The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform
Frédéric Bost - One of the best experts on this subject based on the ideXlab platform.
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Metformin-induced energy deficiency leads to the inhibition of Lipogenesis in prostate cancer cells
Oncotarget, 2015Co-Authors: Camille Loubiere, Thomas Goiran, Zied Djabari, Jean-françois Tanti, Kathiane Laurent, Frédéric BostAbstract:The deregulation of lipid metabolism is a hallmark of tumor cells, and elevated Lipogenesis has been reported in prostate cancer. Metformin, a drug commonly prescribed for type II diabetes, displays antitumor properties. Here, we show that metformin inhibits Lipogenesis in several prostate cancer cell lines. In LNCaP cells, this effect parallels the decrease of key lipogenic proteins: ACC (acetyl-CoA carboxylase), FASN (fatty acid synthase) and SREBP1c (sterol regulatory element binding protein-1c), whereas there is no modification in DU145 and PC3 cells. Despite the relatively high level of lipogenic proteins induced by the overexpression of a constitutively active form of SREBP1c or treatment with androgens, metformin is still able to inhibit Lipogenesis. Metformin does not alter the concentration of malonyl-CoA (the fatty acid precursor), and it only slightly decreases the NADPH levels, which is a co-factor required for Lipogenesis, in LNCaP. Finally, we show that the inhibitory effect of metformin on Lipogenesis is primarily due to a cellular energy deficit. Metformin decreases ATP in a dose-dependent manner, and this diminution is significantly correlated with the inhibition of Lipogenesis in LNCaP and DU145. Indeed, the effect of metformin is linked to changes in the ATP content rather than the regulation of protein expression. Our results describe a new mechanism of action for metformin on prostate cancer metabolism.
Camille Loubiere - One of the best experts on this subject based on the ideXlab platform.
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Metformin-induced energy deficiency leads to the inhibition of Lipogenesis in prostate cancer cells
Oncotarget, 2015Co-Authors: Camille Loubiere, Thomas Goiran, Zied Djabari, Jean-françois Tanti, Kathiane Laurent, Frédéric BostAbstract:The deregulation of lipid metabolism is a hallmark of tumor cells, and elevated Lipogenesis has been reported in prostate cancer. Metformin, a drug commonly prescribed for type II diabetes, displays antitumor properties. Here, we show that metformin inhibits Lipogenesis in several prostate cancer cell lines. In LNCaP cells, this effect parallels the decrease of key lipogenic proteins: ACC (acetyl-CoA carboxylase), FASN (fatty acid synthase) and SREBP1c (sterol regulatory element binding protein-1c), whereas there is no modification in DU145 and PC3 cells. Despite the relatively high level of lipogenic proteins induced by the overexpression of a constitutively active form of SREBP1c or treatment with androgens, metformin is still able to inhibit Lipogenesis. Metformin does not alter the concentration of malonyl-CoA (the fatty acid precursor), and it only slightly decreases the NADPH levels, which is a co-factor required for Lipogenesis, in LNCaP. Finally, we show that the inhibitory effect of metformin on Lipogenesis is primarily due to a cellular energy deficit. Metformin decreases ATP in a dose-dependent manner, and this diminution is significantly correlated with the inhibition of Lipogenesis in LNCaP and DU145. Indeed, the effect of metformin is linked to changes in the ATP content rather than the regulation of protein expression. Our results describe a new mechanism of action for metformin on prostate cancer metabolism.
James M Ntambi - One of the best experts on this subject based on the ideXlab platform.
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genetic control of de novo Lipogenesis role in diet induced obesity
Critical Reviews in Biochemistry and Molecular Biology, 2010Co-Authors: Maggie S Strable, James M NtambiAbstract:De novo Lipogenesis (DNL) is a complex yet highly regulated metabolic pathway, and transcription factors such as liver X receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), and carbohydrate response element binding protein (ChREBP) exert significant control over the de novo synthesis of fatty acids. An increase in de novo Lipogenesis (DNL) is an important contributor to increased fat mass, while a reduction in Lipogenesis may be protective against the development of obesity. In this review, we explore fatty acid synthesis in the context of new insights gleaned from global and tissue-specific gene knockout mouse models of enzymes involved in fatty acid synthesis, namely acetyl-CoA carboxylase, fatty acid synthase, fatty acid elongase 6, and stearoyl-CoA desaturase 1. A disruption in fatty acid synthesis, induced by the deficiency of any one of these enzymes, affects lipid metabolism and in some cases may protect against obesity in a tissue and gene-specific manner, as discussed in deta...
