GROWING rates of obesity have raised concerns regarding the resulting metabolic diseases caused by overeating, such as Type 2 diabetes and liver disease. In a recent study, researchers at Helmholtz Zentrum München have joined forces with the German Center for Diabetes Research (DZD) and the German Cancer Research Center (DKFZ) in an attempt to establish the effects of food deprivation on the liver.
Using transcript arrays to assess genomic makeup in relation to diet, the team observed differences in liver cell genetic activity caused by fasting. Their examination showed that the gene for the protein GADD45β, previously associated with DNA damage repair and cell cycle, varied depending on diet. In this case, its production of the molecule tended to correspond with the level of fasting; deprivation of food triggered a greater production of GADD45β.
The study also determined that GADD45β controls the absorption of fatty acids in the liver. In simulation analyses of mice, they found that those without the necessary gene were more likely to develop liver disease, whereas upon restoration of the protein the sugar metabolism and fat content of the liver normalised once again. Production of GADD45β was stimulated when fasting, which in turn regulated the metabolism and reduced fat accumulation in the liver. In a subsequent phase assessing the effect on humans the same results were achieved, to the conclusion that metabolism is adjustable through the reduction of calorie intake. Prof Stephan Herzig, Director of the Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, Neuherberg, Germany, commented that “The stress on the liver cells caused by fasting consequently appears to stimulate GADD45β production, which then adjusts the metabolism to the low food intake.”
The team are positive that their collaboration will be beneficial to the future prevention and treatment of liver disease. With further research, they hope that food deprivation might be used in a controlled manner in order to adjust the metabolism in the liver, thereby reducing the risk of liver disease and other renal complications. Prof Herzig added: “Once we understand how fasting influences our metabolism we can attempt to bring about this effect therapeutically.”
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