Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA882101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21629033.fastq.gz | Fastqsanger.gz | |||
| SRR21629034.fastq.gz | Fastqsanger.gz | |||
| SRR21629035.fastq.gz | Fastqsanger.gz | |||
| SRR21629036.fastq.gz | Fastqsanger.gz | |||
| SRR21629037.fastq.gz | Fastqsanger.gz |
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Project description: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 (Ab42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Ab42, which is increased from adipose tissue of obese mice and is associated with higher plasma Ab42. Increasing circulating Ab42 levels in 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 Ab40 levels were increased. Administration of an Ab neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Ab neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Ab42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Ab42 inhibited mitochondrial function. These data reveal a role for systemic Ab42 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.
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Project description:Two carrier-free peptides were synthesized and used in experiments: amyloid beta 42 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA), and a scrambled variant with the same chemical constituency as amyloid beta 42 (AIAEGDSHVLKEGAYMEIFDVQGHVFGGKIFRVVDLGSHNVA). To perform blockade current measurements, first, the sub-nanopore was wetted by immersion in de-gassed 250 mM NaCl electrolyte for 1-3 days. Subsequently, to measure the blockade current, a transmembrane voltage bias (< 700 mV) was applied to the reservoir relative to the ground in the channel using Ag/AgCl electrodes and the corresponding pore current was measured using either an Axopatch 700B or an Axopatch 200B amplifier with an open bandwidth. The actual bandwidth was inferred from the rise-time to a sharp (10 ps rise-time) input pulse to be about 75 kHz to 100 kHz, depending on the amplifier and the feedback. The analog data were digitized by a 16-bit DigiData 1550B data acquisition system (DAQ, Molecular Devices, Sunnyvale, CA) at a sampling rate of 500 kS/s and recorded in 3 minute-long acquisition windows. A total of 12 Axon binary files (ABF) were collected for amyloid beta 42, and 71 ABF files for scrambled amyloid beta 42.
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