Hepatic steatosis in the mouse model of wilson disease coincides with a muted inflammatory response

Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histology, hepatic proteome, and Cu content were analyzed. Wild-type and Atp7b-/- livers showed striking similarities in their responses to Western diet, most notably down-regulation of cholesterol biosynthesis, altered nuclear receptor signaling, and changes in cytoskeleton. Western diet increased body fat content and induced liver steatosis in males and females regardless of genotype, however the effects were less pronounced in Atp7b-/- mice compared to wild-type. Although hepatic Cu remained elevated in Atp7b-/- mice, liver inflammation was reduced. The diet diminished signaling by Rho GTPases, integrin, IL8, and reversed changes in cell cycle machinery and cytoskeleton. Overall, high calories decreased inflammatory response in favor of steatosis without improving markers of cell viability. Similar changes of cellular pathways during steatosis development in wil...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research

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Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research
Am J Pathol. 2021 Oct 7:S0002-9440(21)00435-1. doi: 10.1016/j.ajpath.2021.09.010. Online ahead of print.ABSTRACTWilson disease (WND) is caused by inactivation of the copper (Cu) transporter ATP7B and Cu accumulation in tissues. WND presentations vary from liver steatosis to inflammation, fibrosis, and liver failure. Diets influence the liver phenotype in WND, but findings are inconsistent. To better understand the impact of excess calories on liver phenotype in WND, we compared C57BL/6J Atp7b-/- and C57BL/6J mice fed for 12 weeks with Western diet or normal chow. Serum and liver metabolites, body fat content, liver histolo...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research
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