Novel Mechanisms Modulating Palmitate-Induced Inflammatory Factors in Hypertrophied 3T3-L1 Adipocytes by AMPK

Abstract

Objective A growing body of evidence indicates that AMP-activated protein kinase (AMPK) contributes to not only energy metabolic homeostasis but also the inhibition of inflammatory responses. However, the underlying mechanisms remain unclear. To elucidate the role of AMPK, in this study, we observed the effects of AMPK activation on monocyte chemoattractant protein-1 (MCP-1) release in mature 3T3-L1 adipocytes. Methods We observed signal transduction pathways regulating MCP-1, which increased in obese adipocytes, in an in vitro model of hypertrophied 3T3-L1 adipocytes preloaded with palmitate. Results Palmitate-preloaded cells exhibited significant increase in MCP-1 release and triglyceride (TG) deposition. Increased MCP-1 release and TG deposition were significantly decreased by an AMPK activator. In addition, the AMPK activator not only markedly diminished MCP-1 secretion but also augmented phosphorylation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK) 1/2. In contrast, MCP-1 release suppression was abolished by the AMPK inhibitor compound C and the MEK inhibitor U0126. Conclusions MCP-1 release from hypertrophied adipocytes is suppressed by AMPK activation through the NF-κB and ERK pathways. These findings provide evidence that AMPK plays a crucial role in ameliorating obesity-induced inflammation.

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

“…In contrast, supplementation of catechin markedly increased the level of p-AMPK, p-SIRT1, p-FOXO3a and p-NF-κB, and gradually closed to the control group. Similar effects were observed for the extracts from grape [6], black tea [22], brown alga [34]. Consistent with our findings, a few studies have also demonstrated that synergistic activation of AMPK and SIRT1 can promote the expression of anti-inflammatory cytokines, and prevent the expression of pro-inflammatory cytokines via NF-κB signaling pathway in LPS-induced cells [35, 36].…”

“…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].…”

Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin

“…MCP1 is an adipocytokine that is crucial for triggering macrophage infiltration into adipose tissue and recruiting more macrophages to sites of infiltration, where these activated macrophages further stimulate MCP1 production. In a model of hypertrophied adipocytes, MCP1 protein was shown to be significantly inhibited by treatment with metformin by a mechanism involving the NFκB pathway [ 44 ]. As a whole, these previous results are in line with our present findings, and together they confirm a role for metformin in ameliorating systemic inflammation, with a specific action in adipose tissue, where it reduces expression of MCP1 and NFκB.…”

“…In fact, when compared with obese subjects without metabolic complications, our obese diabetic patients treated with metformin exhibited a significantly lower expression of the inflammasome components NRLP3 and ASC and a drop in the systemic release of IL1β and IL18, the specific cytokines resulting from NLRP3 inflammasome activation. This response could have been mediated by the well-known effect of metformin on NFκB and ROS decline [ 44 , 46 ]. In line with this, Li et al reported that metformin prevented NLRP3 inflammasome activation by suppressing endoplasmic reticulum (ER) stress, indicated by dephosphorylation of IRE1α and eIF2α in the adipose tissue of diabetic mice [ 19 ].…”

Efeito protetor do baço contra a resposta inflamatória do tecido adiposo perivascular do leito mesentérico de camundongos obesos.

“…Além de seu papel regulatório no metabolismo, a AMPK inibe a resposta inflamatória. Nos adipócitos, a AMPK reduz a secreção de IL-6, IL-8 e MCP-1 (LIHN et al, 2008, MORITA et al, 2018. Camundongos obesos deficientes de AMPKβ1 apresentam aumento das adipocinas pró-inflamatórias TNF-α, MCP-1 e leptina no sangue periférico e aumento de TNF- e IL-1 no tecido adiposo periepididimal (GALIC et al, 2011).…”