bims-liverm Biomed News
on Liver Metabolism
Issue of 2023‒04‒09
eight papers selected by
Marti Cadena Sandoval
Columbia University
  1. The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications.
  2. ODEVIXIBAT TREATMENT INDUCES BILIARY BILE ACID SECRETION IN RESPONSIVE PATIENTS WITH BILE SALT EXPORT PUMP DEFICIENCY (PFIC2).
  3. Childhood Cholestatic Liver Diseases that Persist Into Adulthood: Lessons for the Adult Gastroenterologist.
  4. The value of bile acid spectrum in the evaluation of hepatic injury in children with infectious mononucleosis caused by Epstein Barr virus infection.
  5. Linoleic acid, an omega-6 fatty acid that reduces risk for cardiometabolic diseases: premise, promise and practical implications.
  6. The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery.
  7. Diet-induced induction of hepatic Serine/Threonine Kinase STK38 triggers proinflammation and hepatic lipid accumulation.
  8. Bile Composition - which Components Can Have Clinical Significance? A Review of the Literature.
  1. Aging Dis. 2023 Apr 01. 14(2): 261-282
    The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications.
    Shuwen Zhang, Junteng Zhou, Wenchao Wu, Ye Zhu, Xiaojing Liu.
      Bile acids (BAs), key regulators in the metabolic network, are not only involved in lipid digestion and absorption but also serve as potential therapeutic targets for metabolic disorders. Studies have shown that cardiac dysfunction is associated with abnormal BA metabolic pathways. As ligands for several nuclear receptors and membrane receptors, BAs systematically regulate the homeostasis of metabolism and participate in cardiovascular diseases (CVDs), such as myocardial infarction, diabetic cardiomyopathy, atherosclerosis, arrhythmia, and heart failure. However, the molecular mechanism by which BAs trigger CVDs remains controversial. Therefore, the regulation of BA signal transduction by modulating the synthesis and composition of BAs is an interesting and novel direction for potential therapies for CVDs. Here, we mainly summarized the metabolism of BAs and their role in cardiomyocytes and noncardiomyocytes in CVDs. Moreover, we comprehensively discussed the clinical prospects of BAs in CVDs and analyzed the clinical diagnostic and application value of BAs. The latest development prospects of BAs in the field of new drug development are also prospected. We aimed to elucidate the underlying mechanism of BAs treatment in CVDs, and the relationship between BAs and CVDs may provide new avenues for the prevention and treatment of these diseases.
    Keywords:  Bile acids; cardiomyocytes; cardiovascular diseases; metabolism; noncardiomyocytes
    DOI:  https://doi.org/10.14336/AD.2022.0817
  2. Gastroenterology. 2023 Mar 30. pii: S0016-5085(23)00567-X. [Epub ahead of print]
    ODEVIXIBAT TREATMENT INDUCES BILIARY BILE ACID SECRETION IN RESPONSIVE PATIENTS WITH BILE SALT EXPORT PUMP DEFICIENCY (PFIC2).
    M Nomden, F Kuipers, Jan B F Hulscher, Erik Lindström, Velichka Valcheva, Henkjan J Verkade.
      
    DOI:  https://doi.org/10.1053/j.gastro.2023.03.226
  3. J Clin Gastroenterol. 2023 Apr 06.
    Childhood Cholestatic Liver Diseases that Persist Into Adulthood: Lessons for the Adult Gastroenterologist.
    Alvin P Chan, Robert S Venick.
      Children with cholestatic liver diseases are increasingly living into adulthood, thanks to innovations in medical and surgical therapies. The excellent outcomes observed in pediatric liver transplantation for diseases, such as biliary atresia, have transformed the life trajectory of children born with once-fatal liver diseases. The evolution of molecular genetic testing, has helped expedite the diagnosis of other cholestatic disorders, improving the clinical management, disease prognosis, and family planning for inherited disorders, such as progressive familial intrahepatic cholestasis and bile acid synthesis disorders. The expanding list of therapeutics, including bile acids and the newer ileal bile acid transport inhibitors, has also helped slow the progression of disease and improve the quality of life for certain diseases, like Alagille syndrome. More and more children with cholestatic disorders are expected to require care from adult providers familiar with the natural history and potential complications of these childhood diseases. The aim of this review is to bridge the gap between pediatric and adult care in children with cholestatic disorders. The present review addresses the epidemiology, clinical features, diagnostic testing, treatment, prognosis, and transplant outcomes of 4 hallmark childhood cholestatic liver diseases: biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, and bile acid synthesis disorders.
