Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity, insulin resistance, and type II-diabetes and now also known as a leading cause of cirrhosis and hepatocellular carcinoma. Functionally, the NASH liver is compromised by chronic inflammation, microvascular dysfunction, and fibrosis aggravating the initial metabolic derangements. Using single-cell RNA-sequencing, we have here analyzed whole liver plasticity in a murine model of diet-induced, advanced NASH. We analyzed the fibrogenic transition of hepatic stellate cells (HSCs) from pericytes to collagen-producing cells. Stellate cell-specific Gs-protein-coupled receptors and the bile-acid receptor NR1H4/FXR seemingly dominated HSC biology in the healthy liver, forming the basis for multimodal diurnal signaling, but deteriorated in activated HSCs in advanced NASH. Expression of key signaling components were validated in situ in human and murine liver tissue supporting the translatability of our findings and pharmacological relevance in restoration of healthy liver function. We further interrogated the NASH-associated rerouting of mononuclear phagocytes. In addition to two emerging populations of Trem2-expressing monocyte-derived macrophages, we found a population of CD207-positive macrophages significantly expanded in advanced NASH and likely derived from both incoming monocytes and Kupffer cells. We conclude that HSCs of the healthy liver are pivotal for hepatic sensing and integration of postprandial cues, which sustain HSC quiescence and - as inferred from paracrine mediator - overall sinusoidal health. HSC activation driven by parenchymal damage, responding macrophages, and other effectors in the NASH microenvironment is hence not only causally implicated in fibrogenesis but also sinusoidal sensory loss impeding restoration of hepatic homeostasis.