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- Duparc, T., et al.
(author)
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Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism
- 2017
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 66:4, s. 620-632
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Journal article (peer-reviewed)abstract
- Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing nonalcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-alpha, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.
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| 2. |
- Gopinathan, L., et al.
(author)
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Emi2 Is Essential for Mouse Spermatogenesis
- 2017
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:3, s. 697-708
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Journal article (peer-reviewed)abstract
- The meiotic functions of Emi2, an inhibitor of the APC/C complex, have been best characterized in oocytes where it mediates metaphase II arrest as a component of the cytostatic factor. We generated knockout mice to determine the in vivo functions of Emi2-in particular, its functions in the testis, where Emi2 is expressed at high levels. Male and female Emi2 knockout mice are viable but sterile, indicating that Emi2 is essential for meiosis but dispensable for embryonic development and mitotic cell divisions. We found that, besides regulating cell-cycle arrest in mouse eggs, Emi2 is essential for meiosis I progression in spermatocytes. In the absence of Emi2, spermatocytes arrest in early diplotene of prophase I. This arrest is associated with decreased Cdk1 activity and was partially rescued by a knockin mouse model of elevated Cdk1 activity. Additionally, we detected expression of Emi2 in spermatids and sperm, suggesting potential post-meiotic functions for Emi2.
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| 4. |
- Zamioudis, Christos, et al.
(author)
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Rhizobacterial volatiles and photosynthesis-related signals coordinate MYB72 expression in Arabidopsis roots during onset of induced systemic resistance and iron-deficiency responses
- 2015
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In: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 84:2, s. 309-322
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Journal article (peer-reviewed)abstract
- In Arabidopsis roots, the transcription factor MYB72 plays a dual role in the onset of rhizobacteria-induced systemic resistance (ISR) and plant survival under conditions of limited iron availability. Previously, it was shown that MYB72 coordinates the expression of a gene module that promotes synthesis and excretion of iron-mobilizing phenolic compounds in the rhizosphere, a process that is involved in both iron acquisition and ISR signaling. Here, we show that volatile organic compounds (VOCs) from ISR-inducing Pseudomonas bacteria are important elicitors of MYB72. In response to VOC treatment, MYB72 is co-expressed with the iron uptake-related genes FERRIC REDUCTION OXIDASE2 (FRO2) and IRON-REGULATED TRANSPORTER1 (IRT1) in a manner that is dependent on FER-LIKE IRON DEFICIENCY TRANSCRIPTION FACTOR (FIT), indicating that MYB72 is an intrinsic part of the plant's iron-acquisition response that is typically activated upon iron starvation. However, VOC-induced MYB72 expression is activated independently of iron availability in the root vicinity. Moreover, rhizobacterial VOC-mediated induction of MYB72 requires photosynthesis-related signals, while iron deficiency in the rhizosphere activates MYB72 in the absence of shoot-derived signals. Together, these results show that the ISR- and iron acquisition-related transcription factor MYB72 in Arabidopsis roots is activated by rhizobacterial volatiles and photosynthesis-related signals, and enhances the iron-acquisition capacity of roots independently of the iron availability in the rhizosphere. This work highlights the role of MYB72 in plant processes by which root microbiota simultaneously stimulate systemic immunity and activate the iron-uptake machinery in their host plants. Significance Statement Plant roots intimately interact with plant growth-promoting rhizobacteria that prime the plant immune system and aid in iron uptake two functions facilitated by the root-specific transcription factor MYB72. Here we show how MYB72 and iron uptake responses are systemically activated by photosynthesis-related signals and volatiles produced by plant growth-promoting rhizobacteria, highlighting the important role of beneficial root microbiota in supporting plant growth and health.
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