Non-alcoholic fatty liver disease (NAFLD) (now also known as MASLD or Metabolic dysfunction-associated steatotic liver disease) is the most common chronic liver disease globally, with a rising prevalence. NAFLD is linked to imbalances in various metabolites, including those produced by gut microbiota, like short-chain fatty acids, that influence NAFLD pathogenesis. A high-fat diet (HFD) is a significant factor contributing to the development and progression of NAFLD, a condition characterized by excessive fat accumulation in the liver. Mice subjected to a high-fat diet exhibit phase shifts in the circadian expression of clock genes. However, the extent to which these disruptions affect both the host metabolome and microbiome-derived metabolites remains insufficiently explored. Given the dynamic interplay between host metabolism and the gut microbiota, understanding how circadian misalignment influences metabolic reprogramming is crucial. This report showed that a distinct reprogramming of the phasic metabolome and metabolic gene expression accompanied NAFLD. Our results show phase-specific metabolic shifts characterized by an "active-high" and "rest-low" expression pattern of key metabolic genes. We established further that microbiota-derived metabolites may mediate circadian disruption and NAFLD progression. Vis-à-vis, we will also discuss quantitative aspects of the analysis to understand the relative contributions of metabolome and meta-metabolome on physiology via two different perturbations.