Objective: Many studies have highlighted the relation of mitochondrial dysfunction with obesity as both of contributors and consequences. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have evolved, including mitochondrial unfolded protein response (UPRmt). The UPRmt senses the proteostatic disturbances specifically in the mitochondria and resolves the stress by retrograde signaling to the nucleus and consequent transcriptional activation of protective genes. In this study, we investigated the UPRmt related with obesity in the human visceral adipose tissue.
Methods: We obtained omental adipose tissue from 48 females with normal glucose tolerance undergoing gynecologic surgery. We examined the mRNA expression of OXPHOS complex, PPARGC1A, and UPRmt-related genes in the visceral adipose tissue using quantitative RT-PCR, and performed correlation analysis of this expression with the clinical characteristics of the subjects. We also measured mtDNA content and malondialdehyde level, a naturally occurring product of lipid peroxidation, in the visceral adipose tissue.
Results: The mean age of study subjects was 42.5 ± 5.8 years old and mean BMI was 23.4 ± 3.5 kg/m2. The LONP1 mRNA expression was only positively correlated with body mass index (BMI) (ρ = 0.308, p = 0.050) among UPRmt-related genes. The LONP1 mRNA expression was also positively correlated with the mRNA expression of mitochondrial chaperones, HSPD1 and DNAJA3 (ρ=0.622, p<0.001; ρ=0.409, p=0.012, respectively), but not with the mRNA expression of OXHPOS complexes and PPARGC1A, mtDNA content and malondialdehyde level in the visceral adipose tissue. In the western blot, the LONP1 expression was increased in the adipose tissue of patients with highest BMI compared with the adipose tissue of patients with lowest BMI.
Conclusion: The LONP1 was increased in the visceral adipose tissue of obese human. The clinical implication of the increased LONP1 expression in the obesity needs to be clarified by further studies.