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Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro.
Eur J Pharmacol. 2011 Dec 15; 672(1-3):38-44.EJ

Abstract

Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet-induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-α. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-α. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation.

Authors+Show Affiliations

School of Life Science, Handong Global University, Pohang, Kyungbuk 791-708, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21970804

Citation

Kim, Eunha, et al. "Inhibition of stearoyl-CoA Desaturase1 Activates AMPK and Exhibits Beneficial Lipid Metabolic Effects in Vitro." European Journal of Pharmacology, vol. 672, no. 1-3, 2011, pp. 38-44.
Kim E, Lee JH, Ntambi JM, et al. Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro. Eur J Pharmacol. 2011;672(1-3):38-44.
Kim, E., Lee, J. H., Ntambi, J. M., & Hyun, C. K. (2011). Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro. European Journal of Pharmacology, 672(1-3), 38-44. https://doi.org/10.1016/j.ejphar.2011.09.172
Kim E, et al. Inhibition of stearoyl-CoA Desaturase1 Activates AMPK and Exhibits Beneficial Lipid Metabolic Effects in Vitro. Eur J Pharmacol. 2011 Dec 15;672(1-3):38-44. PubMed PMID: 21970804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro. AU - Kim,Eunha, AU - Lee,Jung-Han, AU - Ntambi,James M, AU - Hyun,Chang-Kee, Y1 - 2011/09/29/ PY - 2011/06/24/received PY - 2011/09/18/revised PY - 2011/09/19/accepted PY - 2011/10/6/entrez PY - 2011/10/6/pubmed PY - 2012/3/8/medline SP - 38 EP - 44 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 672 IS - 1-3 N2 - Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet-induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-α. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-α. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/21970804/Inhibition_of_stearoyl_CoA_desaturase1_activates_AMPK_and_exhibits_beneficial_lipid_metabolic_effects_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(11)01155-1 DB - PRIME DP - Unbound Medicine ER -