Weizhen Zhang - One of the best experts on this subject based on the ideXlab platform.
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ghrelin promotes hepatic Lipogenesis by activation of mtor pparγ signaling pathway
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Ziru Li, Geyang Xu, Chao Zhang, Hong Tang, Xinxin Xiang, Yin Li, Jing Zhao, Michael W Mulholland, Weizhen ZhangAbstract:Abstract Although ghrelin has been demonstrated to stimulate energy intake and storage through a central mechanism, its effect on hepatic lipid metabolism remains largely uncharacterized. Ghrelin receptor antagonism or gene deletion significantly decreased obesity-associated hepatic steatosis by suppression of de novo Lipogenesis, whereas exogenous ghrelin stimulated Lipogenesis, leading to hepatic lipid accumulation in mice. The effects of ghrelin were mediated by direct activation of its receptor on hepatocytes. Cultured hepatocytes responded to ghrelin with increased lipid content and expression of Lipogenesis-related genes. Ghrelin increased phosphorylation of S6, the downstream target of mammalian target of rapamycin (mTOR) signaling in cultured hepatocytes, whereas ghrelin receptor antagonism reduced hepatic phosphorylation of S6 in db/db mice. Inhibition of mTOR signaling by rapamycin markedly attenuated ghrelin-induced up-regulation of Lipogenesis in hepatocytes, whereas activation of hepatic mTOR signaling by deletion of TSC1 increased hepatic Lipogenesis. By interacting with peroxisome proliferator-activated receptor-γ (PPARγ), mTOR mediates the ghrelin-induced up-regulation of Lipogenesis in hepatocytes. The stimulatory effect of ghrelin on hepatic Lipogenesis was significantly attenuated by PPARγ antagonism in cultured hepatocytes and in PPARγ gene-deficient mice. Our study indicates that ghrelin activates its receptor on hepatocytes to promote Lipogenesis via a mechanism involving the mTOR-PPARγ signaling pathway.
Fabienne Foufelle - One of the best experts on this subject based on the ideXlab platform.
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hepatic steatosis a role for de novo Lipogenesis and the transcription factor srebp 1c
Diabetes Obesity and Metabolism, 2010Co-Authors: P Ferre, Fabienne FoufelleAbstract:Steatosis is an accumulation of triglycerides in the liver. Although an excessive availability of plasma fatty acids is an important determinant of steatosis, lipid synthesis from glucose (Lipogenesis) is now also considered as an important contributing factor. Lipogenesis is an insulin- and glucose-dependent process that is under the control of specific transcription factors, sterol regulatory element binding protein 1c (SREBP-1c), activated by insulin and carbohydrate response element binding protein (ChREBP) activated by glucose. Insulin induces the maturation of SREBP-1c by a proteolytic mechanism initiated in the endoplasmic reticulum (ER). SREBP-1c in turn activates glycolytic gene expression, allowing glucose metabolism, and lipogenic genes in conjunction with ChREBP. Lipogenesis activation in the liver of obese markedly insulin-resistant steatotic rodents is then paradoxical. Recent data suggest that the activation of SREBP-1c and thus of Lipogenesis is secondary in the steatotic liver to an ER stress. The ER stress activates the cleavage of SREBP-1c independent of insulin, thus explaining the paradoxical stimulation of Lipogenesis in an insulin-resistant liver. Inhibition of the ER stress in obese rodents decreases SREBP-1c activation and Lipogenesis and improves markedly hepatic steatosis and insulin sensitivity. ER is thus a new partner in steatosis and metabolic syndrome which is worth considering as a potential therapeutic target.