scholarly journals Docosahexaenoic Acid Suppresses Expression of Adipogenic Tetranectin through Sterol Regulatory Element-Binding Protein and Forkhead Box O Protein in Pigs

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2315
Author(s):  
Jui-Ting Yang ◽  
Yu-Jen Chen ◽  
Chao-Wei Huang ◽  
Ya-Chin Wang ◽  
Harry J. Mersmann ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Binding Sites ◽  
Binding Protein ◽  
Regulatory Element ◽  
Forkhead Box ◽  
Transcriptional Suppression ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Tetranectin (TN), a plasminogen-binding protein originally involved in fibrinolysis and bone formation, was later identified as a secreted adipokine from human and rat adipocytes and positively correlated with adipogenesis and lipid metabolism in adipocytes. To elucidate the nutritional regulation of adipogenic TN from diets containing different sources of fatty acids (saturated, n-6, n-3) in adipocytes, we cloned the coding region of porcine TN from a cDNA library and analyzed tissue expressions in weaned piglets fed with 2% soybean oil (SB, enriched in n-6 fatty acids), docosahexaenoic acid oil (DHA, an n-3 fatty acid) or beef tallow (BT, enriched in saturated and n-9 fatty acids) for 30 d. Compared with tissues in the BT- or SB-fed group, expression of TN was reduced in the adipose, liver and lung tissues from the DHA-fed group, accompanied with lowered plasma levels of triglycerides and cholesterols. This in vivo reduction was also confirmed in porcine primary differentiated adipocytes supplemented with DHA in vitro. Then, promoter analysis was performed. A 1956-bp putative porcine TN promoter was cloned and transcription binding sites for sterol regulatory-element binding protein (SREBP)-1c or forkhead box O proteins (FoxO) were predicted on the TN promoter. Mutating binding sites on porcine TN promoters showed that transcriptional suppression of TN by DHA on promoter activity was dependent on specific response elements for SREBP-1c or FoxO. The inhibited luciferase promoter activity by DHA on the TN promoter coincides with reduced gene expression of TN, SREBP-1c, and FoxO1 in human embryonic kidney HEK293T cells supplemented with DHA. To conclude, our current study demonstrated that the adipogenic TN was negatively regulated by nutritional modulation of DHA both in pigs in vivo and in humans/pigs in vitro. The transcriptional suppression by DHA on TN expression was partly through SREBP-1c or FoxO. Therefore, down-regulation of adipogenic tetranectin associated with fibrinolysis and adipogenesis may contribute to the beneficial effects of DHA on ameliorating obesity-induced metabolic syndromes such as atherosclerosis and adipose dysfunctions.

scholarly journals A New Role for Sterol Regulatory Element Binding Protein 1 Transcription Factors in the Regulation of Muscle Mass and Muscle Cell Differentiation

2009 ◽  
Vol 30 (5) ◽  
pp. 1182-1198 ◽  
Author(s):  
Virginie Lecomte ◽  
Emmanuelle Meugnier ◽  
Vanessa Euthine ◽  
Christine Durand ◽  
Damien Freyssenet ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Muscle Mass ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Myogenic Program

ABSTRACT The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.

Transcriptional regulation of human SREBP-1c (sterol-regulatory-element-binding protein-1c): a key regulator of lipogenesis

2004 ◽  
Vol 32 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Tarling ◽  
A. Salter ◽  
A. Bennett
Keyword(s):  
Transcription Factor ◽  
Sequence Analysis ◽  
Binding Sites ◽  
Binding Protein ◽  
Regulatory Element ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Sterol-regulatory-element-binding protein 1c (SREBP-1c) is one member of the family of transcription factors that stimulate sterol and fatty-acid biosynthesis in animal cells. Human SREBP-1c, mapped to chromosome 17p11.2, is expressed in liver, intestine, skeletal muscle and adipocytes. A section of genomic sequence from a chromosome 17 library, thought to contain the SREBP-1c promoter, was cloned. Putative transcription-factor-binding sites and a potential transcriptional start site were identified using the Genomatix Suite of sequence analysis tools (MatInspector®). Sequence analysis showed the human promoter to be 42% identical with the previously published mouse sequence. Two novel transcription-factor-binding sites were identified: those for PDX-1 (pancreatic–duodenal homoeobox-1) and HNF-4 (hepatic nuclear factor-4). Co-transfection experiments with overexpression plasmids for PDX-1 and HNF-4 suggested that both factors stimulate SREBP-1c gene expression, although further work is required to ascertain their mechanisms of action.

