Effect of high fat diet on the rat germ cell transcriptome

PURPOSE: To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, and alters the germ cell (GC) transcriptome. PROCEDURE: GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). After metabolic testing, founders (F0) were bred with controls, establishing the F1 generation. Germ cells from F0 males were isolated and their RNA sequenced. F1 rats were bred with control rats at 17 weeks to generate F2 offspring. FINDINGS: HFD resulted in 9.7% and 14.7% increased weight in male and female F0 respectively. F1 offspring of HFD mothers were heavier than controls. F1 daughters of HFD-fed males were also heavier. F2 male offspring derived from HFD-fed maternal grandfathers were 7.2% heavier, and exhibited increases of 31% in adiposity, 97% in plasma leptin and 300% in luteinising hormone to testosterone ratio. HFD exposure did not alter the F0 GC transcriptome. CONTROLS: Matched CD was consumed by all animals not consuming the HFD. Animals were compared to a parallel cohort of CD rats. CONCLUSIONS: HFD consumption by maternal grandfathers results in a disrupted metabolic phenotype in grandsons. This effect is not mediated by alterations to the GC transcriptome. Overall design: Male rats high fat diet vs. control diet. 4 replicates per condition. SmallRNA seq and mRNAseq for each replicate and condition

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Chambers TJG, Morgan MD, Heger AH, Sharpe RM, Drake AJ