NF-κB; the Critical Link between Immune and Metabolic Pathways: Could NF-κB be Used as a Novel Diagnostic and Prognostic Biomarker for Non-Alcoholic Steatohepatitis?

Abstract

Background: A great number of inflammatory mediators and metabolic biomarkers have been shown to contribute to the development and progression of obesity-induced pathologies, including insulin resistance and non-alcoholic fatty liver disease (NAFLD). Many of those mediators are either targets or activators of Nuclear Factor-κappa B (NF-κB), which is a key transcription factor that plays a pivotal role in the homeostasis and regulation of inflammatory signaling pathways in the liver. Methods: Our study population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from the visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and the liver. We evaluated the differential protein expression of NF-κB, ERβ (Estrogen Receptor β), NFATc1 (Nuclear factor of activated T-cells) and PGC1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) by immunohistochemistry. Results: We found that NF-κB is the key biomarker in a complicated intra-and inter-tissue co-expression network that interconnects metabolic and immune signaling pathways. We also demonstrated a possible role in lipid metabolism and the development of skeletal muscle insulin resistance and non-alcoholic steatohepatitis (NASH). Conclusions: Our findings suggest that NF-κB may be the critical link between immune and metabolic pathways and could represent a future preventive and therapeutic target against obesity-induced metabolic diseases. We hope that our study will contribute to the better understanding of the complex inter-tissue connections that are disrupted in obesity and its associated comorbidities.