Grasselli Elena, Voci Adriana, Canesi Laura, Salis Annalisa, Damonte Gianluca, Compalati Andrea D, Goglia Fernando, Gallo Gabriella, Vergani Laura
Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università degli Studi di Genova, Genova, Italy.
Cell Physiol Biochem. 2014;33(2):344-56. doi: 10.1159/000356674. Epub 2014 Feb 5.
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.
FaO cells were exposed to oleate/palmitate, then treated with T2.
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).
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.
背景/目的：脂肪酸是细胞的主要能量储存形式和主要膜成分。在肝细胞中，脂肪酸被酯化为三酰甘油（TAGs）并储存在脂滴（LDs）中。从脂滴的脂肪酸和蛋白质含量、脂质氧化及分泌方面，研究了3,5-二碘-L-甲状腺原氨酸（T2）对肝脂肪变性体外模型的降脂作用。
将FaO细胞暴露于油酸/棕榈酸，然后用T2处理。
T2减少了脂滴的数量和大小，并通过降低饱和脂肪酸（SFA）与单不饱和脂肪酸（MUFA）的含量改变了其酰基组成，从而逆转了SFA/MUFA比值。在“脂肪变性”细胞中，与脂滴相关的蛋白质脂肪分化相关蛋白（ADRP）、富含氧化组织的PAT蛋白（OXPAT）和脂肪甘油三酯脂肪酶（ATGL）的表达增加，并被T2进一步上调。此外，T2通过上调肉碱-棕榈酰转移酶（CPT1）、解偶联蛋白2（UCP2）和极长链酰基辅酶A脱氢酶（VLCAD）刺激线粒体氧化。
T2导致脂滴中TAGs的动员，并刺激脂肪酸尤其是SFA的线粒体氧化代谢，从而使脂滴中富含MUFA。这种作用可能保护肝细胞免受比MUFA毒性更大的SFA过量的影响。
