Cellular mechanisms of BBR in reverting dysfunction in NAFLD. Nutrient stress induced a series of alterations in the liver, including mitochondrial dysfunction, ER stress, proinflammatory cytokines and endotoxin elevation, and decreased VLDL secretion. BBR is partitioned toward several pathways in protecting fatty liver. (1) BBR phosphorylates α subunit of AMPK through regulating AMP/ATP ratio, and activation of AMPK can inhibit SREBPs to suppress de novo lipogenesis, increasing PPARα expression to enhance fatty acid oxidation in the liver. (2) BBR improves insulin sensitivity by normalize insulin signaling pathway, and BBR reduces pro-inflammatory cytokines production, counteracting ER stress, thus leading to the reviving of insulin signaling transduction. (3) BBR blocks intestinal endotoxin into liver, endotoxin is a major risk factor for NAFLD progression, BBR may mediate gut environment and reduce epithelial gut permeability, which are subsequently avoid the endotoxemia into circulation; (4) BBR promote VLDL secretion by increase ApoB assembly. Additionally, the extrahepatic role of BBR that mediates fatty acid, hormones, and cytokines entering liver also contributes to the lipid-lowering effects of BBR.