Docosahexaenoic Acid Induces Adipose Differentiation-Related Protein through Activation of Retinoid X Receptor in Human Choriocarcinoma BeWo Cells

Suzuki, Kazushige; Takahashi, K.; Nishimaki-Mogami, Tomoko; Kagechika, Hiroyuki; Yamamoto, Masahide; Itabe, Hiroyuki

doi:10.1248/bpb.32.1177

Cited by 28 publications

(25 citation statements)

References 32 publications

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“…It is well known that the addition of fatty acid to various cells induces ADRP expression and LD formation and that PPAR-RXR heterodimers are involved in mRNA expression of the ADRP gene (19)(20)(21)(22)(23)(24)(25). We tested the effect of fatty acids on the distribution of ADRP using HuH-7 hepatocytes, but we did not observe ADRP distribution in the iLD fractions by…”

Section: Induction Of Adrp-associated Ild Fractions In Huh-7 Human Hementioning

confidence: 93%

“…The expression of Adrp mRNA is induced not only in adipocytes but also in many other types of cells upon lipid accumulation (17)(18)(19)(20)(21). It is reported that peroxisome-proliferator activated protein (PPAR)-retinoid X receptor (RXR) heterodimers are responsible for ADRP transcription, while PPAR ␥ is the major subtype in adipose tissue and the placenta ( 22,23 ), PPAR ␦ is crucial in macrophages ( 19 ), and PPAR ␣ acts in the liver ( 20,24 ).…”

Section: Immunoblot Analysismentioning

confidence: 99%

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Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver

Takahashi

Sasabe

Ohshima

et al. 2010

Journal of Lipid Research

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Supplementary key words fatty liver • hepatocytes • HuH-7 • lipid droplets • NASH • phospholipase C • protein kinase A • sucrose density gradient centrifugationIntracellular lipid droplets (LD) are cellular organelles observed ubiquitously in physiological and pathological conditions. LDs are composed of a core of neutral lipids containing cholesteryl esters and/or triacylglycerol (TG), a surrounding surface monolayer of phospholipids, and several associated proteins. LDs are considered to be a storage site of neutral lipids and to play a role in wholebody energy homeostasis ( 1-3 ).A number of proteomic studies on LD in various cells have revealed the unique protein profi les of LD ( 4-8 ). A Abstract Cellular lipid droplets (LD) are organelles involved in cellular lipid metabolism. When liver cellular components were fractionated using sucrose density gradient centrifugation, adipose differentiation-related protein (ADRP) was distributed in both the top and bottom fractions, which correspond to the LD and membranous fractions, respectively, in the mouse liver under normal feeding conditions. After overnight fasting, triacylglycerol and ADRP increased nearly 2.5-fold in the mouse liver, and a portion appeared in the intermediate-density LD (iLD) fractions. ADRP in the iLD fractions was also increased in a mouse nonalcoholic steatohepatitis model induced by methione/choline-defi cient diet. When HuH-7 human hepatoma cells were incubated with oleic acid for 24 h, the amount of ADRP increased, and it was distributed in both the LD and membrane fractions. However, ADRP appeared in the iLD fractions upon treatment of HuH-7 cells with glucagon. This behavior of ADRP was cAMP-dependent, as the ADRP-positive iLD fractions were induced by dibutylyl cAMP and were blocked by protein kinase A inhibitors. A portion of ADRP colocalized microscopically with calnexin, which is present in the iLD fractions, by treatment of HuH-7 cells or human primary hepatocytes with oleic acid and glucagon, but not by treatment with oleic acid alone. Glucagon has a role in the reorganization of endoplasmic reticulum membranes to generate ADRP-associated lipid-poor particles in hepatic cells, which is related to LD formation during lipid storage. -Takahashi, K., N. Sasabe, K. Ohshima, K. Kitazato, R. Kato, Y. Masuda, M. Tsurumaki, T. Obama, S-i. Okudaira, J. Aoki, H. Arai, T. Yamaguchi, and H. Itabe. MEXT, 2005MEXT, -2009 Abbreviations: Ab, antibody; ADRP, adipose differentiation-related protein; ER, endoplasmic reticulum; GRP78/BiP, glucose-regulated protein of 78-kDa/binding protein; iLD, intermediate-density lipid droplet; LD, lipid droplet; MCD, methione/choline defi cient; MTP, microsomal triacylglycerol transfer protein; NASH; nonalcoholic steatohepatitis; OA, oleic acid; PAT, perilipin-ADRP-TIP47; PLP, 4% paraformaldehydelysine-sodium periodate; PC, phosphatidylcholine; PKA, protein kinase A; PKI, PKI14-22amide; PLC, phospholipase C; PNS, post-nuclear supernatant; PPAR, peroxisome proliferator-activated receptor; Rp, Rp-8-Br-cAMPS; SCD...

