High fat diet impacts lipid metabolism by altering the transportation, oxidation, and storage of fatty acids. Lipoprotein lipase (LPL) plays a critical role in lipid metabolism by catalyzing triglyceride hydrolysis and lipoprotein uptake in multiple tissues. A previous study reported that miR-29b negatively regulated LPL expression in mammary epithelial cells transfected with miR-29b mimics. The present study investigated changes in LPL expression and epigenetic mechanisms by the miR-29 family in different tissues in mice fed a high fat diet. Five-week old male CBA mice were fed with either a control diet (Con group, 10% kcal from fat) or a high fat diet (HF group, 45% kcal from fat) ad libitum for 11 weeks. The results showed that LPL mRNA was increased in adipose, muscle and colon in response to high fat diet. However, LPL mRNA expression decreased in the liver by high fat diet as well as hepatic lipase (HL). The results also showed the highest expression level of LPL mRNA in adipose tissue, followed by muscle, colon, and liver. Meanwhile, high fat diet reduced the expression of miR-29a/b, predicted suppressors of LPL from miR-29 family, in adipose tissue. Genomic analysis predicted several potential transcription factors of miR-29 family members that suppress the expression of miR-29s. At mRNA level, some of these transcription factors, c-Myc and EZH2, were significantly activated in response to HF diet. The present results indicated that the LPL expression could be activated by high fat diet in multiple tissues and the induction of LPL is post-transcriptionally regulated by miR-29a/b. Furthermore, the transcription of miR-29 in mice adipose was regulated by certain transcriptional factors. Overall, LPL mRNA altered in multiple tissues in response to high fat diet and is potentially regulated through transcription factors and microRNAs
