Abstract:
BACKGROUND & AIMS:High-carbohydrate diets contribute to the development of liver stress and fatty liver disease. While saturated fatty acids are known to induce liver stress, the role of monounsaturated fatty acids (MUFA), synthesized by the stearoyl-CoA desaturase (SCD) family of enzymes, in regulation of liver function during lipogenic dietary conditions remains largely unknown. The major products of SCD-catalyzed reactions are oleate (18:1n-9) and palmitoleate (16:1n-7). METHODS:We generated mouse models with restricted exogenous MUFA supply and reduced endogenous MUFA synthesis, in which SCD1 global knockout (GKO) or liver-specific knockout (LKO) mice were fed a lipogenic high-sucrose very low-fat (HSVLF) or high-carbohydrate (HC) diet. In a gain-of-function context, we introduced liver-specific expression of either human SCD5, which synthesizes 18:1n-9, or mouse Scd3, which synthesizes 16:1n-7, into SCD1 GKO mice and fed the HSVLF diet. RESULTS:Lipogenic high-carbohydrate diets induced hepatic endoplasmic reticulum (ER) stress and inflammation in SCD1 GKO and LKO mice. Dietary supplementation with 18:1n-9, but not 18:0, prevented the HSVLF diet-induced hepatic ER stress and inflammation in SCD1 LKO mice, while hepatic SCD5, but not Scd3, expression reduced the ER stress and inflammation in GKO mice. Additional experiments revealed liver-specific deletion of the transcriptional coactivator PGC-1α reduced hepatic inflammatory and ER stress response gene expression in SCD1 LKO mice. CONCLUSIONS:Our results demonstrate an indispensable role of hepatic oleate in protection against lipogenic diet-induced hepatic injury, and PGC-1α potentiates the ER stress response under conditions of restricted dietary oleate coupled to reduced capacity of endogenous hepatic oleate synthesis. LAY SUMMARY:Susceptibility to metabolic dysfunction is influenced by genetic and environmental factors. In this study we show that modulation of two genes regulates the liver response, including ER stress and inflammation, to a high-carbohydrate low-fat diet. We reveal that hepatic availability of oleate, a monounsaturated fatty acid, is important for maintenance of liver health.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Liu X,Burhans MS,Flowers MT,Ntambi JMdoi
10.1016/j.jhep.2016.03.001subject
Has Abstractpub_date
2016-07-01 00:00:00pages
103-112issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(16)30028-9journal_volume
65pub_type
杂志文章abstract:BACKGROUND & AIMS:To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b (PEG-IFN) and ribavirin (RBV) in patients with chronic hepatitis C. METHODS:In a multi-center randomized clinical trial in Japan, on patients infected with HCV of genotype 1, 126 patients were assigned to telaprev...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2011.07.016
更新日期:2012-01-01 00:00:00
abstract::Porphyria cutanea tarda (PCT) is a metabolic disorder characterized by a reduced hepatic activity of uroporphynogen decarboxylase (URO-D), an enzyme of the heme synthesis. The clinical features of PCT may be brought into light by hepatic injury induced by hepatitis C virus (HCV). A significant association between HCV ...
journal_title:Journal of hepatology
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doi:10.1016/j.jhep.2004.10.029
更新日期:2005-04-01 00:00:00
abstract::The mechanism responsible for liver cell necrosis in patients with hepatitis A is not known. Since the type of hepatic lesions and the clinical presentation of acute hepatitis B are similar and are probably related to the cell-mediated immune response to a viral antigen located in the liver cell, it is possible that a...
journal_title:Journal of hepatology
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doi:10.1016/s0168-8278(86)80082-4
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND/AIM:The aim of this study was to assess the pathology and pathogenic mechanisms involved in the occlusion of transjugular intrahepatic portosystemic stent-shunts. METHODS:Thirty-four patients with transjugular intrahepatic portosystemic stent-shunt who had at least two portographic assessments of shunt func...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(96)80026-2
更新日期:1996-02-01 00:00:00
abstract::We report a novel method to assess bile secretory pressure using a Statham pressure transducer. The studies were performed in vivo in male Sprague-Dawley rats under pentobarbital anesthesia. Maximal secretory pressure averaged 21.8 +/- 1.1 (S.D.) cmH2O. The bile accumulated after 10 min of obstruction was 7.7 +/- 2.8 ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90156-6
更新日期:1989-01-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. Increasing recognition of the importance of NAFLD and its association with the features of the metabolic syndrome has stimulated an interest in its putative role in the development and progression of chronic kidney dise...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2010.11.007
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND & AIMS:It is established that cirrhotic patients who respond to beta-blockers by lowering their hepatic venous pressure gradient (HVPG) to < or =12 mmHg or by > or =20% of the baseline values are protected from bleeding. However, it is not known whether the effect remains unchanged over the treatment period....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.10.014
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis B virus (HBV) infection was hyperendemic in Taiwan before the implementation of the universal infant hepatitis B immunization program, which was launched in 1984. Five previous seroepidemiologic surveys were conducted at 0, 5, 10, 15, and 20 years after the launch of the vaccination program....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.05.021
更新日期:2012-10-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80306-0
更新日期:1996-12-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章
doi:10.1016/s0168-8278(98)80275-4
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND/AIMS:The molecules involved in the progression of hepatocellular carcinoma (HCC) are not fully understood. The aim of this study was to elucidate the crucial genes involved in cancer progression and metastasis. METHODS:Selectively expressed genes were screened using differential display analysis, and then f...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00183-0