    DOI:  https://doi.org/10.1097/MCG.0000000000001850
  4. Front Pediatr. 2023 ;11 1109762
    The value of bile acid spectrum in the evaluation of hepatic injury in children with infectious mononucleosis caused by Epstein Barr virus infection.
    Ren Shen, Yan Zhou, Lintao Zhang, Shanpu Yang.
      Background: Infectious mononucleosis (IM) is an acute infectious disease, caused by Epstein-Barr virus (EBV) infection, which can invade various systemic systems, among which hepatic injury is the most common. In this study, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect serum bile acid spectrum in IM children quantitatively, and to investigate its role in the early assessment of hepatic injury.Methods: This case-control study was conducted at Yuhuan People's Hospital. A total of 60 IM children and 30 healthy children were included in the study. Among 60 children with IM, 30 had hepatic injury, and 30 without hepatic injury. The clinical and laboratory data were analyzed, and the serum bile acid spectrum and lymphocyte subsets were evaluated in the three groups.
    Results: There were statistically significant differences in cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid(GDCA), glycolithocholic acid (GLCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid(TUDCA), percentage of NK cells, CD4+ and CD8+ in IM hepatic injury group, without hepatic injury group, and the healthy control group (P < 0.05). The percentage of NK cells was positively correlated with TCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA, TUDCA (P < 0.05). CD4+ was positively correlated with CA, TCA and TCDCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05). CD8+ was positively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05); it was negatively correlated with CA, TCA and TCDCA (P < 0.05). ROC curve analysis showed that CD8+, GDCA and GLCA had high predictive value for hepatic injury in IM patients.
    Conclusions: UPLC-MS/MS method can sensitively detect the changes in serum bile acid spectrum before hepatic injury in children with IM, which is helpful for early assessment of hepatic injury in children with IM. The changes in lymphocyte subsets in IM children are related to some bile acid subfractions, which may be related to IM hepatic injury.
    Keywords:  bile acid; epstein-Barr virus; hepatic injury; infectious mononucleosis; lymphocyte subsets
    DOI:  https://doi.org/10.3389/fped.2023.1109762
  5. Curr Opin Clin Nutr Metab Care. 2023 May 01. 26(3): 288-292
    Linoleic acid, an omega-6 fatty acid that reduces risk for cardiometabolic diseases: premise, promise and practical implications.
    Martha Ann Belury.
      PURPOSE OF REVIEW: As heart disease and type 2 diabetes mellitus (T2DM) cases continue to rise, identifying lifestyle modifications to prevent cardiometabolic disease (CMD) is urgently needed. Clinical evidence consistently shows that higher dietary or biomarker levels of linoleic acid (LA; 18:2n6) reduce metabolic syndrome (Mets) and reduce the risk for CMD. Yet, dietary recommendations to include LA as part of a lifestyle plan with the goal of preventing CMD remain elusive.RECENT FINDINGS: Clinical interventions consistently show that dietary the addition of LA to the diet improves body composition, dyslipidemia, and insulin sensitivity while reducing systemic inflammation and fatty liver. These effects of LA position dietary LA-rich oils as a potential dietary strategy to aid in preventing CMD. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are cellular targets for many polyunsaturated fatty acids and oxylipin metabolites. PPAR activation can regulate dyslipidemia, insulin sensitivity, adipose biology, and inflammation, potentially explaining the plethora of effects of dietary LA on aspects of CMD.
    SUMMARY: Unraveling the cellular mechanism(s) of LA to impact PPAR activity may reset a false dogma that LA, as a member of the omega-6 fatty acid family, promotes inflammation in humans. In fact, LA appears to reduce inflammation and reduce risk for CMD.
    DOI:  https://doi.org/10.1097/MCO.0000000000000919
  6. Cell Rep Med. 2023 Mar 29. pii: S2666-3791(23)00099-X. [Epub ahead of print] 100993
    The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery.
