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Publication
Inflammation and Ectopic Fat Deposition in the Aging Murine Liver Is Influenced
by CCR2.
Authors Stahl EC, Delgado ER, Alencastro F, LoPresti ST, Wilkinson PD, Roy N, Haschak
MJ, Skillen CD, Monga SP, Duncan AW, Brown BN
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal The American journal of pathology
Year 2020
Date Published 2/1/2020
Volume : Pages 190 : 372 - 387
PubMed Reference 31843499
Abstract Aging is associated with inflammation and metabolic syndrome, which manifests in
the liver as nonalcoholic fatty liver disease (NAFLD). NAFLD can range in
severity from steatosis to fibrotic steatohepatitis and is a major cause of
hepatic morbidity. However, the pathogenesis of NAFLD in naturally aged animals
is unclear. Herein, we performed a comprehensive study of lipid content and
inflammatory signature of livers in 19-month-old aged female mice. These animals
exhibited increased body and liver weight, hepatic triglycerides, and
inflammatory gene expression compared with 3-month-old young controls. The aged
mice also had a significant increase in F4/80+ hepatic macrophages, which
coexpressed CD11b, suggesting a circulating monocyte origin. A global knockout
of the receptor for monocyte chemoattractant protein (CCR2) prevented excess
steatosis and inflammation in aging livers but did not reduce the number of
CD11b+ macrophages, suggesting changes in macrophage accumulation precede or are
independent from chemokine (C-C motif) ligand-CCR2 signaling in the development
of age-related NAFLD. RNA sequencing further elucidated complex changes in
inflammatory and metabolic gene expression in the aging liver. In conclusion, we
report a previously unknown accumulation of CD11b+ macrophages in aged livers
with robust inflammatory and metabolic transcriptomic changes. A better
understanding of the hallmarks of aging in the liver will be crucial in the
development of preventive measures and treatments for end-stage liver disease in
elderly patients.





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