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The Propensity of t...
The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity
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Ferri, F. (författare)
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Carotti, S. (författare)
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Carpino, G. (författare)
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Mischitelli, M. (författare)
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Cantafora, A. (författare)
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- Molinaro, Antonio (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Argenziano, M. E. (författare)
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Parisse, S. (författare)
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Corsi, A. (författare)
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Riminucci, M. (författare)
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Lai, Q. (författare)
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Mennini, G. (författare)
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Spadetta, G. (författare)
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Pugliese, F. (författare)
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Rossi, M. (författare)
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Morini, S. (författare)
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Gaudio, E. (författare)
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Corradini, S. G. (författare)
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(creator_code:org_t)
- 2021-06-05
- 2021
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:11
- Relaterad länk:
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https://www.mdpi.com...
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving >= 50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by alpha-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- cholesterol
- liver donor
- hepatic stellate cells
- fibrosis
- large
- droplet macrovesicular steatosis
- lipid droplets
- INSIG-1
- NAFLD
- PNPLA3
- donor graft steatosis
- hepatitis-c virus
- nonalcoholic steatohepatitis
- triglyceride
- disease
- protein
- gene
- transcription
- pathology
- pattern
- Biochemistry & Molecular Biology
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Ferri, F.
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Carotti, S.
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Carpino, G.
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Mischitelli, M.
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Cantafora, A.
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Molinaro, Antoni ...
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visa fler...
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Argenziano, M. E ...
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Parisse, S.
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Corsi, A.
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Riminucci, M.
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Lai, Q.
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Mennini, G.
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Spadetta, G.
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Pugliese, F.
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Rossi, M.
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Morini, S.
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Gaudio, E.
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Corradini, S. G.
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visa färre...
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