Cellular and Molecular Mechanisms Underlying the Pathogenesis of Fat Accumulation and Disease Progression in NAFLD

Dear Colleagues,

Among the different metabolic tasks, a leading role in liver metabolism is covered by mechanisms involved in fat storage and disposal. A derangement at any point of this complex machinery could lead to NAFLD, the most common liver disease worldwide widespread. In recent years, increasing evidence has accumulated on the different molecular mechanisms involved in NAFLD pathogenesis and in the progression from simple steatosis to steato-hepatitis and fibrosis and, eventually, cancer. A number of genetic risk factors for NAFLD/NASH susceptibility and progression have been individuated and other are currently under investigation (e.g. PNPLA3, TM6SF2, etc…). Furthermore, hepatic gene expression profile analysis has been found useful in distinguishing individuals with a different outcome in the spectrum of NAFLD severity. In recent years, a novel field called epigenetics reveals changes in gene expression unrelated to modifications to the underlying DNA sequence and linked to NAFLD. DNA methylation and non-coding RNA are found to be a major determinant of disease progression and further studies are needed to corroborate their pathogenetic and prognostic role. The liver fat accumulation is also caused by distant organ dysfunction. Recently the gut-liver axis was found to play an important role in liver inflammation and NAFLD progression. Gut microbiome composition, bacterial products (metabolome), and an alteration of gut mucosal barrier (the so-called “leaky gut”) were linked to inflammation and fibrosis in NAFLD. Finally, evidence regarding the deregulation of pathways that control de novo lipogenesis and fat catabolism, including the lipophagy pathway, is gaining increasing attention, as well as the clinical relevance of a reduction in the activity of several lipases, key enzymes for the disposal of intracellular fat. In this Special Issue of Cells, I invite you to contribute original research articles, reviews, or shorter perspective articles on all aspects related to the theme of “Cellular and Molecular Mechanisms underlying the Pathogenesis of fat accumulation and disease progression in NAFLD”. Expert articles describing mechanistic, functional, cellular, biochemical, or general aspects of NAFLD are highly welcome. Relevant topics include but are not limited to:

-NASH/NAFLD

-genetics-epigenetics

-gut-liver axis

-microbiome-metabolome

-lipid metabolism-inflammation

-lipophagy

-In vitro and in vivo models

Dr. Simone Carotti
Dr. Annamaria Altomare
Dr. Maria Francesconi
Dr. Francesco Valentini
Dr. Umberto Vespasiani-Gentilucci
Guest Editors

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• Non-alcoholic fatty liver disease/Non-alcoholic statohepatitis
• genetics
• epigenetics
• gut-liver axis
• microbiome
• metabolome
• lipid metabolism
• inflammation
• lipophagy
• In vitro and in vivo models