Yee Jennifer K, Wahjudi Paulin N, Vega Juan, Lim Shu, Martin Ashley, Patterson Mary E, Cohen Joshua N, Mao Catherine S, Lee Wai-Nang P
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Walter Martin Research Building, Torrance, CA 90502, USA.
Metabolomics. 2013 Aug 1;9(4):809-816. doi: 10.1007/s11306-013-0511-3.
Stearoyl-CoA desaturase enzyme 1 (SCD1) is a lipogenic enzyme that is upregulated in obesity, insulin resistance, and cancer. Since glucose is a substrate for both de novo fatty acid synthesis and deoxyribose synthesis, we hypothesized that SCD1 affects these multiple synthetic pathways through changes in glucose utilization. This study determined glucose utilization for fatty acid synthesis and cell proliferation in 3T3-L1 preadipocytes during SCD1 inhibition. The effects of SCD1 on cellular metabolism as mediated by its monounstaurated fatty acid products (palmitoleate and oleate) were also observed. 3T3-L1 preadipocytes underwent differentiation induction in conjunction with one of the following treatments for 4 days: (A) no treatment, (B) SCD1 inhibitor CGX0290, (C) CGX0290 + palmitoleate, or (D) CGX0290 + oleate. All cells received medium with 50 % [UC]-glucose. Cells were harvested on day 7 for studies of fatty acid metabolism, tricarboxylic acid (TCA) cycle activities, and deoxyribose synthesis. CGX0290 decreased fatty acid desaturation, glucose utilization for fatty acid synthesis (acetyl-CoA enrichment), and de novo synthesis. CGX0290 treatment also led to decreased cell density through increased cell death. Further analysis showed that deoxyribose new synthesis and oxidative pentose phosphate pathway activity were unchanged, while non-oxidative transketolase pathway activity was stimulated. Palmitoleate and oleate supplementation each partially ameliorated the effects of CGX0290. In 3T3-L1 cells, SCD1 promotes glucose utilization for fatty acid synthesis. In cell proliferation, SCD1 may promote cell survival, but does not impact the oxidative pathway of deoxyribose production. These effects may be mediated through the production of palmitoleate and oleate.
硬脂酰辅酶A去饱和酶1（SCD1）是一种在肥胖、胰岛素抵抗和癌症中上调的脂肪生成酶。由于葡萄糖是从头脂肪酸合成和脱氧核糖合成的底物，我们推测SCD1通过改变葡萄糖利用来影响这些多种合成途径。本研究确定了在SCD1抑制期间3T3-L1前脂肪细胞中用于脂肪酸合成和细胞增殖的葡萄糖利用情况。还观察了SCD1由其单不饱和脂肪酸产物（棕榈油酸酯和油酸酯）介导的对细胞代谢的影响。3T3-L1前脂肪细胞在进行分化诱导的同时，与以下处理之一联合进行4天：（A）不处理，（B）SCD1抑制剂CGX0290，（C）CGX0290 + 棕榈油酸酯，或（D）CGX0290 + 油酸酯。所有细胞均接受含50%[UC]-葡萄糖的培养基。在第7天收获细胞，用于脂肪酸代谢、三羧酸（TCA）循环活性和脱氧核糖合成的研究。CGX0290降低了脂肪酸去饱和、用于脂肪酸合成的葡萄糖利用（乙酰辅酶A富集）和从头合成。CGX0290处理还通过增加细胞死亡导致细胞密度降低。进一步分析表明，脱氧核糖的新合成和氧化戊糖磷酸途径活性未改变，而非氧化转酮醇酶途径活性受到刺激。棕榈油酸酯和油酸酯的补充各自部分改善了CGX0290的作用。在3T3-L1细胞中，SCD1促进用于脂肪酸合成的葡萄糖利用。在细胞增殖方面，SCD1可能促进细胞存活，但不影响脱氧核糖产生的氧化途径。这些作用可能通过棕榈油酸酯和油酸酯的产生来介导。
