RESUMO
Adipose tissue dysfunction plays an important role in metabolic diseases associated with chronic inflammation, insulin resistance and lipid ectopic deposition in obese patients. In recent years, it has been found that under the stimulation of adipocyte endoplasmic reticulum stress (ERS), the over-activated ER unfolded protein response (UPR) exacerbates the inflammatory response of adipose tissue by interfering with the normal metabolism of adipose tissue, promotes the secretion of adipokines, and affects the browning and thermogenic pathways of adipose tissue, ultimately leading to the manifestation of metabolic syndrome such as ectopic lipid deposition and disorders of glucolipid metabolism in obese patients. This paper mainly summarizes the relationship between adipocyte ERS and obese adipose tissue dysfunction and provides an overview of the mechanisms by which ERS induces metabolic disorders such as catabolism, thermogenesis and inflammation in obese adipose tissue through the regulation of molecules and pathways such as NF-κB, ADPN, STAMP2, LPIN1, TRIP-Br2, NF-Y and SIRT2 and briefly describes the current mechanisms targeting adipocyte endoplasmic reticulum stress to improve obesity and provide ideas for intervention and treatment of obese adipose tissue dysfunction.
RESUMO
Objective: Clinical data has recently shown an association between Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and zonisamide. The purpose of this study was to thoroughly evaluate the efficacy and safety of zonisamide in PD and DLB. Methods: Pubmed, the Cochrane Library, Web of Science, and Embase databases were searched for all randomized clinical trials (RCTS) on the role of zonisamide in PD and DLB that were completed by April 18, 2022. UPDRS II (off) total score, UPDRS III total score, Daily "off" time, and UPDRS Part IV, Nos. 32, 33, and 34 were used as clinical efficacy endpoints. Adverse events reported in the RCTs will be considered in the final safety analysis. To better understand the effect of zonisamide on the efficacy and safety of PD and DLB, the UPDRS III total score and the six overlapping adverse events were examined in subgroups. Either a fixed effects model analysis (OR) or a random effects model analysis (MD) is used to figure out the mean difference (MD) and the relative risk. Results: Seven articles involving 1749 patients (916 PD and 833 DLB) were included in this study. Compared to the control group, zonisamide could significantly reduce the UPDRS III total score in patients with PD and DLB (WMD-2.27 [95% CI: -3.06, -1.48], p < 0.0001). For patients with PD, compared to the control group, zonisamide could significantly reduce the UPDRS II (off) total score (WMD-0.81 [95% CI: -1.36, -0.26], p = 0.004), daily "off" time (WMD-0.67 [95% CI: -1.10, 0.24], p = 0.002), and UPDRS part IV, No. 32 worsen (OR-3.48 [95% CI: 1.20, 10.10], p = 0.02). In terms of safety, compared with the control group, for patients with DLB, zonisamide could significantly increase the incidence of contusion (OR-0.60 [95% CI: 0.38, 0.96], p = 0.03) and may increase the probability of reduced appetite (OR-3.13 [95% CI: 1.61, 6.08], p = 0.0008). And for patients with PD, zonisamide may increase the probability of somnolence (OR-2.17 [95% CI: 1.25, 3.76], p = 0.006). Conclusions: For the analysis of the current study results, our results show that zonisamide could improve the motor function in patients with PD and DLB and improve the activities of daily living (off) and wearing off and decrease the duration of dyskinesia in patients with PD. In terms of safety, the use of zonisamide significantly increases the probability of contusion in patients with DLB and may increase the probability of reduced appetite in patients with DLB and somnolence in patients with PD. Zonisamide appears to be a new treatment option for patients with PD and DLB. However, the effectiveness and safety of zonisamide in the treatment of PD and DLB need to be further investigated.
