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1.
Inn Med (Heidelb) ; 65(4): 347-356, 2024 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-38498179

RESUMEN

The etiology of primary sclerosing cholangitis (PSC) remains unclear, which explains in part the lack of a causal treatment. The differential diagnostic distinction from the even rarer immunoglobulin 4 (IgG4)-associated cholangitis (IAC) is becoming increasingly more successful. Advances in the understanding of different clinical courses, improvements in noninvasive diagnostics through modern magnetic resonance imaging (MRI) and the introduction of liver elastography have led to the development of improved prognostic models. The evidence for recommendations on medicinal (e.g., ursodeoxycholic acid) or endoscopic treatment (e.g., balloon dilatation and/or stent insertion) for PSC is still low. In contrast, the long-term results of liver transplantation in PSC patients are constantly improving. Due to the lack of highly sensitive and specific screening methods the early recognition of cholangiocellular carcinoma (CCC) as the most important complication is rarely successful. The continuous improvement of endoscopic retrograde cholangiopancreatography (ERCP) and direct cholangioscopy in combination with molecular biological and fluorescence in situ hybridization (FISH) analyses of bile duct tissue samples are promising for refined diagnostics. Due to the significantly increased risk of colorectal cancer, an annual colonoscopy is recommended in the presence of inflammatory bowel disease. Improvement of the early diagnostics of PSC and successful testing of new treatment strategies raise hope for a continuous improvement in the medical support of these complex patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangitis Esclerosante , Humanos , Colangitis Esclerosante/diagnóstico , Hibridación Fluorescente in Situ , Hígado/patología , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/diagnóstico
2.
Biochem Biophys Res Commun ; 692: 149342, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38061283

RESUMEN

Glucocorticoid synthesis typically occurs in adrenal cortex and is influenced by cholesterol balance, since cholesterol is the sole precursor of steroids. Bile acids as the signaling molecules, have been shown to promote steroidogenesis in steroidogenic cells. However, whether bile acids directly regulate cholesterol balance remains elusive. In this study, we prepared cholestatic mouse models and cultured human adrenocortical cells (H295R) treated with taurochenodeoxycholic acid (TCDCA) to determine transcription levels of cholesterol metabolism associated genes and cholesterol concentrations in adrenocortical cells. Results showed that common bile duct ligation (CBDL) and chenodeoxycholic acid (CDCA) feeding elevated the mRNA levels of Abca1, Cyp51, Hmgcr, Srb1, and Mc2r in adrenals of mice. Meanwhile, the concentrations of total cholesterol and cholesteryl ester in adrenals of CBDL and CDCA-fed mice were dramatically lowered. The total and phosphorylation levels of HSL in adrenal glands of CBDL mice were also enhanced. Similarly, TCDCA treatment in H295R cells decreased intracellular concentrations of total cholesterol and cholesteryl ester and increased transcription levels of SRB1, MC2R, and HSL as well. Inhibition of bile acids' receptor sphingosine 1-phosphate receptor 2 (S1PR2), extracellular signal-regulated kinase (ERK) phosphorylation, and steroidogenic factor 1 (SF-1) respectively successfully abolished effect of TCDCA on H295R cells. SF-1s was found to be phosphorylated at Thr75 in TCDCA-treated H295R cells. While a mild increase of intracellular cAMP concentration was detected upon TCDCA treatment, inhibition of PKA activity with Rp-Isomer in H295R cells failed to decrease the expression of SF-1 and its target genes. Our findings suggest that conjugated bile acids affect cholesterol balance through regulation of SF-1 in adrenocortical cells so as to provide an adequate cholesterol supply for glucocorticoid synthesis, which improves and enriches our understanding of the mechanism whereby bile acids regulate cholesterol balance to affect adrenal function.