更新日期:2001-11-01 00:00:00
abstract::The prognostic value of portal hemodynamics, measured by pulsed echo-Doppler, was prospectively evaluated, together with clinical, biochemical and endoscopic parameters, in a series of 50 consecutive patients with compensated cirrhosis. After a mean follow-up of 6 years, 25 patients had died, all from complications of...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80521-5
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND & AIMS:The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this stu...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2017.01.020
更新日期:2017-06-01 00:00:00
abstract::It has been suggested that the cellular immune response to HBV antigens is responsible for hepatocellular injury in acute and chronic hepatitis B. However, definitive immunological studies have so far been hampered by the lack of appropriate model systems to study HBV antigen-specific T cells. The availability of high...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/s0168-8278(88)80503-8
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND/AIMS:Graft reperfusion in liver transplantation is usually performed by initial portal reperfusion (IPR) and delayed rearterialization. Its influence on graft microcirculation is unknown. This study aimed to assess sinusoidal perfusion in dependence to this reperfusion technique during human living-donor liv...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2004.04.017
更新日期:2004-08-01 00:00:00
abstract::The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(87)80004-1
更新日期:1987-02-01 00:00:00
abstract::Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver transplantation (ELT) is an es...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.12.016
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND/AIMS:The efficacy and safety of rifaximin in comparison with lactitol in the treatment of acute hepatic encephalopathy was assessed in a prospective randomized, double-blind, double-dummy, controlled trial. METHODS:A total of 103 patients with grade I-III acute hepatic encephalopathy were randomized to rece...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-01-01 00:00:00
abstract:BACKGROUND/AIMS:Adrenomedullin recently discovered in human pheochromocytoma is a potent vasodilatory peptide mainly derived from vascular endothelial and smooth muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation, has been attributed to peripheral vasodilatation in liver cirrhosis. However,...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80235-3
更新日期:1998-05-01 00:00:00
abstract::The multidrug resistance genes encode plasma membrane glycoproteins named P-glycoproteins, that act as an ATP-dependent drug efflux pump and decrease the cytosolic concentration of chemotherapeutic agents. It has been hypothesized that in rat liver, this protein may have a physiological role as a biliary transporter o...
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pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80235-1
更新日期:1994-11-01 00:00:00
abstract::The activation of protein kinase C (PKC) has been implicated in the pathogenesis of gram-negative sepsis. The effects of PKC modulation on hepatic flow and metabolism were studied using isolated liver perfusion. The liver was isolated from well-fed or overnight-fasted, male Sprague-Dawley rats weighing 250-310 g, and ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80561-6
更新日期:1993-11-01 00:00:00
abstract::A patient with evidence of chronic infection with hepatitis B virus (seropositive for hepatitis B surface antigen, and with antibody to hepatitis B e antigen) underwent renal transplantation, which subsequently failed. The patient developed abnormal liver function tests and 8 months after the removal of the transplant...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(95)80116-2
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND/AIMS:Results of our previous studies supported the concept that in the human liver, the smallest ramification of the biliary tree, the bile ductules, might contain hepatic progenitor cells. An insufficient proliferative response and loss of bile ductules preceded bile duct loss whereas preservation of bile d...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.03.015
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND/AIMS:Reactive oxygen species, proinflammatory cytokines, glutathione depletion and nitric oxide have all been implicated in the pathogenesis of fulminant hepatic failure. The aim of the present study was to examine the respective roles of these factors in the pathogenesis of thioacetamide-induced fulminant h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80160-3
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND/AIMS:The aim of the study was to investigate the effect of a standard albumin load on blood volume distribution, arterial compliance, and the renin-angiotensin-aldosterone system in patients with different degrees of cirrhosis. METHODS:31 patients with cirrhosis (Child classes A/B/C=8/14/9) received an intr...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00160-0
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND/AIMS:Protein-L-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIM...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.026
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND & AIMS:Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to im...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.07.018
更新日期:2018-11-01 00:00:00
abstract::Human serum albumin (HSA) is one of the most frequent treatments in patients with decompensated cirrhosis. Prevention of paracentesis-induced circulatory dysfunction, prevention of type-1 HRS associated with bacterial infections, and treatment of type-1 hepatorenal syndrome are the main indications. In these indicatio...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2014.04.012
更新日期:2014-08-01 00:00:00
abstract::The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the ...
journal_title:Journal of hepatology
pub_type:
doi:10.1016/j.jhep.2014.05.016
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND/AIMS:Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS:A total of 151 patients r...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(99)80214-1
更新日期:1999-08-01 00:00:00