Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.

PTEN loss activates PI3K–AKT signaling, and mTORC1 stimulates pyrimidine synthesis through S6K1-mediated CAD phosphorylation. This exploratory public-data analysis tested whether PTEN deletion in primary prostate cancer is associated with CAD, mTORC1 and pyrimidine-synthesis expression, and whether these survive protein-level and confounder analyses. In 485 primary tumors from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD; 159 PTEN-deleted), deletion was associated with higher CAD mRNA (Hedges’ g = 0.57) and higher Hallmark mTORC1 scores (g = 0.54). In 342 tumors with reverse-phase protein-array data, deletion was accompanied by lower PTEN protein and higher AKT Ser473 phosphorylation but not by a higher pre-specified mTORC1 phospho-output composite (g = −0.02), itself uncorrelated with the transcriptional score. In a pre-specified model adding purity, TP53, RB1, ERG fusion and batch (n = 276), the PTEN–CAD association was absent (β = −0.002; p = 0.96), whereas the mTORC1-score association persisted. In a post hoc decomposition, ERG fusion, which co-occurs with PTEN deletion (odds ratio 3.6), changed the coefficient most. Across eight cohorts, a small PTEN mRNA–CAD association (g = 0.23) was attenuated to 0.14 after ERG adjustment, with overlapping confidence intervals (Hartung–Knapp p = 0.071). Bulk-tumor pathway signatures and PTEN–CAD associations need protein-level and ERG-aware interpretation.