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3,5-diiodo-L-thyronine modifies the lipid droplet composition in a model of hepatosteatosis. | LitMetric

AI Article Synopsis

  • The study investigates how 3,5-diiodo-L-thyronine (T2) affects lipid droplets and fatty acid composition in liver cells (hepatocytes) that accumulate fat (hepatosteatosis).
  • T2 was found to decrease the number and size of lipid droplets while increasing the proportion of monounsaturated fatty acids (MUFA) over saturated fatty acids (SFA), thus altering their fatty acid profiles.
  • Additionally, T2 enhances mitochondrial fatty acid oxidation and increases levels of proteins that promote fat breakdown, suggesting T2 could help protect liver cells from the harmful effects of excess saturated fats.

Article Abstract

Background/aims: Fatty acids are the main energy stores and the major membrane components of the cells. In the hepatocyte, fatty acids are esterified to triacylglycerols (TAGs) and stored in lipid droplets (LDs). The lipid lowering action of 3,5-diiodo-L-thyronine (T2) on an in vitro model of hepatosteatosis was investigated in terms of fatty acid and protein content of LDs, lipid oxidation and secretion.

Methods: FaO cells were exposed to oleate/palmitate, then treated with T2.

Results: T2 reduced number and size of LDs, and modified their acyl composition by decreasing the content of saturated (SFA) vs monounsaturated (MUFA) fatty acids thus reversing the SFA/MUFA ratio. The expression of the LD-associated proteins adipose differentiation-related protein (ADRP), oxidative tissue-enriched PAT protein (OXPAT), and adipose triglyceride lipase (ATGL) was increased in 'steatotic' cells and further up-regulated by T2. Moreover, T2 stimulated the mitochondrial oxidation by up-regulating carnitine-palmitoyl-transferase (CPT1), uncoupling protein 2 (UCP2) and very long-chain acyl-coenzyme A dehydrogenase (VLCAD).

Conclusions: T2 leads to mobilization of TAGs from LDs and stimulates mitochondrial oxidative metabolism of fatty acids, in particular of SFAs, and thus enriches of MUFAs the LDs. This action may protect the hepatocyte from excess of SFAs that are more toxic than MUFAs.

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Source
http://dx.doi.org/10.1159/000356674DOI Listing

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