scholarly journals MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo

2010 ◽  
Vol 107 (40) ◽  
pp. 17321-17326 ◽  
Author(s):  
T. Horie ◽  
K. Ono ◽  
M. Horiguchi ◽  
H. Nishi ◽  
T. Nakamura ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Effects of fatty acids on gene expression: role of peroxisome proliferator-activated receptor α, liver X receptor α and sterol regulatory element-binding protein-1c

2002 ◽  
Vol 61 (3) ◽  
pp. 371-374 ◽  
Author(s):  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Dietary Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver X Receptor Α ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

scholarly journals Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements

2004 ◽  
Vol 385 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Lauren M. CAGEN ◽  
Xiong DENG ◽  
Henry G. WILCOX ◽  
Edwards A. PARK ◽  
Rajendra RAGHOW ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Rat Hepatocytes ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Cis Acting ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The enhanced synthesis of fatty acids in the liver and adipose tissue in response to insulin is critically dependent on the transcription factor SREBP-1c (sterol-regulatory-element-binding protein 1c). Insulin increases the expression of the SREBP-1c gene in intact liver and in hepatocytes cultured in vitro. To learn the mechanism of this stimulation, we analysed the activation of the rat SREBP-1c promoter and its truncated or mutated congeners driving a luciferase reporter gene in transiently transfected rat hepatocytes. The rat SREBP-1c promoter contains binding sites for LXR (liver X receptor), Sp1, NF-Y (nuclear factor-Y) and SREBP itself. We have found that each of these sites is required for the full stimulatory response of the SREBP-1c promoter to insulin. Mutation of either the putative LXREs (LXR response elements) or the SRE (sterol response element) in the proximal SREBP-1c promoter reduced the stimulatory effect of insulin by about 50%. Insulin and the LXR agonist TO901317 increased the association of SREBP-1 with the SREBP-1c promoter. Ectopic expression of LXRα or SREBP-1c increased activity of the SREBP-1c promoter, and this effect is further enhanced by insulin. The Sp1 and NF-Y sites adjacent to the SRE are also required for full activation of the SREBP-1c promoter by insulin. We propose that the combined actions of the SRE, LXREs, Sp1 and NF-Y elements constitute an insulin-responsive cis-acting unit of the SREBP-1c gene in the liver.

scholarly journals In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression

2007 ◽  
Vol 363 (2) ◽  
pp. 329-335 ◽  
Author(s):  
Yoshinori Takeuchi ◽  
Naoya Yahagi ◽  
Yoshimi Nakagawa ◽  
Takashi Matsuzaka ◽  
Ritsuko Shimizu ◽  
...  
Keyword(s):  
Promoter Analysis ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Maprotiline Suppresses Cholesterol Biosynthesis and Hepatocellular Carcinoma Progression Through Direct Targeting of CRABP1

2021 ◽  
Vol 12 ◽  
Author(s):  
Cancan Zheng ◽  
Yidong Zhu ◽  
Qinwen Liu ◽  
Tingting Luo ◽  
Wenwen Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Antitumor Effects ◽  
Element Binding Protein ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death and has a poor prognosis worldwide, thus, more effective drugs are urgently needed. In this article, a small molecule drug library composed of 1,056 approved medicines from the FDA was used to screen for anticancer drugs. The tetracyclic compound maprotiline, a highly selective noradrenergic reuptake blocker, has strong antidepressant efficacy. However, the anticancer effect of maprotiline remains unclear. Here, we investigated the anticancer potential of maprotiline in the HCC cell lines Huh7 and HepG2. We found that maprotiline not only significantly restrained cell proliferation, colony formation and metastasis in vitro but also exerted antitumor effects in vivo. In addition to the antitumor effect alone, maprotiline could also enhance the sensitivity of HCC cells to sorafenib. The depth studies revealed that maprotiline substantially decreased the phosphorylation of sterol regulatory element-binding protein 2 (SREBP2) through the ERK signaling pathway, which resulted in decreased cholesterol biosynthesis and eventually impeded HCC cell growth. Furthermore, we identified cellular retinoic acid binding protein 1 (CRABP1) as a direct target of maprotiline. In conclusion, our study provided the first evidence showing that maprotiline could attenuate cholesterol biosynthesis to inhibit the proliferation and metastasis of HCC cells through the ERK-SREBP2 signaling pathway by directly binding to CRABP1, which supports the strategy of repurposing maprotiline in the treatment of HCC.

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