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Abstract Details
Linking nutrient sensing, mitochondrial function, and PRR immune cell signaling in liver disease
Trends Immunol. 2022 Oct 1;S1471-4906(22)00183-1. doi: 10.1016/j.it.2022.09.002.Online ahead of print.
1Complement and Inflammation Research Section (CIRS), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: Claudia.kemper@nih.gov.
2Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: sackm@nhlbi.nih.gov.
Abstract
Caloric overconsumption in vertebrates promotes adipose and liver fat accumulation while perturbing the gut microbiome. This triad triggers pattern recognition receptor (PRR)-mediated immune cell signaling and sterile inflammation. Moreover, immune system activation perpetuates metabolic consequences, including the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic hepatic steatohepatitis (NASH). Recent findings show that sensing of nutrient overabundance disrupts the activity and homeostasis of the central cellular energy-generating organelle, the mitochondrion. In parallel, whether caloric excess-initiated PRR signaling and mitochondrial perturbations are coordinated to amplify this inflammatory process in NASH progression remains in question. We hypothesize that altered mitochondrial function, classic PRR signaling, and complement activation in response to nutrient overload together play an integrated role across the immune cell landscape, leading to liver inflammation and NASH progression.