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Cross regulation of sirtuin 1, AMPK, and PPAR? in conjugated linoleic acid treated adipocytes.

ABSTRACT: Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor ? (PPAR?) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPAR?, thereby inhibiting its activity. This study investigated the role of SIRT1 in the response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses: 1) SIRT1 is functionally required for robust TG reduction; and 2) SIRT1, AMPK, and PPAR? cross regulate each other. These experiments were performed by using activators, inhibitors, or siRNA knockdowns that affected these pathways in t10c12 CLA-treated 3T3-L1 adipocytes. Inhibition of SIRT1 amounts or activity using siRNA, sirtinol, nicotinamide, or etomoxir attenuated the amount of TG loss, while SIRT1 activator SRT1720 increased the TG loss. SRT1720 increased AMPK activity while sirtuin-specific inhibitors decreased AMPK activity. Reciprocally, an AMPK inhibitor reduced SIRT1 activity. Treatment with t10c12 CLA increased PPAR? phosphorylation in an AMPK-dependent manner and increased the amount of PPAR? bound to SIRT1. Reciprocally, a PPAR? agonist attenuated AMPK and SIRT1 activity levels. These results indicated SIRT1 increased TG loss and that cross regulation between SIRT1, AMPK, and PPAR? occurred in 3T3-L1 adipocytes treated with t10c12 CLA.

SUBMITTER: Jiang S

PROVIDER: S-EPMC3498327 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Cross regulation of sirtuin 1, AMPK, and PPARγ in conjugated linoleic acid treated adipocytes.

Jiang Shan S Wang Wei W Miner Jess J Fromm Michael M

PloS one 20121114 11

Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor γ (PPARγ) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPARγ, thereby inhibiting its activity. This study investigat ...[more]

PMID: 23155420

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Project description:The effects of maternal conjugated linoleic acid (CLA) on embryonic development and hepatic lipid metabolism were investigated in chick embryos. A total of 180 Arbor Acres female broiler breeders (36 wk old) were randomly divided into the following 3 dietary treatment groups: a basic diet (control), a basic diet containing 0.5% CLA (CLA1), and a basic diet containing 1.0% CLA (CLA2). The females were fed for 8 wk, and the eggs from each group were collected and hatched during the last 2 wk. The results showed that the addition of dietary CLA increased the broken egg rate and reduced the fertilization rate and the egg hatchability (P < 0.05). CLA enrichment decreased the polyunsaturated and monounsaturated fatty acids and increased the saturated fatty acids in the yolk sac (P < 0.05). The yolk sac weight, body weight, and body length had a linear decrease with CLA supplementation (P < 0.05). In the developing chick embryo (at E14) and newly hatched chick (D0), the serum triglyceride concentration decreased with maternal CLA supplementation and was accompanied by a reduction in subcutaneous adipose tissue deposition. In addition, maternal CLA supplementation mediated the hepatic lipid metabolism by decreasing the mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), fatty acid synthase and acetyl-CoA carboxylase, and increasing the mRNA expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), peroxisome proliferator-activated receptors α (PPARα), liver fatty acid-binding protein, adipose triglyceride lipase and carnitine palmitoyltransferase in embryonic chick livers (P < 0.05). A drop in SREBP-1c protein expression and an increase in the protein expression of p-AMPKα and PPARα were also observed in the liver of chick embryo (P < 0.05). In conclusion, maternal CLA supplementation regulated the fatty acid composition in the yolk sac, and mediated embryonic chick development and hepatic lipometabolism, and these effects may be related to the AMPK pathway. These findings suggest the potential ability of maternal CLA supplementation to reduce fat deposition in chick embryos.

Dataset Information

Cross regulation of sirtuin 1, AMPK, and PPAR? in conjugated linoleic acid treated adipocytes.

Publications

Cross regulation of sirtuin 1, AMPK, and PPARγ in conjugated linoleic acid treated adipocytes.

Similar Datasets

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