RNA-sequencing analysis of paternal low-protein diet-induced gene expression change in mouse offspring adipocytes

Increasing evidence indicates that parental diet affects the metabolism and health of offspring. It is reported that paternal low-protein diet (pLPD) induces glucose intolerance and the expression of genes involved in cholesterol biosynthesis in mouse offspring liver. The aim of the present study was to determine the effect of a pLPD on gene expression in offspring white adipose tissue (WAT), another important tissue for the regulation of metabolism. RNA-seq analysis indicated that pLPD up- and down-regulated 54 and 274 genes, respectively, in offspring WAT,. The mRNA expression of many genes involved in lipogenesis was down-regulated by pLPD feeding, which may contribute to glucose intolerance. The expression of carbohydrate response element-binding protein ß (ChREBP-ß), an important lipogenic transcription factor, was also significantly lower in the WAT of pLPD offspring, which may have mediated the down-regulation of the lipogenic genes. By contrast, the LPD did not affect the expression of lipogenic genes in the WAT of the male progenitor, but increased the expression of lipid oxidation genes, suggesting that a LPD reduces WAT mass by activating lipid oxidation, and that LPD may reduce WAT mass using differing mechanisms in parents and offspring. These findings add to our understanding of how paternal diet can regulate metabolism in their offspring. Overall design: iWAT mRNA profiles of 10-12-week old wild type male mice fed control diet (CD) and low-protein diet (LPD) (F0 generation), in duplicate; iWAT mRNA profiles of 5-week old wild type (WT) male offspring (F1 generation) from father mice fed CD and LPD were generated by deep sequencing, in triplicate, using NextSeq500 Illumina.