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Section: Induction Of Adrp-associated Ild Fractions In Huh-7 Human Hementioning

confidence: 93%

Section: Immunoblot Analysismentioning

confidence: 99%

Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver

Takahashi

Sasabe

Ohshima

et al. 2010

Journal of Lipid Research

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“…Cultures were treated with two different RXR pan-antagonists, HX531 and PA452 (42)(43)(44), at different concentrations: 0.1, 1, and 10 M or 1 and 10 M, respectively. These antagonists were added to the cultures at day 1, and DHA or BSA was added 1 h later; the cultures were then either treated or not treated at day 3 with PQ and the cells were fi xed 24 h later.…”

Section: Addition Of Hx531 and Pa452mentioning

confidence: 99%

“…DHA also acts as a natural RXR agonist in other cell types. In a human placental choriocarcinoma cell line, BeWo cells for instance, RXR antagonists PA451 and HX531 inhibited DHA induction of adipose differentiation-related protein ( Adrp ) mRNA and ADRP protein accumulation ( 44 ), suggesting that DHA activated RXRs to increase ADRP levels. We have previously demonstrated that DHA activates defense mechanisms to prevent apoptosis induced both by oxidative stress and the absence of trophic factors at early stages of development and turns on a program to advance differentiation of photoreceptors ( 54 ).…”

Section: Trk Receptors Were Not Involved In the Protective Effect Of Dhamentioning

confidence: 99%

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

German

Monaco

Agnolazza

et al. 2013

Journal of Lipid Research

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“…Most of the FO effects were exerted via PPARa (Sugiyama et al 2008) and other hepatic transcriptional factors such as sterol regulatory element-binding protein-1 (Yahagi et al 1999). In addition, the involvement of other nuclear receptors, such as retinoic X receptor (Suzuki et al 2009) and LXR (Howell et al 2009), has also been reported. However, the existence of other, still unknown, mechanisms has been suggested (Duplus & Forest 2002).…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

Souza¹,

Cordeiro²,

Oliveira³

et al. 2011

Journal of Endocrinology

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n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) exert important lipid-lowering effects, an effect also ascribed to thyroid hormones (TH) and TH receptor b1 (TRb1)-specific agonists. n-3 PUFA effects are mediated by nuclear receptors, such as peroxisome proliferator-activated receptors (PPAR) and others. In this study, we investigated a role for TH signaling in n-3 PUFA effects. Euthyroid and hypothyroid adult rats (methimazole-treated for 5 weeks) received FO or soybean oil (control) by oral administration for 3 weeks. In euthyroid rats, FO treatment reduced serum triglycerides and cholesterol, diminished body fat, and increased protein content of the animals. In addition, FO-treated rats exhibited higher liver expression of TRb1 and mitochondrial a-glycerophosphate dehydrogenase (mGPD), at protein and mRNA levels, but no alteration of glutathione S-transferase or type 1 deiodinase. In hypothyroid condition, FO induced reduction in serum cholesterol and increase in body protein content, but lost the ability to reduce triglycerides and body fat, and to induce TRb1 and mGDP expression. FO did not change PPARa liver abundance regardless of thyroid state; however, hypothyroidism led to a marked increase in PPARa liver content but did not alter TRb1 or TRa expression. The data suggest that part of the effect of n-3 PUFA from FO on lipid metabolism is dependent on TH signaling in specific steps and together with the marked upregulation of PPARa in liver of hypothyroid rats suggest important in vivo consequences of the cross-talking between those fatty acids and TH pathways in liver metabolism.

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Docosahexaenoic Acid Induces Adipose Differentiation-Related Protein through Activation of Retinoid X Receptor in Human Choriocarcinoma BeWo Cells

Cited by 28 publications

References 32 publications

Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver

Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

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