Inflammation and ER stress differentially regulate STAMP2 expression and localization in adipocytes

Abstract

Background: Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress. Methods: 3T3-L1 and MEF adipocytes were treated with ER stress inducers thapsigargin and tunicamycin, and inflammation inducer TNFα. The treatments effect on STAMP2 expression and enzymatic function was assessed. In addition, 3T3-L1 adipocytes and HEK cells were utilized for Stamp2 promoter activity investigation performed with luciferase and ChIP assays. Results: ER stress significantly reduced both STAMP2 mRNA and protein expression in cultured adipocytes whereas TNFα had the opposite effect. Concomitant with loss of STAMP2 expression during ER stress, intracellular localization of STAMP2 was altered and total iron reductase activity was reduced. Stamp2 promoter analysis by reporter assays and chromatin immunoprecipitation, showed that induction of ER stress disrupts C/EBPαmediated STAMP2 expression. Conclusion: These data suggest a clear link between ER stress and quantitative and functional STAMP2-deficiency.

Developmental Origins of Metaflammation; A Bridge to the Future Between the DOHaD Theory and Evolutionary Biology

“…Based on these findings, we propose the involvement of ER stress programming in the developmental origins of 'Metaflammation' (Figure 2). This speculation is consistent with recent findings showing the critical involvement of ER stress in the co-regulation of chronic inflammation and metabolic disorders (43)(44)(45).…”

Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats

“…Our results and those of other groups have demonstrated that ER stress is a detrimental process when NP cells are subjected to stimuli, and repression of ER stress could mitigate IVDD (Lin et al, 2021;Luo et al, 2019;Wang et al, 2021). Thapsigargin (Tg), a classical inducer of ER stress in vitro, can increase cytoplasmic Ca 2+ levels by suppressing cells from pumping Ca 2+ back into the ER (Sikkeland et al, 2019;Zhang et al, 2014). In addition, Tg has been widely acknowledged as a commonly used activator of ER stress and ER stress-related changes in NP cells in ex vivo studies on IVDD (Krupkova et al, 2018;Novais et al, 2021;Yang et al, 2022;Zhang et al, 2022b).…”

4‐PBA inhibits hypoxia‐induced lipolysis in rat adipose tissue and lipid accumulation in the liver through regulating ER stress

“…Under normal conditions, ER in the adipocyte functions to meet the demands of protein synthesis and secretion, triglyceride synthesis, nascent lipid droplet formation, and nutrient sensing. However, ER function is overwhelmed and the UPR is activated under stressful conditions (Menikdiwela et al, 2019; Sikkeland et al, 2019). Therefore, perturbations in ER homeostasis exerts a vital pathogenic mechanism in multi metabolic disorders of adipose tissue (Khan & Wang, 2014; Suzuki et al, 2017).…”