| 1. |
- Martínez-Sánchez, Noelia, et al.
(author)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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In: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Journal article (peer-reviewed)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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| 2. |
- Tedesco, Sara, et al.
(author)
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Proteomic and lipidomic analysis of primary mouse hepatocytes exposed tometal and metal oxide nanoparticles
- 2015
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In: Journal of Integrated Omics. - : Proteomass Scientific Society. - 2182-0287. ; 5:1
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Journal article (peer-reviewed)abstract
- The global analysis of the cellular lipid and protein content upon exposure to metal and metal oxide nanoparticles (NPs) can provide an overview of the possible impact of exposure. Proteomic analysis has been applied to understand the nanoimpact however the relevance of the alteration on the lipidic profile has been underestimated. In our study, primary mouse hepatocytes were treated with ultra-small (US) TiO2-USNPs as well as ZnO-NPs, CuO-NPs and Ag-NPs. The protein extracts were analysed by 2D-DIGE and quantified by imaging software and the selected differentially expressed proteins were identified by nLC-ESI-MS/MS. In parallel, lipidomic analysis of the samples was performed using thin layer chromatography (TLC) and analyzed by imaging software. Our findings show an overall ranking of the nanoimpact at the cellular and molecular level: TiO2-USNPs2-USNPs did not have oxidative capacity and were not cytotoxic. The most common cellular impact of the exposure was the down-regulation of proteins. The proteins identified were involved in urea cycle, lipid metabolism, electron transport chain, metabolism signaling, cellular structure and we could also identify nuclear proteins. CuO-NPs exposure decreased phosphatidylethanolamine and phosphatidylinositol and caused down-regulation of electron transferring protein subunit beta. Ag-NPs exposure caused increased of total lipids and triacylglycerol and decrease of sphingomyelin. TiO2-USNPs also caused decrease of sphingomyelin as well as up-regulation of ATP synthase and electron transferring protein alfa. ZnO-NPs affected the proteome in a concentration-independent manner with down-regulation of RNA helicase. ZnO-NPs exposure did not affect the cellular lipids. To our knowledge this work represents the first integrated proteomic and lipidomic approach to study the effect of NPs exposure to primary mouse hepatocytes in vitro.
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