The subsequent investigation of HMGCS2—the rate-limiting enzyme in ketogenesis—demonstrated congruent temporal dynamics: (1) during weeks 0–4, hepatic HMGCS2 expression was substantially upregulated in NAFLD-T2DM mice compared to the NAFLD controls, exhibiting progressive elevation over time, and (2) beyond week 6, HMGCS2 expression underwent significant suppression in the NAFLD-T2DM models compared to the NAFLD counterparts and continued to decline until the 10th week. Here, HMGCS2 is linked to type 2 diabetes mellitus.