Lipid sensing and lipid sensors

Scotti, Eleonora; Gilardi, Federica; Godio, Cristina; Gers, Elise; Krneta, Jelena; Mitro, Nico; Fabiani, Emma De; Caruso, Donatella; Crestani, Maurizio

doi:10.1007/s00018-007-7280-y

Cited by 29 publications

(7 citation statements)

References 125 publications

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“…In recent years it has become clear that bile acids are important regulatory molecules capable of activating specific nuclear receptors, G-protein coupled receptors (TGR5), and various cell signaling pathways in the liver and gastrointestinal tract (2–6). Bile acids have been reported to activate the AKT pathway (insulin signaling pathway) and the nuclear receptor FXR in hepatocytes (18–21, 38–40).…”

Section: Discussionmentioning

confidence: 99%

“…Bile acids are capable of activating specific nuclear receptors [i.e., farnesoid X receptor (FXR), pregnane X receptor (PXR), Vitamin D], a Gα s -protein-coupled surface receptor (TGR-5), and cell signaling pathways (i.e., JNK1/2, ERK1/2, AKT) (2–6). Activation of FXR in the liver results in the increased expression of a number of target genes, including the bile salt export pump ABCB11 and the phospholipid transporter ABCB4.…”

mentioning

confidence: 99%

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Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

Cao

Cronk

Zha

et al. 2010

Journal of Lipid Research

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Bile acids are important regulatory molecules that can activate specific nuclear receptors and cell signaling pathways in the liver and gastrointestinal tract. In the current study, the chronic bile fistula (CBF) rat model and primary rat hepatocytes (PRH) were used to study the regulation of gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) and the gene encoding short heterodimeric partner (SHP) by taurocholate (TCA). The intestinal infusion of TCA into the CBF rat rapidly (1 h) activated the AKT (∼9-fold) and ERK1/2 (3- to 5-fold) signaling pathways, downregulated (∼50%, 30 min) the mRNA levels of PEPCK and G-6-Pase, and induced (14-fold in 3 h) SHP mRNA. TCA rapidly (∼50%, 1–2 h) downregulated PEPCK and G-6-Pase mRNA levels in PRH. The downregulation of these genes by TCA was blocked by pretreatment of PRH with pertussis toxin (PTX). In PRH, TCA plus insulin showed a significantly stronger inhibition of glucose secretion/synthesis from lactate and pyruvate than either alone. The induction of SHP mRNA in PRH was strongly blocked by inhibition of PI3 kinase or PKCζ by specific chemical inhibitors or knockdown of PKCζ by siRNA encoded by a recombinant lentivirus. Activation of the insulin signaling pathway appears to be linked to the upregulation of farnesoid X receptor functional activity and SHP induction.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

Cao

Cronk

Zha

et al. 2010

Journal of Lipid Research

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“…They are also endogenous ligands for the farnesoid X receptor/bile acid receptor (FXR), 6 which regulates bile acid homeostasis by modulating the expression of genes in liver and small intestine that control the synthesis and enterohepatic circulation of bile acids (reviewed in Refs. 1 and 2). …”

Section: Introductionmentioning

confidence: 99%

AKR1B7 Is Induced by the Farnesoid X Receptor and Metabolizes Bile Acids

Schmidt

Schmidt²,

Holmstrom³

et al. 2011

Journal of Biological Chemistry

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Although bile acids are crucial for the absorption of lipophilic nutrients in the intestine, they are cytotoxic at high concentrations and can cause liver damage and promote colorectal carcinogenesis. The farnesoid X receptor (FXR), which is activated by bile acids and abundantly expressed in enterohepatic tissues, plays a crucial role in maintaining bile acids at safe concentrations. Here, we show that FXR induces expression of Akr1b7 (aldo-keto reductase 1b7) in murine small intestine, colon, and liver by binding directly to a response element in the Akr1b7 promoter. We further show that AKR1B7 metabolizes 3-keto bile acids to 3β-hydroxy bile acids that are less toxic to cultured cells than their 3α-hydroxy precursors. These findings reveal a feed-forward, protective pathway operative in murine enterohepatic tissues wherein FXR induces AKR1B7 to detoxify bile acids.

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“…The link between bile acids and a multitude of deleterious effects in humans has increased the interest in better understanding of the bile acid physiology [11, 12]. Although, mass spectrometry based methods are highly useful for analyzing bile acids, establishing the relationship between glycine- and taurine-conjugation has not been possible so far [13–16].…”

Section: Introductionmentioning

confidence: 99%

Bile Acids Conjugation in Human Bile Is Not Random: New Insights from ¹H‐NMR Spectroscopy at 800 MHz

Gowda

Shanaiah

Cooper

et al. 2009

Lipids

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Bile acids constitute a group of structurally closely related molecules and represent the most abundant constituents of human bile. Investigations of bile acids have garnered increased interest owing to their recently discovered additional biological functions including their role as signaling molecules that govern glucose, fat and energy metabolism. Recent NMR methodological developments have enabled single-step analysis of several highly abundant and common glycine- and taurine- conjugated bile acids, such as glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid. Investigation of these conjugated bile acids in human bile employing high field (800 MHz) 1H-NMR spectroscopy reveals that the ratios between two glycine-conjugated bile acids and their taurine counterparts correlate positively (R2 = 0.83–0.97; p = 0.001 × 10−2–0.006 × 10−7) as do the ratios between a glycine-conjugated bile acid and its taurine counterpart (R2 = 0.92–0.95; p = 0.004 × 10−3–0.002 × 10−10). Using such correlations, concentration of individual bile acids in each sample could be predicted in good agreement with the experimentally determined values. These insights into the pattern of bile acid conjugation in human bile between glycine and taurine promise useful clues to the mechanism of bile acids’ biosynthesis, conjugation and enterohepatic circulation, and may improve our understanding of the role of individual conjugated bile acids in health and disease.

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Lipid sensing and lipid sensors

Cited by 29 publications

References 125 publications

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

AKR1B7 Is Induced by the Farnesoid X Receptor and Metabolizes Bile Acids

Bile Acids Conjugation in Human Bile Is Not Random: New Insights from ¹H‐NMR Spectroscopy at 800 MHz

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Lipid sensing and lipid sensors

Cited by 29 publications

References 125 publications

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway

AKR1B7 Is Induced by the Farnesoid X Receptor and Metabolizes Bile Acids

Bile Acids Conjugation in Human Bile Is Not Random: New Insights from 1H‐NMR Spectroscopy at 800 MHz

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Bile Acids Conjugation in Human Bile Is Not Random: New Insights from ¹H‐NMR Spectroscopy at 800 MHz