    Panayiotis Louca, Abraham S Meijnikman, Ana Nogal, Francesco Asnicar, Ilias Attaye, Amrita Vijay, Afroditi Kouraki, Alessia Visconti, Kari Wong, Sarah E Berry, Emily R Leeming, Olatz Mompeo, Francesca Tettamanzi, Andrei-Florin Baleanu, Mario Falchi, George Hadjigeorgiou, Jonathan Wolf, Yair I Z Acherman, Arnold W Van de Laar, Victor E A Gerdes, Gregory A Michelotti, Paul W Franks, Nicola Segata, Massimo Mangino, Tim D Spector, William J Bulsiewicz, Max Nieuwdorp, Ana M Valdes, Cristina Menni.
      Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = -0.72, p = 1 × 10-5) and in response to fiber supplementation (β = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
    Keywords:  bariatric surgery; bile acids; liver function; post-prandial; triglycerides
    DOI:  https://doi.org/10.1016/j.xcrm.2023.100993
  7. J Biol Chem. 2023 Apr 05. pii: S0021-9258(23)00320-4. [Epub ahead of print] 104678
    Diet-induced induction of hepatic Serine/Threonine Kinase STK38 triggers proinflammation and hepatic lipid accumulation.
    Priya Rawat, Shilpa Thakur, Surbhi Dogra, Kajal Jaswal, Budheswar Dehury, Prosenjit Mondal.
      Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Although the involvement of chronic overnutrition, systemic inflammation, and insulin resistance in the development of NAFLD is well-established, however, the associations among these remain to be elucidated. Several studies have reported that chronic overnutrition, such as excessive consumption of fats (High Fat Diet, HFD) can cause insulin resistance and inflammation. However, the mechanisms by which HFD exerts inflammation and thereby promotes insulin resistance and intrahepatic fat accumulation remain poorly understood. Here, we show that HFD induces the expression of hepatic Serine/Threonine Kinase 38 (STK38), which further induces systemic inflammation leading to insulin resistance. Notably, Ectopic expression of STK38 in mouse liver leads to lean NAFLD phenotype with hepatic inflammation, insulin resistance, intrahepatic lipid accumulation, and hypertriglyceridemia in mice fed on a regular chow diet. Further, depletion of hepatic STK38 in HFD-fed mice remarkably reduces proinflammation, improves hepatic insulin sensitivity, and decreases hepatic fat accumulation. Mechanistically, two critical stimuli are elicited by STK38 action. For one stimulus, STK38 binds to Tank-Binding protein Kinase1 (TBK1) and induces TBK1 phosphorylation to promote NF-κβ nuclear translocation that mobilizes the release of pro-inflammatory cytokines and eventually leads to insulin resistance. The second, stimulus involves intrahepatic lipid accumulation by enhanced de novo lipogenesis via reducing the AMPK-ACC signaling axis. These findings identify STK38 as a novel nutrient-sensitive pro-inflammatory and lipogenic factor in maintaining hepatic energy homeostasis, and it provides a promising target for hepatic and immune health.
    Keywords:  High fat diet; STK38; TBK1; fatty liver; hepatic insulin resistance; inflammation
    DOI:  https://doi.org/10.1016/j.jbc.2023.104678
  8. J Gastrointestin Liver Dis. 2023 Apr 01. 32(1): 110-117
    Bile Composition - which Components Can Have Clinical Significance? A Review of the Literature.
    Paweł Bartłomiej Podgórski, Adam Przybyłkowski, Piotr Nehring.
      Over the years, scientific research concerning the qualitative analysis of bile and its use in diagnostics and treatment, have been very limited. Due to unsatisfactory results of detection, inter alia, cholangiocarcinoma or gallbladder carcinoma, and the necessity to discover more efficient techniques of diagnostics, bile has become an interesting direction to study. Nowadays, thanks to the latest research, analysis of concentration i.e. specific bile salts, proteins, nucleic or fatty acids in bile or imbalance of biliary microbiome, could play a crucial role in cancer detection or prognosis of progression such diseases as primary sclerosing cholangitis/ choledocholithiasis. This review article provides an overview of individual biliary solutes, which may play a role in diagnostics improvement.
    DOI:  https://doi.org/10.15403/jgld-4634
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