Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid
Abstract Background Elevation of exogenous free fatty acid (FFA) level leads to insulin resistance (IR) in liver, IR is manifested by elevated hepatic glucose production. We aim to study whether inhibition of endogenous fatty acid synthesis could decrease hepatic glucose production. Methods Low-pass...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12944-019-1026-3 |
| _version_ | 1828834772850311168 |
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| author | Xiu-Ping Bai Feng Dong Guo-Hua Yang Lei Zhang |
| author_facet | Xiu-Ping Bai Feng Dong Guo-Hua Yang Lei Zhang |
| author_sort | Xiu-Ping Bai |
| collection | DOAJ |
| description | Abstract Background Elevation of exogenous free fatty acid (FFA) level leads to insulin resistance (IR) in liver, IR is manifested by elevated hepatic glucose production. We aim to study whether inhibition of endogenous fatty acid synthesis could decrease hepatic glucose production. Methods Low-passage HepG2 cells derived from human liver tissue were cultured in medium supplemented with FFA to induce IR, the influences of sterol regulatory element binding protein-1c (SREBP-1c) silencing on glucose production of HepG2 cells were investigated, and genes responsible for fatty acid and glucose metabolism were detected by real-time PCR. Results Compared with HepG2 cells cultured in normal growth medium, glucose production of HepG2 cells treated by FFA was significantly increased {[(0.28 ± 0.01) vs (0.83 ± 0.02)] umol.ug− 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of phosphoenolpyruvate carboxylase kinase (PEPCK) and glucose-6-phosphatase (G6PC) in HepG2 cells increased by more than 5-fold and 3-fold, respectively; the mRNA expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) increased by approximately 4-fold and 1.1-fold, respectively; the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) changed slightly. Compared with the scrambled siRNA control, glucose production of HepG2 cells treated by FFA significantly increased after SREBP-1c silencing {[(0.018 ± 0.001) vs (0.028 ± 0.002)] umol.ug− 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of PEPCK and G6PC increased by approximately 1.5-fold and 5-fold, respectively, but the mRNA expression of FAS, SCD1 and CPT-1 changed slightly. Conclusions SREBP-1c silencing further augmented glucose production of HepG2 cells treated by FFA significantly, genes responsible for fatty acid synthesis and gluconeogenesis played an important role in this process. SREBP-1c functions not only as a lipid regulator but also plays an important role in regulation of glucose metabolism. |
| first_indexed | 2024-12-12T17:46:02Z |
| format | Article |
| id | doaj.art-df56dc0c584047979f25b941223c2543 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-12T17:46:02Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-df56dc0c584047979f25b941223c25432022-12-22T00:16:55ZengBMCLipids in Health and Disease1476-511X2019-04-0118111210.1186/s12944-019-1026-3Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acidXiu-Ping Bai0Feng Dong1Guo-Hua Yang2Lei Zhang3Endocrinology Division, The Second Hospital of ShanXi Medical UniversityDiabetes Division, University of Texas Health Science CenterCentral Laboratory, The Second Hospital of ShanXi Medical UniversityEndocrinology Division, The Second Hospital of ShanXi Medical UniversityAbstract Background Elevation of exogenous free fatty acid (FFA) level leads to insulin resistance (IR) in liver, IR is manifested by elevated hepatic glucose production. We aim to study whether inhibition of endogenous fatty acid synthesis could decrease hepatic glucose production. Methods Low-passage HepG2 cells derived from human liver tissue were cultured in medium supplemented with FFA to induce IR, the influences of sterol regulatory element binding protein-1c (SREBP-1c) silencing on glucose production of HepG2 cells were investigated, and genes responsible for fatty acid and glucose metabolism were detected by real-time PCR. Results Compared with HepG2 cells cultured in normal growth medium, glucose production of HepG2 cells treated by FFA was significantly increased {[(0.28 ± 0.01) vs (0.83 ± 0.02)] umol.ug− 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of phosphoenolpyruvate carboxylase kinase (PEPCK) and glucose-6-phosphatase (G6PC) in HepG2 cells increased by more than 5-fold and 3-fold, respectively; the mRNA expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1) increased by approximately 4-fold and 1.1-fold, respectively; the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) changed slightly. Compared with the scrambled siRNA control, glucose production of HepG2 cells treated by FFA significantly increased after SREBP-1c silencing {[(0.018 ± 0.001) vs (0.028 ± 0.002)] umol.ug− 1 protein, n = 6 wells, P < 0.01}; the mRNA expression of PEPCK and G6PC increased by approximately 1.5-fold and 5-fold, respectively, but the mRNA expression of FAS, SCD1 and CPT-1 changed slightly. Conclusions SREBP-1c silencing further augmented glucose production of HepG2 cells treated by FFA significantly, genes responsible for fatty acid synthesis and gluconeogenesis played an important role in this process. SREBP-1c functions not only as a lipid regulator but also plays an important role in regulation of glucose metabolism.http://link.springer.com/article/10.1186/s12944-019-1026-3Glucose productionSREBP-1c silencingFree fatty acidHepG2 cells |
| spellingShingle | Xiu-Ping Bai Feng Dong Guo-Hua Yang Lei Zhang Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid Lipids in Health and Disease Glucose production SREBP-1c silencing Free fatty acid HepG2 cells |
| title | Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid |
| title_full | Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid |
| title_fullStr | Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid |
| title_full_unstemmed | Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid |
| title_short | Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid |
| title_sort | influences of sterol regulatory element binding protein 1c silencing on glucose production in hepg2 cells treated with free fatty acid |
| topic | Glucose production SREBP-1c silencing Free fatty acid HepG2 cells |
| url | http://link.springer.com/article/10.1186/s12944-019-1026-3 |
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