Autophagy in Non-Alcoholic Fatty Liver Disease (NAFLD)

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. The potential role of autophagy in disease is increasingly recognised and investigated. To date, a key role of autophagy in hepatic lipid metabolism is recognised and dysfunctional autophagy might be an underlying cause of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the exact role of autophagy in lipid metabolism remains controversial, with both a lipolytic function of autophagy and lipogenic function reported. This chapter aims to review the current knowledge on autophagy in NAFLD, with a special focus on its role in hepatic lipid metabolism, hepatic glucose metabolism and insulin resistance, steatohepatitis, hepatocellular injury and hepatic fibrogenesis. Finally, interaction with another cellular homeostatic process, the unfolded protein response (UPR), will be briefly discussed

The Differential Roles of T Cells in Non-alcoholic Fatty Liver Disease and Obesity

Non-alcoholic fatty liver disease (NAFLD) constitutes a spectrum of disease states characterized by hepatic steatosis and is closely associated to obesity and the metabolic syndrome. In non-alcoholic steatohepatitis (NASH), additionally, inflammatory changes and hepatocellular damage are present, representing a more severe condition, for which the treatment is an unmet medical need. Pathophysiologically, the immune system is one of the main drivers of NAFLD progression and other obesity-related comorbidities, and both the innate and adaptive immune system are involved. T cells form the cellular component of the adaptive immune system and consist of multiple differentially active subsets, i.e., T helper (Th) cells, regulatory T (Treg) cells, and cytotoxic T (Tc) cells, as well as several innate T-cell subsets. This review focuses on the role of these T-cell subsets in the pathogenesis of NAFLD, as well as the association with obesity and type 2 diabetes mellitus, reviewing the available evidence from both animal and human studies. Briefly, Th1, Th2, Th17, and Th22 cells seem to have an attenuating effect on adiposity. Th2, Th22, and Treg cells seem to decrease insulin resistance, whereas Th1, Th17, and Tc cells have an aggravating effect. Concerning NAFLD, both Th22 and Treg cells appear to have an overall tempering effect, whereas Th17 and Tc cells seem to induce more liver damage and fibrosis progression. The evidence regarding the role of the innate T-cell subsets is more controversial and warrants further exploration