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Grb10a knockdown in Danio rerio during early life alters growth and cardiometabolic function associated with a remodelled transcriptome

ABSTRACT: Embryonic growth trajectory is a risk factor for chronic metabolic and cardiovascular disorders and influences birth weight and early post-natal weight gain in humans. Grb10 is a negative regulator of the main pathways driving embryonic growth. Grb10 knock-out in mammals increases insulin sensitivity and growth trajectory. This study has now investigated the long-term cardiometabolic consequences and associated transcriptomic profiles of morpholino induced early life disruption in grb10a expression in Danio rerio. Transient knockdown increased embryonic growth (+7 %) and metabolic rate (+25 %), while decreasing heart rate (-50 %) in early life. Juvenile growth and respiratory rate were also elevated (+30 % and 7-fold increase respectively). This was associated with permanent remodelling the transcriptional landscape. Multiple growth-related pathways were dysregulated. This study indicates that zebrafish are a suitable model for life-long investigation of the link between early growth and later life disease risk.

ORGANISM(S): Danio rerio

PROVIDER: GSE162474 | GEO | 2020/12/02

REPOSITORIES: GEO

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