Effects of 3,5-Diiodo-L-Thyronine Administration on the Liver of High Fat Diet-Fed Rats

Grasselli, Elena; Canesi, Laura; Voci, Adriana; Matteis, Rita De; Demori, Ilaria; Fugassa, E; Vergani, Laura

doi:10.3181/0710-rm-266

Cited by 36 publications

(45 citation statements)

References 45 publications

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“…Also T 2 , as T 3 , is able to stimulate both resting metabolic rate and mitochondrial activity in hypothyroid rats (Moreno et al 1997). Moreover, when administered to rats receiving a high-fat diet, T 2 was able to both prevent (Lanni et al 2005, Grasselli et al 2008 and reduce (Mollica et al 2009) the development of liver steatosis. Once entering the cell, THs mostly bind to specific nuclear receptors (TRs) acting as ligand-dependent transcription factors ('receptor-mediated' effects).…”

Section: Introductionmentioning

confidence: 94%

“…The anti-steatosic effects of iodothyronines observed in vivo (Lanni et al 2005, Grasselli et al 2008 could not distinguish between their direct effects on the liver and the secondary effects due to upstream changes in endocrine or metabolic pathways. Subsequent in vitro experiments using primary rat hepatocytes overloaded with lipids demonstrated that T 2 and T 3 were able to directly reduce the excess fat (Grasselli et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…3 mM of each primer, 10 ng cDNA, 1! SYBR Green PCR Master Mix and was analyzed in 96-well optical reaction by Chromo4 System PCR apparatus using the thermal protocol described elsewhere (Grasselli et al 2008(Grasselli et al , 2011. The primer pairs employed in this study are listed in Table 1.…”

Section: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

“…Animal maintenance and treatment were carried out as described elsewhere (Grasselli et al 2008) according to the guidelines of the European Community Council for animal care and use.…”

Section: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

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Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

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Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-L-diiodothyronine (T 2 ), as well as 3,3 0 ,5-L-triiodothyronine (T 3 ), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T 2 and T 3 to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRa1 and TRb1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T 2 or T 3 for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-a, -g, -d) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O 2 consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARg mRNA expression, and a decrease in PPARd and SCD1 mRNA expression. The addition of T 2 or T 3 to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARa, PPARg, and AOX expression; iii) increase in PPARd expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T 2 and T 3 are not mediated by TRs.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

“…Animal maintenance and treatment were carried out as described elsewhere (Grasselli et al 2008) according to the guidelines of the European Community Council for animal care and use.…”

Section: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

See 2 more Smart Citations

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Grasselli

Voci

Canesi

et al. 2011

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…First strand cDNA was synthesized from 1 μg of total RNA (24). Quantitative RT-PCR was performed in quadruplicate in a final volume of 25 μl containing 0.3 μM of each primer, 10 ng cDNA, 1x SybrGreen PCR Master Mix and were analyzed in 96-well optical reaction by 7900 HT fast real-time PCR system (Applied Biosystems, Monza, Italy).…”

Section: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

PAT protein mRNA expression in primary rat hepatocytes: effects of exposure to fatty acids

Grasselli

Voci²,

Pesce³

et al. 2010

Int J Mol Med

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Abstract. Excess energy is stored as neutral lipids in lipid droplets (LDs) whose surface is coated by PAT proteins, each playing a distinct cellular function. The adipocyte differentiation-related protein (ADRP) and tail-interacting protein (TIP47) are expressed almost ubiquitously, whereas the oxidative tissue-enriched PAT protein (OXPAT) is expressed in specific tissues, such as the liver. In rat liver, only ADRP expression has been documented. This study was aimed at identifying OXPAT and TIP47 transcripts in rat hepatocytes, and investigating how their expression is modulated by excess lipids, using fat-enriched hepatocytes to mimic different degrees of steatosis. Primary rat hepatocytes were exposed to fatty acids (FFAs) for 12, 24 and 36 h. Lipid accumulation was estimated by spectrophotometric quantification of triacylglycerol. Expression of PAT proteins as well as of PPARÁ was evaluated by real-time RT-PCR. Hepatocytes exposed to FFAs showed progressive lipid accumulation. The increase in lipid content was associated with the induction of PAT protein expression. At 12 h, OXPAT and TIP47 mRNA expression was up-regulated. At longer times, the level of OXPAT transcripts remained high, whereas that of TIP47 slowly declined. Conversely, ADRP expression showed a time-dependent increase with exposure to FFAs. This study demonstrates, for the first time, the presence of OXPAT and TIP47 transcripts in rat hepatocytes, as well as their upregulation with lipid accumulation. The distinct time courses observed for the three PAT proteins during FFA exposure might reflect the different roles played by each protein in lipid metabolism in the hepatocyte. Up-regulation of TIP47 and OXPAT might represent an early response to excess lipids, while, in correspondence with a lipid overload, upregulation of ADRP could address lipids towards storage.

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3,5‐diiodo‐L‐thyronine increases de novo lipogenesis in liver from hypothyroid rats by SREBP‐1 and ChREBP‐mediated transcriptional mechanisms

et al. 2019

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Hepatic de novo lipogenesis (DNL), the process by which carbohydrates are converted into lipids, is strictly controlled by nutritional and hormonal status. 3,5‐Diiodo‐L‐thyronine (T2), a product of the 3,5,3′‐triiodo‐L‐thyronine (T3) peripheral metabolism, has been shown to mimic some T3 effects on lipid metabolism by a short‐term mechanism independent of protein synthesis. Here, we report that T2, administered for 1 week to hypothyroid rats, increases total fatty acid synthesis from acetate in isolated hepatocytes. Studies carried out on liver subcellular fractions demonstrated that T2 not only increases the activity and the expression of acetyl‐CoA carboxylase and fatty acid synthase but also of other proteins linked to DNL such as the mitochondrial citrate carrier and the cytosolic ATP citrate lyase. Parallelly, T2 stimulates the activities of enzymes supplying cytosolic NADPH needed for the reductive steps of DNL. With respect to both euthyroid and hypothyroid rats, T2 administration decreases the hepatic mRNA level of SREBP‐1, a transcription factor which represents a master regulator of DNL. However, when compared to hypothyroid rats T2 significantly increases, without bringing to the euthyroid value, the content of both mature (nSREBP‐1), and precursor (pSREBP‐1) forms of the SREBP‐1 protein as well as their ratio. Moreover, T2 administration strongly augmented the nuclear content of ChREBP, another crucial transcription factor involved in the regulation of lipogenic genes. Based on these results, we can conclude that in the liver of hypothyroid rats the transcriptional activation by T2 of DNL genes could depend, at least in part, on SREBP‐1‐ and ChREBP‐dependent mechanisms. © 2019 IUBMB Life, 2019

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Effects of 3,5-Diiodo-L-Thyronine Administration on the Liver of High Fat Diet-Fed Rats

Cited by 36 publications

References 45 publications

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells

PAT protein mRNA expression in primary rat hepatocytes: effects of exposure to fatty acids

3,5‐diiodo‐L‐thyronine increases de novo lipogenesis in liver from hypothyroid rats by SREBP‐1 and ChREBP‐mediated transcriptional mechanisms

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