Asunto(s)
Ácidos y Sales Biliares , Glucocorticoides , Humanos , Ratones , Animales , Factor Esteroidogénico 1/genética , Ésteres del Colesterol , Receptores de Esfingosina-1-Fosfato , Colesterol/metabolismo , Esteroides/metabolismo , Ácido Quenodesoxicólico , Ácido Tauroquenodesoxicólico
5.
Liver Int ; 43(9): 1975-1983, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37334864

RESUMEN

BACKGROUND & AIMS: On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier. METHODS: Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-ß-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease. RESULTS: Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3). DISCUSSION: We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.


Asunto(s)
Glucanos , beta-Glucanos , Humanos , Proyectos Piloto , Estudios Prospectivos , Cirrosis Hepática/complicaciones , Biomarcadores , Inflamación
6.
Wien Klin Wochenschr ; 135(Suppl 3): 493-523, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37358642

RESUMEN

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.


Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Austria , Consenso , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Hipertensión Portal/terapia , Hemorragia Gastrointestinal , Cirrosis Hepática
7.
Mol Cancer ; 22(1): 89, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37248468

RESUMEN

AIM: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. METHODS: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. RESULTS: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. CONCLUSIONS: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.


Asunto(s)
Neoplasias Colorrectales , Humanos , Oxaliplatino/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica
9.
Front Psychol ; 14: 1150548, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36968754

RESUMEN

Introduction: Although adherence to immunosuppressive medication is the key factor for long-term graft survival today, 20-70% of transplant recipients are non-adherent to their immunosuppressive medication. Objective: A prospective, randomized, controlled single-center feasibility study was designed to evaluate the impact of a step guided multicomponent interprofessional intervention program for patients after kidney or liver transplantation on adherence to their immunosuppressive medication in daily clinical practice. Materials and methods: The intervention consisted of group therapy and daily training as well as individual sessions in a step guided approach. The primary endpoint of the study was adherence to immunosuppression as assessed with the "Basel Assessment of Adherence to Immunosuppressive Medications Scale" (BAASIS). The coefficient of variation (CV%) of Tacrolimus (TAC) through levels and the level of personality functioning was a secondary endpoint. We conducted six monthly follow-up visits. Results: Forty-one age- and sex-matched patients [19 females, 58.5 (SD = 10.56) years old, 22 kidney- and 19 liver transplantation] were randomized to the intervention- (N = 21) or control-group (N = 20). No differences between intervention- and control groups were found in the primary endpoint adherence and CV% of TAC. However, in further exploratory analyses, we observed that individuals with higher impairments in personality functioning showed higher CV% of TAC in the controls. The intervention might compensate personality-related susceptibility to poor adherence as evident in CV% of TAC. Discussion: The results of the feasibility study showed that this intervention program was highly accepted in the clinical setting. The Intervention group could compensate higher CV% of TAC after liver or kidney transplantation in individuals with lower levels of personality functioning and non-adherence. Clinical trial registration: ClinicalTrials.gov, identifier NCT04207125.

12.
Gut ; 72(4): 607-608, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35764378
13.
Wien Klin Wochenschr ; 134(23-24): 875-882, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36369363

