FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity

Xiong, Xiao-Qing; Geng, Zhi; Zhou, Bing; Zhang, Feng; Han, Ying; Zhou, Ye-Bo; Wang, Juejin; Gao, Xing-Ya; Chen, Qi; Li, Yuehua; Kang, Yu-Ming; Zhu, Guo‐Qing

doi:10.1016/j.metabol.2018.01.013

Cited by 127 publications

(75 citation statements)

References 45 publications

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“…During this process, M1-polarized macrophages secreted proinflammatory cytokines and impaired insulin action. On the contrary, M2-polarized macrophages secreted anti-inflammatory cytokines and later contributed to the maintenance of insulin sensitivity (9,39,40). Coincident with previous data (41), our results showed increased obesity-induced inflammation, M1-type polarization of macrophages, and compromised insulin activities in WT mice exposed to an HFD for 12 weeks.…”

Section: Discussionsupporting

confidence: 90%

Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

Yang

Lou

et al. 2020

Obesity

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Objective The aim of this study was to investigate the effect of Von Willebrand factor (VWF) on high‐fat diet (HFD)‐induced hepatic steatosis, insulin resistance, and inflammation in mice. Methods The expression of VWF was detected in obese mice. Wild‐type and VWF knockout mice were fed a normal chow diet or an HFD, and then biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations. Inflammatory cytokine levels and the number of hepatic macrophages were determined in these mice fed an HFD. Results VWF expression was significantly increased in obese mice. VWF−/− mice were less obese and had improved hepatic steatosis, balance of lipid metabolism, and insulin resistance in response to HFD. Furthermore, VWF deficiency attenuated HFD‐induced systemic and hepatic inflammation. In addition, VWF deficiency rescued the abnormal accumulation of hepatic macrophages. Conclusions These data demonstrated VWF deficiency improves hepatic steatosis, insulin resistance, and inflammation. Furthermore, the protective effects are mediated via regulation of hepatic macrophages.

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Section: Discussionsupporting

confidence: 90%

Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

Yang

Lou

et al. 2020

Obesity

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“…The improvement effects of Fndc5 are significantly alleviated by the AMPK inhibitor Compound C (CC), but did not change by utilizing an AMPK activator, AICAR. These data demonstrate that AMPK reduces inflammation and M1 macrophage polarization by Fndc5 [52] ( Table 1). This function of irisin, compared with those described already for irisin through MAPK signaling, demonstrated that irisin exerts its effects through alternative pathways.…”

Section: Fndc5 Attenuates Inflammation and Insulin Resistance Via Ampmentioning

confidence: 55%

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

et al. 2020

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Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.

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“…Activation of pyruvate kinase isozymes M2 enhanced IL-10 secretion in LPS-stimulated BMDM, favouring an M2 phenotype and reduced M1 polarisation [ 65 ]. Macrophage M1 polarisation was reduced through AMPK activation by fibronectin type III domain-containing 5 (FNDC5), and worsened when FNDC5 was inhibited, thus lowering AMPK levels in the adipose tissue of HFD-fed mice [ 76 ]. Palmitate-treated macrophages treated with AICAR was able to reduce the number of M1 macrophages while subsequently increasing the M2 macrophage population [ 32 ].…”

Section: Modulation Of Ampk Activation By Nutrientsmentioning

confidence: 99%

Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

Lyons

Roche

2018

IJMS

122

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Nutritional status provides metabolic substrates to activate AMP-Activated Protein Kinase (AMPK), the energy sensor that regulates metabolism. Recent evidence has demonstrated that AMPK has wider functions with respect to regulating immune cell metabolism and function. One such example is the regulatory role that AMPK has on NLRP3-inlflammasome and IL-1β biology. This in turn can result in subsequent negative downstream effects on glucose, lipid and insulin metabolism. Nutrient stress in the form of obesity can impact AMPK and whole-body metabolism, leading to complications such as type 2 diabetes and cancer risk. There is a lack of data regarding the nature and extent that nutrient status has on AMPK and metabolic-inflammation. However, emerging work elucidates to a direct role of individual nutrients on AMPK and metabolic-inflammation, as a possible means of modulating AMPK activity. The posit being to use such nutritional agents to re-configure metabolic-inflammation towards more oxidative phosphorylation and promote the resolution of inflammation. The complex paradigm will be discussed within the context of if/how dietary components, nutrients including fatty acids and non-nutrient food components, such as resveratrol, berberine, curcumin and the flavonoid genistein, modulate AMPK dependent processes relating to inflammation and metabolism.

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FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity

Cited by 127 publications

References 45 publications

Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

Von Willebrand Factor Deficiency Improves Hepatic Steatosis, Insulin Resistance, and Inflammation in Mice Fed High‐Fat Diet

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

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