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- W4302016072 abstract "ABSTRACT There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ 42 ) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ 42 , which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ 42 . Increasing circulating Aβ 42 levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ 40 isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ 42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ 42 inhibited mitochondrial function. These data reveal a role for systemic Aβ 42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure." @default.
- W4302016072 created "2022-10-06" @default.
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- W4302016072 date "2022-10-05" @default.
- W4302016072 modified "2023-09-25" @default.
- W4302016072 title "Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity" @default.
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- W4302016072 doi "https://doi.org/10.1101/2022.10.02.510555" @default.
- W4302016072 hasPublicationYear "2022" @default.
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