Weight reduction through a low fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice
BackgroundTo examine the circulating microRNA (miRNA) expression profile in a mouse model of diet induced obesity (DIO) with subsequent weight reduction achieved via low fat diet (LFD) feeding.ResultsEighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN 76A (fat: 11.5 kcal diet for 12 weeks; (2) DIO, mice were fed a 58 kcal high fat diet (HFD) for 12 weeks; and (3) DIO LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal LFD for 4 weeks. A switch to LFD feeding led to decreases in body weight, adiposity, and blood glucose levels in DIO mice. Microarray analysis of miRNA using The Mouse Rat miRNA OneArray(r) v4 system revealed significant alterations in the expression of miRNAs in DIO and DIO LFD mice. Notably, 23 circulating miRNAs (mmu miR 16, mmu let 7i, mmu miR 26a, mmu miR 17, mmu miR 107, mmu miR 195, mmu miR 20a, mmu miR 25, mmu miR 15b, mmu miR 15a, mmu let 7b, mmu let 7a, mmu let 7c, mmu miR 103, mmu let 7f, mmu miR 106a, mmu miR 106b, mmu miR 93, mmu miR 23b, mmu miR 21, mmu miR 30b, mmu miR 221, and mmu miR 19b) were significantly downregulated in DIO mice but upregulated in DIO LFD mice. Target prediction and function annotation of associated genes revealed that these genes were predominantly involved in metabolic, insulin signaling, and adipocytokine signaling pathways that directly link the pathophysiological changes associated with obesity and weight reduction.ConclusionsThese results imply that obesity related reductions in the expression of circulating miRNAs could be reversed through changes in metabolism associated with weight reduction achieved through LFD feeding.
BMC Genomics