Non‐alcoholic fatty liver disease proteomics

Rodríguez-Suárez, Eva; Duce, Antonio Martín; Caballería, Juan; Arrieta, Felix; Fernández, Estefanía; Gómara, Carolina; Alkorta, Nere; Ariz, Usue; Martínez‐Chantar, María Luz; Lu, Shelly C.; Elortza, Félix; Mato, José M.

doi:10.1002/prca.200900119

Cited by 54 publications

(59 citation statements)

References 50 publications

(55 reference statements)

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“…The ASS gene products were not changed and thus were not rate limiting in NASH. The changes in CPS enzyme protein are in accordance with a recent study on proteomics in human NAFLD in which CPS in liver samples from patients with NASH was found to be downregulated (33).…”

Section: Discussionsupporting

confidence: 89%

Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function

Thomsen

Grønbæk

Glavind

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its consequences for liver function are unknown. We studied ureagenesis, an essential metabolic liver function of importance for whole body nitrogen homeostasis, in a rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol diet for 4 and 16 wk, resulting in early and advanced experimental NASH, respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS remained unchanged. Advanced NASH further decreased the carbamoyl phosphate synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65 ± 0.23 to 4.58 ± 0.30 μmol × (min × 100 g)(-1); P = 0.01]. Early NASH compromised the genes and enzyme proteins involved in ureagenesis, whereas advanced NASH resulted in a functional reduction in the capacity for ureagenesis. The pattern of urea cycle perturbations suggests a prevailing mitochondrial impairment by NASH. The decrease in CUNS has consequences for the ability of the body to adjust to changes in the requirements for nitrogen homeostasis e.g., at stressful events. NASH, thus, in terms of metabolic consequences, is not an innocuous lesion, and the manifestations of the damage seem to be a continuum with increasing disease severity.

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Section: Discussionsupporting

confidence: 89%

Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function

Thomsen

Grønbæk

Glavind

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Rodríguez-Suárez et al [24] analysed the protein expression of liver samples with DIGE in combination with MALDI TOF/TOF. Ten of the proteins were further validated by Western blotting to confirm the observed changes of protein expression [24] .…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

“…Ten of the proteins were further validated by Western blotting to confirm the observed changes of protein expression [24] . This study has successfully demonstrated that both serum concentration of carbamoyl phosphate synthase 1 (CPS1) and 78 kDa glucose-regulated protein (GRP78) decreased gradually from cholecystectomy controls with normal liver function and histology subjects to steatosis and NASH patients [24] . Further validation of CPS1 and GRP78 in higher number of patients is still warranted.…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

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Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Lim

Dillon

Miller

2014

WJG

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Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) antiinflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. Key words: Non-alcoholic fatty liver disease; Proteomics; Genomics; Metabolic syndrome; Pathophysiology Core tip: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder in Western populations. NAFLD can occur as a spectrum diseases, from simple steatosis, to non-alcoholic steatohepatitis characterised by hepatocellular injury and inflammation, to cirrhosis and hepatocellular carcinoma. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. This review highlighted several functional proteins and genetic polymoprhisms; particular those involved in insulin resistance, triglycerides metabolism and hepatic inflammation. It is hoped that this review will offer further insights into the pathophysiology of NAFLD.

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“…In order to identify new biomarkers, Rodríguez-Suárez and colleagues performed protein expressions of liver biopsies in three groups of subjects that included controls and patients with either NAFLD or non-alcoholic steatohepatitis (NASH). The liver samples were analyzed using two-dimensional differential gel electrophoresis (DIGE) combined with MALDI TOF/TOF analysis [93]. A total of 43 proteins exhibiting significant differential expression was identified, including 22 comparing steatosis samples versus controls, and 21 comparing NASH versus controls.…”

Section: Proteomics Examplementioning

confidence: 99%