Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress.

Obesity is a strong predictor of heart disease, insulin resistance, and type II diabetes. Chronic, low-grade inflammation links obesity and insulin resistance through mitogen-activated protein kinase (MAPK) signaling pathways. Upstream kinases activate MAPK signaling, while MAPK-specific dual-specificity phosphatases (DUSPs) act as key modulators and controllers of MAPK deactivation (i.

Curcumin Inhibits 3T3-L1 Preadipocyte Proliferation by Mechanisms Involving Post-transcriptional p27 Regulation.

Previous reports from our lab have shown that Skp2 is necessary for p27 degradation and cell cycle progression during adipocyte differentiation. Data presented here demonstrate that the anti-inflammatory, anti-obesity phytochemical curcumin blocked Skp2 protein accumulation during early adipocyte hyperplasia. In addition, curcumin dose-dependently induced p27 protein accumulation and G1 arrest of synchronously replicating 3T3-L1 preadipocytes.

Modulation of IL-27 in adipocytes during inflammatory stress.

Objective: While it is well established that adipose tissue-derived inflammation plays an important role in the pathogenic mechanisms linking obesity with metabolic dysfunction, the inflammatory mediators involved have not been fully elucidated. Here, we explored IL-12 family cytokines with a focus on IL-27 during obesity-induced inflammation in mice and cultured adipocytes (ADs) following exposure to inflammatory stimuli.

Methods: Relative mRNA abundance of IL-12 cytokines was assessed by reverse transcription polymerase chain reaction (RT-PCR) in genetically obese B6-ob/ob mice as well as C57BL/6J mice fed a high-fat diet and in ADs following exposure to inflammatory stimuli.

Mitogen-Dependent Regulation of DUSP1 Governs ERK and p38 Signaling During Early 3T3-L1 Adipocyte Differentiation.

Knowledge concerning mechanisms that control proliferation and differentiation of preadipocytes is essential to our understanding of adipocyte hyperplasia and the development of obesity. Evidence has shown that temporal regulation of mitogen-activated protein kinase (MAPK) phosphorylation and dephosphorylation is critical for coupling extracellular stimuli to cellular growth and differentiation. Using differentiating 3T3-L1 preadipocytes as a model of adipocyte hyperplasia, we examined a role for dual-specificity phosphatase 1 (DUSP1) on the timely modulation of MAPK signaling during states of growth arrest, proliferation, and differentiation.

Impact of obesity on IL-12 family gene expression in insulin responsive tissues.

Mounting evidence has established a role for chronic inflammation in the development of obesity-induced insulin resistance, as genetic ablation of pro-inflammatory cytokines and chemokines elevated in obesity improves insulin signaling in vitro and in vivo. Recent evidence further highlights interleukin (IL)-12 family cytokines as prospective inflammatory mediators linking obesity to insulin resistance. In this study, we present empirical evidence demonstrating that IL-12 family related genes are expressed and regulated in insulin-responsive tissues under conditions of obesity.

Impact of reference gene selection for target gene normalization on experimental outcome using real-time qRT-PCR in adipocytes.

Background: With the current rise in obesity-related morbidities, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) has become a widely used method for assessment of genes expressed and regulated by adipocytes. In order to measure accurate changes in relative gene expression and monitor intersample variability, normalization to endogenous control genes that do not change in relative expression is commonly used with qRT-PCR determinations. However, historical evidence has clearly demonstrated that the expression profiles of traditional control genes (e.