Dietary sulfur amino acid restriction improves glucose homeostasis through hepatic <i>de novo</i> serine synthesis.

ABSTRACT: Dietary sulfur amino acid restriction (SAAR) improves whole-body glucose homeostasis, elevates liver insulin action, and lowers liver triglycerides. These adaptations are associated with an increased expression of hepatic de novo serine synthesis enzymes, phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1). This study tested the hypothesis that enhanced hepatic serine synthesis is necessary for glucose and lipid adaptations to SAAR. Hepatocyte-specific PSAT1 knockout (KO) mice and wild type (WT) littermates were fed a high-fat control or SAAR diet. In WT mice, SAAR increased liver PSAT1 protein (~70-fold), serine concentration (~2-fold), and ¹³C-serine (~20-fold) following an intravenous infusion of [U-¹³C]glucose. The elevated l

SUBMITTER: Ortega AF 

PROVIDER: S-EPMC12633052 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature