Abstract
Recent reports demonstrated that 3,5-diiodo-l-thyronine (T(2)) was able to prevent lipid accumulation in the liver of rats fed a high-fat diet (HFD). In this study, we investigated how the rat liver responds to HFD and T(2) treatment by assessing the transcription profiles of some genes involved in the pathways of lipid metabolism: oxidation, storage and secretion. The mRNA levels of the peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ), and of their target enzymes acyl-CoA oxidase and stearoyl-CoA desaturase were evaluated by real-time RT-PCR. Moreover, the expression of the adipose triglyceride lipase involved in lipid mobilisation, of the main PAT proteins acting in lipid droplet (LD) turnover, and of apoprotein B (apo B), the major protein component of very low-density lipoproteins (VLDLs) were analysed. Overall, our data demonstrated that T(2) administration to HFD rats counteracts most of the hepatic transcriptional changes that occurred in response to the excess exogenous fat. In particular, our results suggest that T(2) may prevent the pathways leading to lipid storage in LDs, promote the processes of lipid mobilisation from LDs and secretion as VLDL, in addition to the stimulation of pathways of lipid oxidation. In conclusion, our findings might give an insight into the mechanisms underlying the anti-steatotic ability of T(2) and help to define the potential therapeutic role of T(2) for preventing or treating liver steatosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl-CoA Oxidase / genetics
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Acyl-CoA Oxidase / metabolism
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
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Apolipoproteins B / genetics
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Apolipoproteins B / metabolism
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Diiodothyronines / therapeutic use*
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Fatty Liver / immunology
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Fatty Liver / metabolism*
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Fatty Liver / pathology
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Fatty Liver / prevention & control*
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Gene Expression Regulation / drug effects*
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Lipase / genetics
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Lipase / metabolism
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Lipid Metabolism / drug effects*
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Lipoproteins, VLDL / metabolism
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Liver / drug effects*
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Liver / immunology
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Liver / metabolism
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Liver / pathology
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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Perilipin-2
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Perilipin-3
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Perilipin-5
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Peroxisome Proliferator-Activated Receptors / genetics
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Peroxisome Proliferator-Activated Receptors / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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RNA, Messenger / metabolism
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Random Allocation
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Rats
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Rats, Wistar
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Stearoyl-CoA Desaturase / genetics
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Stearoyl-CoA Desaturase / metabolism
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Vesicular Transport Proteins / genetics
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Vesicular Transport Proteins / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Apolipoproteins B
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Diiodothyronines
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Intracellular Signaling Peptides and Proteins
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Lipoproteins, VLDL
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Membrane Proteins
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Muscle Proteins
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PLIN5 protein, rat
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Perilipin-2
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Perilipin-3
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Perilipin-5
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Peroxisome Proliferator-Activated Receptors
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Plin3 protein, rat
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Protein Isoforms
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RNA, Messenger
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Vesicular Transport Proteins
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3,5-diiodothyronine
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Stearoyl-CoA Desaturase
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Acyl-CoA Oxidase
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Lipase
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PNPLA2 protein, mouse