Systems biology applied to non-alcoholic fatty liver disease (NAFLD): treatment selection based on the mechanism of action of nutraceuticals
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Non-alcoholic fatty liver disease (NAFLD) comprises several liver pathologic states and affects 10%–35% of the population. However, the only known “treatment” for NAFLD is significant weight loss through a lifestyle change, so there is a great need for improvement in the pharmacological management of the disease. As nutraceuticals may alleviate the results of lack of treatment during the first, asymptomatic phase of the disease, we used SIMScells (www.simscells.com) and the Therapeutic Performance Mapping System (TPMS), a proprietary systems biology technology of Anaxomics (www.anaxomics. com), to predict the best nutraceuticals to use against NAFLD. We first performed a reprofiling analysis, which led us to identify 33 potential nutraceuticals that could ameliorate the illness. Next, we found the most probable mechanism of action (MoA) of four selected nutraceuticals. Some of these MoAs feature links that have never before been related to the studied pathophysiological mechanisms, thus providing new testable hypotheses. In addition, the MoAs provide two means of treatment selection, according to disease pathophysiological pathways (“motives”) or to each patient’s response to the nutraceuticals (“cluster MoAs”). In conclusion, we use TPMS to predict the molecular mechanistic explanation of the action of the current top nutraceutical used against NAFLD, L-carnitine, highlighting different response subpopulations. We also mechanistically propose the stratification of patients and usefulness of other nutraceuticals (calcitriol and thiamine) on a par or over L-carnitine according to patients’ pathophysiology.
Keywordsmechanism of action NAFLD nutraceuticals patient stratification systems biology TPMS
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