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Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences
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New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress

1
I Clinica Medica, Department of Clinical, Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy
2
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(9), 2762; https://doi.org/10.3390/nu12092762
Received: 10 August 2020 / Revised: 1 September 2020 / Accepted: 7 September 2020 / Published: 10 September 2020
(This article belongs to the Special Issue The Role of Diet in Fatty Liver Disease)
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The intricate NAFLD pathogenesis is summarized by the multiple-hits hypothesis, which combines all the environmental and genetic factors that promote the development of NAFLD into a single scenario. Among these, bacterial lipopolysaccharides (LPS) are derived from the overgrowth of Gram-negative bacteria and translocated mainly as a consequence of enhanced intestinal permeability. Furthermore, oxidative stress is increased in NAFLD as a consequence of reactive oxygen species (ROS) overproduction and a shortage of endogenous antioxidant molecules, and it is promoted by the interaction between LPS and the Toll-like receptor 4 system. Interestingly, oxidative stress, which has previously been described as being overexpressed in cardiovascular disease, could represent the link between LPS and the increased cardiovascular risk in NAFLD subjects. To date, the only effective strategy for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH) is the loss of at least 5% body weight in overweight and/or obese subjects. However, the dose-dependent effects of multispecies probiotic supplementation on the serum LPS level and cardiometabolic profile in obese postmenopausal women were demonstrated. In addition, many antibiotics have regulatory effects on intestinal microbiota and were able to reduce serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor alpha (TNF-α) in NASH animal models. Regarding the oxidant status, a Mediterranean diet has been reported to reduce oxidant stress, while vitamin E at high daily dosages induced the resolution of NASH in 36% of treated patients. Silymarin had the positive effect of reducing transaminase levels in NAFLD patients and long-term treatment may also decrease fibrosis and slow liver disease progression in NASH. Finally, the influence of nutraceuticals on gut microbiota and oxidant stress in NAFLD patients has not yet been well elucidated and there are insufficient data either to support or refuse their use in these subjects. View Full-Text
Keywords: non-alcoholic fatty liver disease; lipopolysaccharide; oxidative stress; cardiovascular risk non-alcoholic fatty liver disease; lipopolysaccharide; oxidative stress; cardiovascular risk
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Ferro, D.; Baratta, F.; Pastori, D.; Cocomello, N.; Colantoni, A.; Angelico, F.; Del Ben, M. New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress. Nutrients 2020, 12, 2762.

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