liver metabolism
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2022 ◽  
Vol 226 (1) ◽  
pp. S753
Author(s):  
Lidia Di Cerbo ◽  
Ahmed R. Hamed ◽  
Daniela Menichini ◽  
Corey Clifford ◽  
Baha M. Sibai ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingyang Xin ◽  
Qian Guo ◽  
Qingchun Lu ◽  
Juan Lu ◽  
Po-shun Wang ◽  
...  

Abstract Background The majority of mammalian genome is composed of non-coding regions, where numerous long non-coding RNAs (lncRNAs) are transcribed. Although lncRNAs have been identified to regulate fundamental biological processes, most of their functions remain unknown, especially in metabolic homeostasis. Analysis of our recent genome-wide screen reveals that Gm15441, a thioredoxin-interacting protein (Txnip) antisense lncRNA, is the most robustly induced lncRNA in the fasting mouse liver. Antisense lncRNAs are known to regulate their sense gene expression. Given that Txnip is a critical metabolic regulator of the liver, we aimed to investigate the role of Gm15441 in the regulation of Txnip and liver metabolism. Methods We examined the response of Gm15441 and Txnip under in vivo metabolic signals such as fasting and refeeding, and in vitro signals such as insulin and key metabolic transcription factors. We investigated the regulation of Txnip expression by Gm15441 and the underlying mechanism in mouse hepatocytes. Using adenovirus-mediated liver-specific overexpression, we determined whether Gm15441 regulates Txnip in the mouse liver and modulates key aspects of liver metabolism. Results We found that the expression levels of Gm15441 and Txnip showed a similar response pattern to metabolic signals in vivo and in vitro, but that their functions were predicted to be opposite. Furthermore, we found that Gm15441 robustly reduced Txnip protein expression in vitro through sequence-specific regulation and translational inhibition. Lastly, we confirmed the Txnip inhibition by Gm15441 in vivo (mice) and found that Gm15441 liver-specific overexpression lowered plasma triglyceride and blood glucose levels and elevated plasma ketone body levels. Conclusions Our data demonstrate that Gm15441 is a potent Txnip inhibitor and a critical metabolic regulator in the liver. This study reveals the therapeutic potential of Gm15441 in treating metabolic diseases.


Author(s):  
Camila Bataglini ◽  
Isabela Ramos Mariano ◽  
Sílvia Carla Ferreira Azevedo ◽  
Valder Nogueira Freire ◽  
Maria Raquel Marçal Natali ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6632
Author(s):  
Martina Tremmel ◽  
Christian Paetz ◽  
Jörg Heilmann

Several medical plants belonging to the genera Passiflora, Viola, and Crataegus accumulate flavonoid C-glycosides, which likely contribute to their efficacy. Information regarding their phase I and II metabolism in the liver are lacking. Thus, in vitro liver metabolism of orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin, all of which accumulated in Passiflora incarnata L., was investigated by incubation in subcellular systems with human liver microsomes and human liver S9 fraction. All metabolite profiles were comprehensively characterized using HPLC-DAD and UHPLC–MS/MS analysis. Mono-glycosylic flavones of the luteolin-type orientin and isoorientin showed a broad range of mono-glucuronidated and mono-sulfated metabolites, whereas for mono-glycosylic flavones of the apigenin-type vitexin and isovitexin, only mono-glucuronidates could be detected. For di-glycosylic flavones of the apigenin-type schaftosid and isoschaftosid, no phase I or II metabolites were identified. The main metabolite of isoorientin was isolated using solid-phase extraction and prep. HPLC-DAD and identified as isoorientin-3′-O-α-glucuronide by NMR analysis. A second isolated glucuronide was assigned as isoorientin 4′-O-α-glucuronide. These findings indicate that vitexin and isovitexin are metabolized preferentially by uridine 5′-diphospho glucuronosyltransferases (UGTs) in the liver. As only orientin and isoorientin showed mono-sulfated and mono-glucuronidated metabolites, the dihydroxy group in 3′,4′-position may be essential for additional sulfation by sulfotransferases (SULTs) in the liver. The diglycosylic flavones schaftoside and isoschaftoside are likely not accepted as substrates of the used liver enzymes under the chosen conditions.


Metabolites ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 751
Author(s):  
John G. Jones

The liver is a key node of whole-body nutrient and fuel metabolism and is also the principal site for detoxification of xenobiotic compounds. As such, hepatic metabolite concentrations and/or turnover rates inform on the status of both hepatic and systemic metabolic diseases as well as the disposition of medications. As a tool to better understand liver metabolism in these settings, in vivo magnetic resonance spectroscopy (MRS) offers a non-invasive means of monitoring hepatic metabolic activity in real time both by direct observation of concentrations and dynamics of specific metabolites as well as by observation of their enrichment by stable isotope tracers. This review summarizes the applications and advances in human liver metabolic studies by in vivo MRS over the past 35 years and discusses future directions and opportunities that will be opened by the development of ultra-high field MR systems and by hyperpolarized stable isotope tracers.


2021 ◽  
Vol 35 (10) ◽  
Author(s):  
Paul Kern ◽  
Nora R. Balzer ◽  
Nelli Blank ◽  
Cornelia Cygon ◽  
Klaus Wunderling ◽  
...  

2021 ◽  
Vol 35 (10) ◽  
Author(s):  
Begoña Zapatería ◽  
Julio Sevillano ◽  
María Gracia Sánchez‐Alonso ◽  
María Limones ◽  
Javier Pizarro‐Delgado ◽  
...  

2021 ◽  
Author(s):  
Damiano Patrono ◽  
Dorotea Roggio ◽  
Anna Teresa Mazzeo ◽  
Giorgia Catalano ◽  
Elena Mazza ◽  
...  

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