Direct effects of iodothyronines on excess fat storage in rat hepatocytes

Grasselli, Elena; Voci, Adriana; Canesi, Laura; Matteis, Rita De; Goglia, Fernando; Cioffi, Federica; Fugassa, E; Gallo, Gabriella; Vergani, Laura

doi:10.1016/j.jhep.2010.09.027

Cited by 63 publications

(63 citation statements)

References 46 publications

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“…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%

“…We first verified the time course of lipid accumulation in rat hepatoma FaO cells exposed to a FFA mixture (oleate/ palmitate 2:1 molar ratio), according to the model of 'cellular steatosis' described in human hepatoma HepG2 cells (Feldstein et al 2004) and in primary rat hepatocytes (Feldstein et al 2004, Grasselli et al 2011. FFA exposure induced a rapid time-dependent increase in lipid accumulation, evaluated by densitometric analysis of ORO staining, reaching a plateau at 3-6 h (about threefold with respect to controls; P%0 .…”

Section: Effects Of Exogenous Ffa-induced Lipid Accumulation In Fao Cmentioning

confidence: 99%

“…Lipid-loaded FaO cells were then treated for 24 h with two different concentrations of T 2 or T 3 (10 K6 and 10 K5 M), as described previously for primary rat hepatocytes (Grasselli et al 2011). As a preliminary experiment, the dose-response curves were assessed for both iodothyronines in the range of 10 K7 -10 K5 M, and no significant effect on the TAG content was observed at the lowest dose (10 K7 M) of both T 2 and T 3 (data not shown).…”

Section: Effects Of Iodothyronines On Lipid Accumulationmentioning

confidence: 99%

“…As a preliminary experiment, the dose-response curves were assessed for both iodothyronines in the range of 10 K7 -10 K5 M, and no significant effect on the TAG content was observed at the lowest dose (10 K7 M) of both T 2 and T 3 (data not shown). The incubation time and doses of iodothyronines were in the range of those typically employed for in vitro experiments on gene expression (Ball et al 1997, Grasselli et al 2011 or lipid metabolism (Giudetti et al 2005). Moreover, several studies reported that a concentration of 10 K6 M T 3 was required to trigger non-genomic effects ) such as to increase IP3 and Ca 2C levels in BDL cholangiocytes (Fava et al 2007).…”

Section: Effects Of Iodothyronines On Lipid Accumulationmentioning

confidence: 99%

“…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). However, whether these effects were mediated by receptor-dependent or independent mechanisms has not been clarified yet.…”

Section: Introductionmentioning

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: Rna Extraction and Real-time Rt-pcrmentioning

confidence: 99%

Section: Effects Of Exogenous Ffa-induced Lipid Accumulation In Fao Cmentioning

confidence: 99%

Section: Effects Of Iodothyronines On Lipid Accumulationmentioning

confidence: 99%

Section: Effects Of Iodothyronines On Lipid Accumulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 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

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3,5,3′triiodo‐L‐thyronine induces SREBP‐1 expression by non‐genomic actions in human HEP G2 cells

Gnoni

Rochira

Leone

et al. 2012

Journal Cellular Physiology

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Liver is an important target for thyroid hormone actions. T(3) exerts its effects by two mechanisms: (i) Genomic actions consisting of T(3) link to nuclear receptors that bind responsive elements in the promoter of target genes, (ii) non-genomic actions including integrin αvb3 receptor-mediated MAPK/ERK and PI3K/Akt/mTOR-C1 activation. SREBP-1a, SREBP-1c, and SREBP-2 are transcription factors involved in the regulation of lipogenic genes. We show in Hep G2 cells that T(3) determined a dose- and time-dependent increase in the level of the precursor form of SREBP-1 without affecting SREBP-1 mRNA abundance. T(3) also induced phosphorylation of ERK1/2, Akt and of mTOR-C1 target S6K-P70, and the cytosol-to-membrane translocation of PKC-α. Modulation of SREBP-1 protein level by T(3) was dependent on MAPK/ERK, PI3K/Akt/mTOR-C1 pathway activation since the MEK inhibitor PD98059 or the PI3K inhibitor LY294002 abolished the stimulatory effect of T(3) . Conversely, the effect of T(3) on SREBP-1 level was enhanced by using rapamycin, mTOR-C1 inhibitor. These data suggest a negative control of mTOR-C1 target S6K-P70 on PI3K/Akt pathway. The effect of T(3) on SREBP-1 content increased also by using PKC inhibitors. These inhibitors increased the action of T(3) on Akt phosphorylation suggesting that conventional PKCs may work as negative regulators of the T(3) -dependent SREBP-1 increase. T(3) effects were partially abrogated by tetrac, an inhibitor of the T(3) -αvβ3 receptor interaction and partially evoked by T(3) analog T(3) -agarose. These findings support a model in which T(3) activates intracellular signaling pathways which may be involved in the increment of SREBP-1 level through an IRES-mediated translation mechanism.

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Frataxin‐Mediated PINK1–Parkin‐Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin

Liu

Lin

et al. 2018

Molecular Nutrition Food Res

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Direct effects of iodothyronines on excess fat storage in rat hepatocytes

Cited by 63 publications

References 46 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

3,5,3′triiodo‐L‐thyronine induces SREBP‐1 expression by non‐genomic actions in human HEP G2 cells

Frataxin‐Mediated PINK1–Parkin‐Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin

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