Comparative studies on the effects of high-fat diet, endurance training and obesity on Ucp1 expression in male C57BL/6 mice.

BACKGROUND: Obesity triggers a variety of severe conditions, therefore deteriorates metabolism rate of adipose tissues and muscles. Uncoupling proteins which are highly stimulated by fatty acids are potential targets for anti-obesity agents through breaking the electron gradient in the mitochondrial matrix and creating imbalances in the electron transport chain, thereby increasing the amount of substrate used to produce energy. Therefore, the aim of present study is assessment of exercise and high fat diet on expression level of Ucp1 subcutaneous white and brown adipose tissues (scWAT & BAT) respectively. METHODS: To perform experiments, 48 male C57BL/6 mice were divided to two major groups and fed with high fat diet (HFD) or low fat diet (LFD) during a period of 12 weeks. After the first intervention, each groups was divided into four groups randomly as (HF-EX), (HF-SED), (LF-EX), (LF-SED) [EX: exercise; SED: sedentary] in form of treadmill running for 45 min/day, 5 days/week during 8 weeks. One day after the last practice session, mice were sacrificed and Ucp1 expression was assessed on scWAT & BAT. RESULTS: Data indicated a down-regulation in scWAT Ucp1 in obese mice similar to what observed for the expression of Pgc1α. Both, BAT Ucp1 and Pgc1α mRNA decreased significantly in response to obesity and physical activity. Moreover, exercise caused significant decrease in scWAT mitochondrial proteins contradictory to BAT. CONCLUSION: Taken together, exercise exerted controversial effects compared with HFD and obesity on expression of Ucp1 and Pgc1α in scWAT dissimilar to BAT tissues, concluding that obesity may cause a resistance to exercise in terms of metabolic demands for scWAT tissue.

MiR-9-5p and miR-106a-5p dysregulated in CD4+ T-cells of multiple sclerosis patients and targeted essential factors of T helper17/regulatory T-cells differentiation.

OBJECTIVES: Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients. MATERIALS AND METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor γt (RORγt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools. RESULTS: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 were up-regulated in relapsing and remitting phases of MS, respectively. CONCLUSION: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis.