Research Article: Catechin attenuates TNF-α induced inflammatory response via AMPK-SIRT1 pathway in 3T3-L1 adipocytes

Date Published: May 17, 2019

Publisher: Public Library of Science

Author(s): An-Wei Cheng, Xin Tan, Jin-Yue Sun, Chun-Mei Gu, Chao Liu, Xu Guo, Partha Mukhopadhyay.

http://doi.org/10.1371/journal.pone.0217090

Abstract

Chronic inflammation is a fundamental symptom of many diseases. Catechin possesses anti-oxidant and anti-inflammatory properties. However, the mechanism of catechin to prevent inflammation in 3T3-L1 adipocytes caused by TNF-α remains unknown. Therefore, the effects of catechin on the gene expression of cytokines and the activation of cell signals in TNF-α induced 3T3-L1 adipocytes were investigated. The effects of catechin on adipogenesis and cell viability were detected by Oil Red O staining and CCK-8 assay, respectively. The genes expression of cytokines was determined by real-time RT-PCR. The expression of NF-κB, AMPK, FOXO3a and SIRT1 on translation level was determined by western blotting analysis. The results demonstrated that catechin significantly enhanced adipogenesis and cell viability. catechin inhibited the gene expression of pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-12p35, and inflammatory enzymes including iNOS and COX-2, but enhanced the gene expression of anti-inflammatory cytokines including IL-4 and IL-10. Catechin also inhibited the activation of NF-κB, AMPK, FOXO3a and SIRT1, but increased the phosphorylation level of the above factors. All these results indicated that as a potential therapeutic strategy catechin has the ability of attenuating inflammatory response triggered by TNF-α through signaling cascades involved in inflammation and cytokines.

Partial Text

Inflammation is a vital survival mechanism in human but it would be dangerous when it loses balance in metabolism and survives, and may slowly develop into a chronic state. Several metabolic disorders, such as obesity, diabetes and atherosclerosis, stir up immune defense mechanisms and stimulate chronic inflammation which in turn aggravate the symptoms of the diseases [1–3]. Especially in recent years obesity has become a worldwide health problem. Obesity can lead to inflammation, and its induced insulin resistance is the key to the occurrence of metabolic syndrome. Some studies have shown that adipose tissue/cells are not only the place for energy storage, but also secrete a variety of adipokines and inflammatory factors [4], and there is a certain relationship between energy metabolism and immune regulation at the cellular level. The formation of inflammatory mediators is a highly energy-consuming process, and the energy metabolism state of cells is closely related to the occurrence and development of inflammation. The inflammatory effects of tumor necrosis factor (TNF)-α are triggered by the activation of the inflammatory signaling networks, including nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), forkhead box O3a (FOXO3a), sirtuin1 (SIRT1) pathways in key metabolic tissues as well as adipocytes [5–9], which is responsible for the increasing of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-12, and inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), but for the decreasing of anti-inflammatory cytokines, such as IL-4 and IL-10 [6,7,10–13].

Inflammation, especially chronic inflammation, is an important defense response to resist pathogen invasion and repair tissue damage. Chronic inflammation and cellular senescence are inseparable in the process of accelerated or premature aging [28]. This is due to the associated production of pro-inflammatory cytokines (such as IL-1, IL-6, IL-12), anti-inflammatory cytokines (such as IL-4, IL-10) and inflammatory enzymes (such as iNOS, COX-2). These cytokines and enzymes drive the regeneration and activation of immune cells that achieve a balance between inflammatory and metabolic functions [29]. Natural products can provide abundant resources for anti-inflammatory compounds. Some dietary polyphenols, such as resveratrol, catechin, and quercetin, have been shown to be effective in preventing or alleviating inflammatory [22, 30]. The current work demonstrated that catechin had a capacity to protect adipocytes from TNF-α deleterious, with the increasing of the cell adipogenesis and viability. Catechin in the range of 10–100 μg/mL inhibited TNF-α induced the expression of genes involved in pro-inflammatory cytokines (IL-1, IL-6, IL-12) and inflammatory enzymes (iNOS, COX-2), and promoted TNF-α induced the expression of genes involved in anti-inflammatory cytokines (IL-4, IL-10). IL-4 and IL-10 are the protective cytokines against TNF-α induced inflammation. Vazquezprietoet al. [25] showed that TNF-α dependent transcription of pro-inflammatory genes (IL-6, resistin) was inhibited by (-)-epicatechin, which was consistent with our results. Similar result was also detected in the report from Chia et al. [6].

 

Source:

http://doi.org/10.1371/journal.pone.0217090

 

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