Uncoupling Proteins (ucps) And Obesity, The Relationship Between Research And Ucp4 Gene Function In Fat Cells Discussion

Obesity, one of the common metabolic diseases, can be theimportant risk factor for many severe diseases, such as diabetes,hypertension, cardiovascular diseases and stroke. According to epidemicsresearch, the prevalence of obesity has been significantly increasing andhas grown to be a global epidemic disease in recent decade. Especiallycurrently, an epidemic of obesity also has been observed in children andadolescents across the developed and developing world. Totally, pediatricobesity has become a very important problem and must be resolvedimmediately.It has been widely accepted that inherit acts as a key role in thedevelopment of obesity. According to the last version of the Gene Map ofObesity, over 200 genes and genomic regions have been found to berelated to obesity. Uncoupling proteins (UCPs), one family of aniontransporters presenting in the mitochondrial inner membrane, have beenattracted considerable interest in obesity research, because of their certainroles in energy metabolism. In mammals, UCPs include five subtypes.Many scientists have study the relationship between obesity and UCP1,UCP2, UCP3. However, few reports put the focus on UCP4 and UCP5. Inthis research, we explored the expression characters of UCPs in obesityand the role of UCP4 in adipocytes. To reveal the multi-tissue expression characters of UCPs in obesity,we assayed their different mRNA expression in obese rodent usingRT-PCR. Diet-induced obese (DIO) SD rats and genetic ob/ob mice wereprepared, and the expression of UCPs in white adipose tissue, brownadipose tissue, brain, muscle and liver were examined respectively. Thedata showed that expression of UCPs in white adipose tissue, brownadipose tissue, brain, muscle and liver changed in obese rodents. Besidesexpressing in brain, UCP4 gene expressed in white adipose tissue, muscleand liver. In DIO rats, the UCP4 mRNA level down-regulated notably inomental adipose tissue, brain, muscle and liver. While in ob/ob mice,except for down-regulate significantly in brain, UCP4 expression had notany change in other tissues.Furthermore, we choose 3T3-L1 as our study model and investigatedthe function of UCP4 in adipocytes. After being induced to differentiateinto mature by MDI, 3T3-L1 overexpressing UCP4 showed significantlyattenuated differentiation of preadipocytes into adipocytes. Compared tocontrol cells transfected with empty vectors, the lipid droplets in 3T3-L1overexpressing UCP4 appeared later and were smaller. RT-PCR analysisfor the expression of C/EBPα, PPARγ2, LPL, AP2 and FAS during3T3-L1 differentiation indicated that the expression of these adipocytesmarker genes were down-regulated in 3T3-L1 transfected with UCP4.It is well known that 95% 3T3-L1 differentiate into mature adipoctes at the 8th day during differentiation. To clarify the effect of UCP4 on lipidaccumulation, we collected the adipocytes at the 8th day duringdifferentiation and measured the cellular total triglycerides. The level ofcellular triglycerides was also significantly lower in cells overexpressingUCP4. The results suggested that UCP4 could inhibit the process of lipidaccumulation in adipocytes.Cell proliferation was explored by MTT assay, and cell cycles wereanalyzed by flow cytometry. We observed that 3T3-L1 overexpressingUCP4 grew faster and more of them stayed in S phase compared tocontrol cells. The results suggested that UCP4 could promote cellmultiplication and modulate cell cycles.Cells were induced to apoptosis by serum deprivation andsubsequently evaluated for apoptosis rate with Annexin-V assays. Thedata demonstrated that UCP4 overexpression protected preadipocytesfrom apoptosis.In addition, 2-Deoxy-glucose labeled by isotope ~3H was used toassay glucose uptake of mature adipocytes. The data showed that ectopicexpression of UCP4 dramatically decreases both basal glucose uptake andinsulin-stimulated glucose uptake in adipocytes. Simultaneously, RT-PCRanalysis for the expression of GLUT1 and GLUT4 indicated that theexpression of glucose transporters were both downregulated.In summary, we described the multi-tissue expression characters of UCPs in obesity rodents and explored the expression and function ofUCP4 in adipose tissue. These results supply more proof of study onrelationship between UCP4 and obesity.