RESUMEN

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has affected liver disease management. The impact of the COVID-19 pandemic on the Austrian orthotopic liver transplantation (OLT) programs, however, has not been systematically investigated. METHODS: All patients listed for OLT in Austria during 2020-2021 were studied. Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, vaccinations, infections, mortality and the overall number of OLTs (vs. pre-COVID-19: 2015-2019) were analyzed. RESULTS: Overall, 490 patients (median age: 58.0 years, 70.4% men, hepatocellular carcinoma: 27.3%) were listed for OLT in Austria in 2020-2021. Alcohol-related cirrhosis (35.3%), cholestatic (16.7%) and viral liver disease (13.9%) were the main etiologies. Of the patients 61.2% underwent OLT and 8.8% died while on the waiting list. The number of OLTs performed during COVID-19 (2020: n = 150; 2021: n = 150) remained unchanged compared to pre-COVID-19 (median: n = 152). Among waiting list patients, 7.7% (n = 31/401) were diagnosed with COVID-19 and 7 (22.6%) of these patients died. By the end of 2021, 45.1% (n = 176/390; 82.8% mRNA vaccinations) and 28.8% (105/365) of patients received 2 and 3 SARS-CoV­2 vaccinations, respectively. After two SARS-CoV­2 vaccinations, antibodies more often remained undetectable in patients vaccinated post-OLT (25.6% vs. 6.5% in patients vaccinated pre-OLT; p = 0.034). Patients with three vaccinations after OLT had lower antibody titers than patients vaccinated pre-OLT (post-OLT: 513.5, IQR 44.4-2500.0 vs. pre-OLT: 2500.0, IQR 1462.0-2500.0 BAU/mL; p = 0.020). CONCLUSION: The number of OLTs in Austria remained unchanged during COVID-19. SARS-CoV­2 infections were rare but associated with high mortality in patients on the Austrian OLT waiting lists. SARS-CoV­2 vaccination rates at the end of 2021 were suboptimal, while serological response was better in patients vaccinated pre-OLT vs. post-OLT.


Asunto(s)
COVID-19 , Neoplasias Hepáticas , Trasplante de Hígado , Masculino , Humanos , Persona de Mediana Edad , Femenino , Pandemias , Austria/epidemiología , Vacunas contra la COVID-19 , COVID-19/epidemiología , SARS-CoV-2
14.
Respir Med ; 202: 106987, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36115317

RESUMEN

BACKGROUND & AIMS: Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. METHODS: We assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21-24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. RESULTS: Two-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50-60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. CONCLUSION: In chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.


Asunto(s)
Síndrome Hepatopulmonar , Hipertensión Pulmonar , Enfermedades Pulmonares , Hipertensión Arterial Pulmonar , Enfermedades Vasculares , Hemodinámica , Síndrome Hepatopulmonar/diagnóstico , Síndrome Hepatopulmonar/epidemiología , Síndrome Hepatopulmonar/etiología , Humanos , Hipertensión Pulmonar/etiología , Cirrosis Hepática/complicaciones , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Oxígeno , Enfermedades Vasculares/complicaciones
15.
Dtsch Med Wochenschr ; 147(18): 1199-1212, 2022 09.
Artículo en Alemán | MEDLINE | ID: mdl-36070738

RESUMEN

Immunosuppression is an essential prerequisite for successful transplantation. In order to reduce the sometimes-considerable side effects, combination therapies with different agents are used. This article aims to provide an up-to-date overview of immunosuppression after liver and kidney transplantation.


Asunto(s)
Trasplante de Riñón , Trasplante de Órganos , Humanos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Trasplante de Órganos/efectos adversos
17.
Eur J Neurol ; 29(8): 2283-2288, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35485970

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease and particularly liver fibrosis are related to cardiovascular disease and may indicate an increased risk for atrial fibrillation (AF), but this association has not yet been systematically investigated in a cohort of ischemic stroke patients. METHODS: We analyzed data from a prospective single-center study enrolling all consecutive ischemic stroke patients admitted to our stroke unit over a 1-year period. All patients received a thorough etiological workup. For evaluation of liver fibrosis, we determined the Fibrosis-4 (FIB-4) index, a well-established noninvasive liver fibrosis test. Laboratory results were analyzed from a uniform blood sample taken at stroke unit admission. RESULTS: Of 414 included patients (mean age 70.2 years, 57.7% male), FIB-4 indicated advanced liver fibrosis in 92 (22.2%). AF as the underlying stroke mechanism was present in 28.0% (large vessel disease: 25.6%, small vessel disease: 11.4%, cryptogenic: 29.2%). Patients with FIB-4 ≥ 2.67 had higher rates of AF (53.3% vs. 20.8%, p < 0.001), and this association remained significant after correction for established AF risk factors (odds ratio 2.53, 95% confidence interval 1.44-4.46, p = 0.001). FIB-4 was further associated with worse functional outcome 3 months (p < 0.001) and higher mortality 4 years post-stroke (p < 0.02), but these relationships were no longer present after correction for age and initial stroke severity. Moreover, FIB-4 was not associated with long-term recurrent vascular events. CONCLUSIONS: Liver fibrosis assessed by the FIB-4 index is independently associated with AF in acute ischemic stroke patients. Further studies should evaluate whether adding the FIB-4 index to AF risk scores increases their precision.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Masculino , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología
18.
Liver Int ; 42(8): 1849-1860, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35261130

