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- W4380786096 abstract "Introduction: in liver, mitochondria continuously undergo biogenesis, fusion, fission and mitophagy, and thus participate to the regulation of energy metabolism, calcium homeostasis and lipid metabolism. Hypothesis: test the role of selective deletion of a key protein involved in inner mitochondrial membrane fusion (OPA1) in hepatocytes on mitochondrial function and lipid metabolism. Methods: liver selective OPA-1 deficient mice (Opa1LKO) were generated by crossing OPA-1 flox/flox mice with albumin-CRE+ mice. Opa1LKO and OPA1 flox/flox (controls) mice were fed a high fat diet for 20 weeks and then in vivo metabolic responses, liver and fat characteristics and proteomic signature were profiled. Results: Opa1LKO mice fed with HFD display reduced weight and weight gain compared to controls. Opa1LKO presented a significant reduction in fasting glycaemia as well as improved glucose tolerance and insulin tolerance compared to Opa1 WT. Moreover, plasma cholesterol levels and cholesterol distribution in lipoprotein fractions was reduced in Opa1LKO compared to Opa1 WT and the same was true for triglycerides. In vivo metabolic cages experiments revealed a reduced oxygen consumption and increased respiratory exchange rate in Opa1LKO compared to Opa1WT.Liver OPA1 deficiency limited lipid accumulation in the liver compared to Opa1 WT. Moreover, the liver from Opa1LKO mice presented an increased prevalence of smaller LD compared to Opa1 WT suggesting that diminished lipid accumulation and smaller LDs could be associated to changes in liver morphology and structure. In parallel Opa1LKO presented smaller adipocytes both in VAT and in SCAT compared to Opa1 WT. Interestingly, proteins involved in bile acids synthesis and transport were reduced in Opa1LKO liver compared to Opa1 WT, in parallel also proteins involved in lipoproteins uptake, lipoprotein synthesis (MTTP) and apolipoproteins (apoA-I, apoA2, apoB) were reduced. Conclusion: Our data suggest that the impairment of mitochondrial fusion could rewire liver metabolism and leads to cholestasis. This could be the consequence of altered bile acid synthesis, due to impaired mitochondrial activity, which results in reduced lipid absorption and limited liver lipid accumulation under HFD conditions." @default.
- W4380786096 created "2023-06-16" @default.
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- W4380786096 date "2022-11-08" @default.
- W4380786096 modified "2023-10-16" @default.
- W4380786096 title "Abstract 13968: The Alteration in Hepatic Inner Mitochondrial Membrane Fusion Affects Lipoprotein Metabolism and Liver Fat Accumulation" @default.
- W4380786096 doi "https://doi.org/10.1161/circ.146.suppl_1.13968" @default.
- W4380786096 hasPublicationYear "2022" @default.
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