RT Journal Article
T1 Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.
A1 Opazo-Rios, Lucas
A1 Soto-Catalan, Manuel
A1 Lazaro, Iolanda
A1 Sala-Vila, Aleix
A1 Jimenez-Castilla, Luna
A1 Orejudo, Macarena
A1 Moreno, Juan Antonio
A1 Egido, Jesus
A1 Mas-Fontao, Sebastian
K1 BTBR ob/ob
K1 De novo lipogenesis
K1 Meta-inflammation
K1 Metabolic associated fatty liver disease
AB Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.
PB MDPI
YR 2022
FD 2022-03-30
LK http://hdl.handle.net/10668/21148
UL http://hdl.handle.net/10668/21148
LA en
NO Opazo-Ríos L, Soto-Catalán M, Lázaro I, Sala-Vila A, Jiménez-Castilla L, Orejudo M, et al. Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice. Int J Mol Sci. 2022 Apr 2;23(7):3965
DS RISalud
RD Apr 8, 2025