Chenodeoxycholic acid, an endogenous FXR ligand alters adipokines and reverses insulin resistance

Shihabudeen, Mohamed Sham; Roy, Debasish; James, Joanna L.; Thirumurugan, Kavitha

doi:10.1016/j.mce.2015.07.012

Cited by 51 publications

(29 citation statements)

References 54 publications

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“…Stressed adipocytes secrete pro-inflammatory cytokines and chemokines, and express markers that are sensed by local immune cells resulting in a shift from an anti-inflammatory profile to an M1 macrophage pro-inflammatory polarization (Wensveen et al, 2015). In differentiated adipocytes the exposure to palmitate leads to an increased oxidant production, NF-κB activation, and expression of chemoattractants (MCP-1, serum amyloid A3) (Yeop Han et al, 2010) and different cytokines (Shihabudeen et al, 2015). Supporting a direct action of EC on adipocytes, both EC and its metabolites mitigated palmitate-induced release of cytokines (Il-6, TNFα) and chemokines (MCP-1).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

Bettaieb

Cremonini

Kang

et al. 2016

The International Journal of Biochemistry & Cell Biology

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Obesity and type 2 diabetes (T2D) are major public health concerns. Visceral adipose tissue inflammation is considered a significant contributor to obesity-associated T2D development. We previously showed that the flavan-3-ol (−)-epicatechin (EC) can mitigate insulin resistance in mice fed a high fat diet (HFD). This study investigated the capacity of EC to inhibit visceral adipose tissue inflammation occurring as a consequence of HFD consumption in C57BL/6J mice, and characterized the underlying mechanisms. In association with the development of obesity and insulin resistance, HFD consumption caused inflammation in the visceral adipose tissue as evidenced by activation of the pro-inflammatory transcription factor NF-κB and increased tissue levels of the macrophage marker F4/80, tumor necrosis factor alpha (TNFα), and the chemokine MCP-1. EC supplementation mitigated all these events. In addition, we observed activation of the three branches of the unfolded protein response (UPR), and upregulation of NADPH oxidases NOX4 and NOX2 in visceral fat of mice fed HFD. These can account, at least in part, for the associated oxidative stress and activation of the redox sensitive NF-κB. Notably, EC supplementation mitigated this and the release of pro-inflammatory proteins from metabolically stressed adipocytes. Attenuation of adipocyte endoplasmic reticulum (ER) and oxidative stress by EC could contribute to decreased inflammation and improved visceral adipose tissue insulin sensitivity. Our results support the concept that consumption of EC-rich foods could mitigate obesity-associated insulin resistance through attenuation of adipose tissue inflammation.

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

Bettaieb

Cremonini

Kang

et al. 2016

The International Journal of Biochemistry & Cell Biology

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“…The endogenous FXR ligand chenodeoxycholic acid suppresses chemerin in palmitate‐treated 3T3‐L1 cells , demonstrating that different cells display reverse effects upon the activation of nuclear receptors. In line with this, the PPARgamma agonist rosiglitazone lowers chemerin in supernatants of HepG2 cells and elevates it in LX‐2 cells.…”

Section: Discussionmentioning

confidence: 99%

Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis

Pohl

Haberl

Rein-Fischboeck

et al. 2016

Eur J Clin Investigation

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“…TCA is implicated in the induction of proinflammatory cytokines and activates ERK1/2 by hepatocytes, indicating a role in inflammation (82, 83). Both CDCA, the endogenous ligand for FXR (84), and UDCA have neuroprotective properties and are used as N‐methyl‐ d ‐aspartate receptor and γ‐aminobutyric receptor antagonists to treat AD (85, 86). A reduction in CDCA accompanied by decreased FXR signaling in WD‐fed mice suggests the significance of BAs in regulating cognitive function.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet–induced systemic inflammation, microglial activation, and reduced neuroplasticity

et al. 2018

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The goal of this study was to identify the intrinsic links that explain the effect of a Western diet (WD) on cognitive dysfunction. Specific pathogen-free, wild-type mice were fed either a control diet (CD) or a high-fat, high-sucrose WD after weaning and were euthanized at 10 mo of age to study the pathways that affect cognitive health. The results showed that long-term WD intake reduced hippocampal synaptic plasticity and the level of brain-derived neurotrophic factor mRNA in the brain and isolated microglia. A WD also activated ERK1/2 and reduced postsynaptic density-95 in the brain, suggesting postsynaptic damage. Moreover, WD-fed mice had increased inflammatory signaling in the brain, ileum, liver, adipose tissue, and spleen, which was accompanied by microglia activation. In the brain, as well as in the digestive tract, a WD reduced signaling regulated by retinoic acid and bile acids (BAs), whose receptors form heterodimers to control metabolism and inflammation. Furthermore, a WD intake caused dysbiosis and dysregulated BA synthesis with reduced endogenous ligands for BA receptors, i.e., farnesoid X receptor and G-protein-coupled bile acid receptor in the liver and brain. Together, dysregulated BA synthesis and dysbiosis were accompanied by systemic inflammation, microglial activation, and reduced neuroplasticity induced by WD.-Jena, P. K., Sheng, L., Di Lucente, J., Jin, L.-W., Maezawa, I., Wan, Y.-J. Y. Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity.

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Chenodeoxycholic acid, an endogenous FXR ligand alters adipokines and reverses insulin resistance

Cited by 51 publications

References 54 publications

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis

Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet–induced systemic inflammation, microglial activation, and reduced neuroplasticity

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