Browning effect of LncRNA00602 in Ad36-induced differentiated adipocytes.

Long noncoding RNAs (LncRNAs) play critical roles in regulating gene expression and cellular processes, including adipocyte differentiation. LncRNA00602 is upregulated in adipose tissue. Therefore, we aimed to investigate the potential role of LncRNA00602 in adenovirus type 36 (Ad36)-induced adipocyte browning. Human adipose-derived stem cells were induced into adipocytes by Ad36, and were divided into the control and LncRNA00602 knockdown groups. Lipid droplets and mitochondria were stained with BODIPY and Mito Tracker Red, respectively. The binding of LncRNA00602 to upstream frameshift 1 (UPF1) was detected by RNA-immunoprecipitation. We used silver staining, co-immunoprecipitation, and mass spectrometry to detect and identify the protein complexes bound to UPF1. The control and caveolin-1 (CAV-1) knockdown groups were set up. The mRNA and protein levels were detected by real-time quantitative PCR and Western Blot. On days 2 and 4, compared with the control group, the lipid droplet area of adipocytes in the LncRNA00602 knockdown group was larger, whereas the mitochondrial fluorescence intensity was lower. We observed significant reductions in the mRNA and protein expression levels of ATP5O and COX5B in the LncRNA00602 knockdown group. LncRNA00602 could bind to UPF1. The proteins bound to UPF1 were involved in the nonsense-mediated mRNA decay pathway and lipid metabolism. Additionally, we found that CAV-1 mRNA and protein in the LncRNA00602 knockdown group were significantly lower than those in the control group. Furthermore, the mRNA and protein expression levels of UCP1, ATP5O, and COX5B in the CAV-1 knockdown group were significantly lower than those in the control group. In adipocytes induced by Ad36, LncRNA00602 may upregulate the expression of UCP1 and mitochondrial oxidative phosphorylation-related enzyme genes via the complex composed of UPF1 and CAV-1, thus inducing the browning of adipocytes.