ABSTRACT
Recent work suggests that Formoterol could be involved in the metabolic regulation of adipose tissue. It's unknown whether Formoterol possesses an effect against adipogenesis. Here, we found that Formoterol prevented adipocyte differentiation by reducing lipid accumulation, evidenced by reduced Oil Red O staining, declined intracellular triglyceride level, and downregulation of adipogenic factors (PPAR-γ, C/EBPα, and Glut4) in differentiation medium (MDI) stimulated 3T3-L1 preadipocytes. The administration of Formoterol ameliorated obesity in high fat diet (HFD) fed mice, which was evidenced by decreased body weight and ratio of fat/body weight, reduced adipocyte size, and decreased visceral adipocyte tissue weight. Furthermore, the expression level of adipogenic factors in white adipocyte tissues of HFD-fed mice was greatly repressed by Formoterol. Lastly, thermogenic markers (p-AMPK/AMPK, PGC-1α, and UCP-1) were dramatically upregulated by Formoterol. Collectively, Formoterol prevented adipogenesis and obesity in obese mice by regulating the PPARγ/C/EBPα axis and the AMPK/PGC-1α pathway.
ABSTRACT
BACKGROUND AND PURPOSE: Excessive lipid accumulation in adipose tissues and deregulation of adipogenesis-induced obesity affect millions of people worldwide. Feprazone, a nonsteroidal anti-inflammatory drug, has a wide clinical use. However, it is unknown whether Feprazone possesses an antiadipogenic ability. The aim of this study is to investigate whether Feprazone possesses an antiadipogenic ability in 3 T3-L1 cells and an antiobesity capacity in mouse models. METHODS: An MTT assay was used to determine the optimized incubation concentrations of Feprazone in 3 T3-L1 cells. The lipid accumulation was evaluated using Oil Red O staining. The concentrations of triglyceride and glycerol release were detected to check the lipolysis during 3 T3-L1 adipogenesis. A quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of sterol regulatory element-binding protein-1C (SREBP-1C) and fatty acid binding protein 4 (FABP4) in treated cells. The expressions of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein α (C/EBP-α), adipose triglyceride lipase (ATGL), and aquaporin-7 (AQP-7) were detected using qRT-PCR and Western blot analysis. After the high-fat diet (HFD) mice were treated with Feprazone, the pathological state of adipocyte tissues was evaluated using HE staining. The adipocyte size, visceral adipocyte tissue weight, and bodyweights were recorded. RESULTS: According to the proliferation result, 30 and 60 µM Feprazone were used as the optimized concentrations of Feprazone. In the in vitro study, lipid accumulation, elevated production of triglycerides, the release of glycerol, upregulated SREBP-1C, FABP4, PPAR-γ, and C/EBP-α and downregulated ATGL and AQP-7 in the 3 T3-L1 adipocytes induced by the adipocyte differentiation cocktail medium were significantly reversed by treatment with Feprazone. In the in vivo experiment, we found that the increased adipocyte size, visceral adipocyte tissue weight, and body weights induced by HFD feeding in mice were significantly suppressed by the administration of Feprazone. CONCLUSION: Feprazone might display anti-adipogenic and antiobesity capacities in in vitro 3 T3-L1 cells and in vivo mice.
ABSTRACT
Objective: Elevated expression of Yes-associated protein (YAP1) involves in the pathogenesis of cervical cancer. Bioinformatics analysis showed a targeting relationship between miR-205 and the 3'-UTR of YAP1. In this study, we aim to explore the role of miR-205 in the proliferation, apoptosis, or cisplatin (CDDP) resistance of cervical cancer cells. Patients and Methods: The dual luciferase reporter gene assay verified the relationship between miR-205 and YAP1. The CDDP-resistant cell line Hela/CDDP cells were cultured in vitro and divided into miR-NC group, miR-205 mimic group, and miR-205 inhibitor group followed by analysis of the expression of miR-205 and YAP1 mRNA by quantitative real-time polymerase chain reaction (qRT-PCR), and YAP1 protein level by western blot. Results: There was a targeted relationship between miR-205 and YAP1 mRNA. Compared with cervical cell line HCerEpiC cells, miR-205 expression was significantly decreased and YAP1 mRNA and protein expression was significantly increased in Hela cells (p < 0.01). Compared with miR-NC group, YAP1 protein expression in HeLa/CDDP cells was significantly decreased, cell apoptosis was increased, and proliferation was inhibited in miR-205 mimic-transfected Hela/CDDP cells (p < 0.01). Opposite results were obtained in miR-205 inhibitor-transfected Hela/CDDP cells. Conclusions: The expression of miR-205 is related to the CDDP resistance of cervical cancer cells. Increasing the expression of miR-205 can downregulate the expression of YAP1, inhibit the proliferation and promote apoptosis of cervical cancer cells, and enhance the sensitivity to CDDP.
