: Isabelle Leclercq (Principal investigator) ,  Prof Geoffrey Farrell

Brief description Cirrhosis of the liver in the 7th leading cause of death. Regardless of the underlying cause of liver injury (virus, alcohol, or in affluent countries non-alcoholic steatohepatitis -NASH), the liver repairs damage by forming scar tissue in a pocess similar to wound healing. All chronic liver diseases are associated with repeated rounds of wound-healing leading inevitably to progressive fibrosis and cirrhosis of the liver. Obesity, in addition to being linked to type II diabetes and cardiovascular diseases, is an independent risk factor for liver injury. It is the clinical setting for NASH, the most common liver disorder in western countries. Also the severity of hepatic fibrosis and the risk of progression to fibrosis in most forms of liver diseases (regardless of their cause) are dramatically increased in overweight (>60%) and obese (20% of adult Australian) patients. Leptin is an hormone that primarily controls food intake and energy balance in the body. In addition, leptin has many other functions. It is a modulator of the immune and inflammatory system, it is involved in skin wound healing and increases sclerosis in the kidney. We recently showed that leptin is necessary for fibrosis to develop in the liver and that increased levels of leptin increases the severity of liver fibrosis. It appears that leptin is a fundamental player in the biological processes of hepatic fibrosis. As increased serum levels of leptin is a feature of obesity, leptin is likely to be the missing link between obesity and increased hepatic fibrosis. By understanding the mechanisms by which leptin acts on liver cells to increase fibrosis, this work will lead to new strategies to prevent fibrosis in obese patients and to reverse scarring in the liver. With the endemic obesification in developed countries, prevention and treatment of obesity-associated liver disease will be the main challenge for the hepatologist in the next decades.

Funding Amount $AUD 166,500.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant