Basic–Liver, Pancreas, and Biliary TractActivation and Dysregulation of the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease
Section snippets
Study Cohort
Consecutive subjects who were referred for either obesity management or suspected NAFLD were screened for this study. All subjects underwent routine clinical assessment and radiologic, hematologic, biochemical, and serologic testing. The metabolic syndrome was diagnosed using the Adult Treatment Panel III criteria.19 Alcohol consumption was assessed clinically and considered to be significant when >20 g/day for females and >30 g/day for males. All subjects were tested for hepatitis B and C,
Results
A total of 89 subjects were screened: 59 subjects were enrolled (controls [normal histology + normal ALT] = 17, NAFL = 21, and NASH = 21). The reasons for exclusion included refusal to consent (n = 17), insufficient amount of tissue for experimental studies (n = 9), and alanine aminotransferse (ALT) elevation in those with normal histology (n = 4). The baseline characteristics of the study population are shown in Table 2. The 3 groups were comparable with respect to gender, ethnicity, and
Discussion
The delicate balance between a cell’s synthetic needs and the ability of the ER to meet these demands is an important determinant of whether a given cell lives or dies. Perturbation of this balance triggers the UPR, which can either correct the imbalance and help the cell adapt or condemns the cell to death.6 In this study, we demonstrate that there is activation of the UPR in both NAFL and NASH. However, NASH is distinguished from NAFL subjects and controls with the metabolic syndrome and
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Cited by (0)
Supported in part by grants K24 DK 02755-07, T32 DK 007150-32, and RO1 56331 (to A.J.S.) from the National Institutes of Health.
This work was fully approved by the IRB of the VCU Medical Center (IRB No. 04286).
No conflicts of interest exist.