RESUMEN

BACKGROUND AND AIMS: The high risk for severe shunting-related post-interventional complications demands a stringent selection of candidates for transjugular intrahepatic portosystemic shunt (TIPS). We aimed to develop a simple and reliable tool to accurately predict early post-TIPS mortality. METHODS: 144 cases of TIPS implantation were retrospectively analysed. Using univariate and multivariate Cox regression analysis of factors predicting mortality within 90 days after TIPS, a score integrating urea, international normalized ratio (INR) and bilirubin was developed. The Modified TIPS-Score (MOTS) ranges from 0 to 3 points: INR >1.6, urea >71 mg/dl and bilirubin >2.2 mg/dl account for one point each. Additionally, MOTS was tested in an external validation cohort (n = 187) and its performance was compared to existing models. RESULTS: Modified TIPS-Score achieved a significant prognostic discrimination reflected by 90-day mortality of 8% in patients with MOTS 0-1 and 60% in patients with MOTS 2-3 (p < .001). Predictive performance (area under the curve) of MOTS was accurate (c = 0.845 [0.73-0.96], p < .001), also in patients with renal insufficiency (c = 0.830 [0.64-1.00], p = .02) and in patients with refractory ascites (c = 0.949 [0.88-1.00], p < .001), which are subgroups with particular room for improvement of post-TIPS mortality prediction. The results were reproducible in the validation cohort. CONCLUSIONS: Modified TIPS-Score is a novel, practicable tool to predict post-TIPS mortality, that can significantly simplify clinical decision making. Its practical applicability should be further investigated.


Asunto(s)
Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Ascitis/complicaciones , Bilirrubina , Encefalopatía Hepática/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Urea
19.
BMC Gastroenterol ; 21(1): 460, 2021 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876016

RESUMEN

BACKGROUND: Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis. METHODS: Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry. RESULTS: Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels. CONCLUSIONS: We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.


Asunto(s)
Colestasis , Síndrome de Cushing , Animales , Colestasis/complicaciones , Síndrome de Cushing/complicaciones , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Ratones , Sistema Hipófiso-Suprarrenal , Índice de Severidad de la Enfermedad
20.
Cells ; 10(10)2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34685599

RESUMEN

Lysosomal acid lipase (LAL) is the sole enzyme known to be responsible for the hydrolysis of cholesteryl esters and triglycerides at an acidic pH in lysosomes, resulting in the release of unesterified cholesterol and free fatty acids. However, the role of LAL in diet-induced adaptations is largely unexplored. In this study, we demonstrate that feeding a Western-type diet to Lal-deficient (LAL-KO) mice triggers metabolic reprogramming that modulates gut-liver cholesterol homeostasis. Induction of ileal fibroblast growth factor 15 (three-fold), absence of hepatic cholesterol 7α-hydroxylase expression, and activation of the ERK phosphorylation cascade results in altered bile acid composition, substantial changes in the gut microbiome, reduced nutrient absorption by 40%, and two-fold increased fecal lipid excretion in LAL-KO mice. These metabolic adaptations lead to impaired bile acid synthesis, lipoprotein uptake, and cholesterol absorption and ultimately to the resistance of LAL-KO mice to diet-induced obesity. Our results indicate that LAL-derived lipolytic products might be important metabolic effectors in the maintenance of whole-body lipid homeostasis.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Disbiosis/metabolismo , Metabolismo de los Lípidos , Obesidad/metabolismo , Esterol Esterasa/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Esterol Esterasa/genética
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