A systems biology approach to the hepatic role of the oxysterol receptor LXR in the regulation of lipogenesis highlights a cross-talk with PPARα

Ducheix, Simon; Podechard, Normand; Lasserre, Frédèric; Polizzi, Arnaud; Pommier, Aurélien; Murzilli, Stefania; Lisio, Chiara Di; D’Amore, Simona; Bertrand‐Michel, Justine; Montagner, Alexandra; Pineau, Thierry; Loiseau, Nicolas; Lobaccaro, Jean Marc; Martin, Pascal G.P.; Guillou, Hervé

doi:10.1016/j.biochi.2012.09.028

Cited by 23 publications

(18 citation statements)

References 46 publications

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“…Mature SREBP-1c proteins target and directly bind to downstream genes encoding enzymes involved in lipogenesis, such as ACC1, FASN, SCD1, and GPAT [37]. Based on the activation of SREBP-1c through TSH, we examined the increase in the mRNA levels of these genes and quantified the hepatic triglyceride contents, consistent with the idea that PPARa activation promotes lipogenesis [14,21,22]. The results suggested that SREBP-1c is required for the increase in the hepatic triglyceride content through TSH.…”

Section: Discussionmentioning

confidence: 84%

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Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity

Fang

Wang

Lü

et al. 2014

Journal of Hepatology

122

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Section: Discussionmentioning

confidence: 84%

“…Accumulating evidences suggest that PPARa activation promotes lipogenesis and SREBP-1c expression [14,21,22]. Subsequently, we determined whether PPARa was involved in the regulation of SREBP-1c by TSH.…”

Section: Gene Expression Profiles and Indispensable Role Of Srebp-1c mentioning

confidence: 98%

Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity

Fang

Wang

Lü

et al. 2014

Journal of Hepatology

122

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“…Since the nuclear receptor LXR is key for the insulin-stimulated transcriptional regulation of SREBP-1c (29), we examined its activity in liver of Grb14i mice. The significant overlap of genes dysregulated by Grb14 silencing with genes controlled by LXR (determined by microarrays from LXR␣-LXR␤ double knockout mice [LXR DKO] [25]) suggested that Grb14 silencing in liver induced an LXR DKO-like phenotype (Fig. 3A).…”

Section: Resultsmentioning

confidence: 99%

“…Gene set enrichment analyses (GSEA) (24) were performed with a data set from mice with LXR knockout in liver (GEO no. GSE38083 [25]) and with a data set from mice with a genetic activation of Nrf2 in liver (GEO no. GSE15633 [26]).…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance

Popineau

Morzyglod

Carré

et al. 2016

Molecular and Cellular Biology

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A long-standing paradox in the pathophysiology of metabolic diseases is the selective insulin resistance of the liver. It is characterized by a blunted action of insulin to reduce glucose production, contributing to hyperglycemia, while de novo lipogenesis remains insulin sensitive, participating in turn to hepatic steatosis onset. The underlying molecular bases of this conundrum are not yet fully understood. Here, we established a model of selective insulin resistance in mice by silencing an inhibitor of insulin receptor catalytic activity, the growth factor receptor binding protein 14 (Grb14) in liver. Indeed, Grb14 knockdown enhanced hepatic insulin signaling but also dramatically inhibited de novo fatty acid synthesis. In the liver of obese and insulin-resistant mice, downregulation of Grb14 markedly decreased blood glucose and improved liver steatosis. Mechanistic analyses showed that upon Grb14 knockdown, the release of p62/sqstm1, a partner of Grb14, activated the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), which in turn repressed the lipogenic nuclear liver X receptor (LXR). Our study reveals that Grb14 acts as a new signaling node that regulates lipogenesis and modulates insulin sensitivity in the liver by acting at a crossroad between the insulin receptor and the p62-Nrf2-LXR signaling pathways.

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“…The human LXRα is a subtype of LXR that is expressed in the liver and its under-or over-activation eventually leads to steatosis (143). …”

Section: Effect Of Aroclor 1260 On the Human Liver-x-receptor Alphamentioning

confidence: 99%

Evaluating the effects of aroclor 1260 in non-alcoholic fatty liver disease : the role of xenobiotic receptors.

Wahlang¹

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A systems biology approach to the hepatic role of the oxysterol receptor LXR in the regulation of lipogenesis highlights a cross-talk with PPARα

Cited by 23 publications

References 46 publications

Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity

Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity

Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance

Evaluating the effects of aroclor 1260 in non-alcoholic fatty liver disease : the role of xenobiotic receptors.

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