1,3,6,7‐Tetrahydroxy‐8‐prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages

Li, Dan; Liu, Qianyu; Sun, Wenyue; Chen, Xiuping; Wang, Ying; Sun, Yuxiang; Lin, Ligen

doi:10.1111/bph.14162

Cited by 45 publications

(35 citation statements)

References 62 publications

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“…Cell viability was determined by MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay as described previously . C2C12 cells were seeded in 96‐well plates at a density of 1 × 10 4 cells per well.…”

Section: Methodsmentioning

confidence: 99%

“…To examine the acetylated levels of PGC-1α and FoxO3a, the immunoprecipitation (IP)/western blot analyses were performed as described previously. 29,33 The detailed procedure was described as follows: protein A/G agarose beads were washed with RIPA lysis buffer thrice prior to IP. Primary antibody was incubated with protein A/G agarose beads at 4°C for 1 h with gently mixing.…”

Section: Immunoprecipitationmentioning

confidence: 99%

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Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

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Background Muscle atrophy and weakness are adverse effects of high dose or the sustained usage of glucocorticoids. Loss of mitochondria and degradation of protein are highly correlated with muscle dysfunction. The deacetylase sirtuin 1 (SIRT1) plays a vital role in muscle remodelling. The current study was designed to identify myricanol as a SIRT1 activator, which could protect skeletal muscle against dexamethasone‐induced wasting. Methods The dexamethasone‐induced atrophy in C2C12 myotubes was evaluated by expression of myosin heavy chain, muscle atrophy F‐box (atrogin‐1), and muscle ring finger 1 (MuRF1), using western blots. The mitochondrial content and oxygen consumption were assessed by MitoTracker staining and extracellular flux analysis, respectively. Muscle dysfunction was established in male C57BL/6 mice (8–10 weeks old, n = 6) treated with a relatively high dose of dexamethasone (25 mg/kg body weight, i.p., 10 days). Body weight, grip strength, forced swimming capacity, muscle weight, and muscle histology were assessed. The expression of proteolysis‐related, autophagy‐related, apoptosis‐related, and mitochondria‐related proteins was analysed by western blots or immunoprecipitation. Results Myricanol (10 μM) was found to rescue dexamethasone‐induced muscle atrophy and dysfunction in C2C12 myotubes, indicated by increased expression of myosin heavy chain (0.33 ± 0.14 vs. 0.89 ± 0.21, * P < 0.05), decreased expression of atrogin‐1 (2.31 ± 0.67 vs. 1.53 ± 0.25, * P < 0.05) and MuRF1 (1.55 ± 0.08 vs. 0.99 ± 0.12, ** P < 0.01), and elevated ATP production (3.83 ± 0.46 vs. 5.84 ± 0.79 nM/mg protein, ** P < 0.01), mitochondrial content (68.12 ± 10.07% vs. 116.38 ± 5.12%, * P < 0.05), and mitochondrial oxygen consumption (166.59 ± 22.89 vs. 223.77 ± 22.59 pmol/min, ** P < 0.01). Myricanol directly binds and activates SIRT1, with binding energy of −5.87 kcal/mol. Through activating SIRT1 deacetylation, myricanol inhibits forkhead box O 3a transcriptional activity to reduce protein degradation, induces autophagy to enhance degraded protein clearance, and increases peroxisome proliferator‐activated receptor γ coactivator‐1α activity to promote mitochondrial biogenesis. In dexamethasone‐induced muscle wasting C57BL/6 mice, 5 mg/kg myricanol treatment reduces the loss of muscle mass; the percentages of quadriceps and gastrocnemius muscle in myricanol‐treated mice are 1.36 ± 0.02% and 0.87 ± 0.08%, respectively (cf. 1.18 ± 0.06% and 0.78 ± 0.05% in dexamethasone‐treated mice, respectively). Myricanol also rescues dexamethasone‐induced muscle weakness, indicated by improved grip strength (70.90 ± 4.59 vs. 120.58 ± 7.93 g, ** P < 0.01) and prolonged swimming exhaustive time (48.80 ± 11.43 vs. 83.75 ± 15.19 s, **...

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Section: Methodsmentioning

confidence: 99%

Section: Immunoprecipitationmentioning

confidence: 99%

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Shen

Liao

Liu

et al. 2019

J cachexia sarcopenia muscle

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“…The antibody‐based procedures used in this study comply with the recommendations made by the British Journal of Pharmacology (Alexander et al, ). Western blot analysis was performed as described previously (Li et al, ). In brief, protein concentration of each sample was quantified using the BCA protein assay kit.…”

Section: Methodsmentioning

confidence: 99%

Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

Shen

Liao

Zhang

et al. 2019

British J Pharmacology

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Background and Purpose Skeletal muscle is the predominant site for glucose disposal and fatty acid consumption. Emerging evidence indicates that the crosstalk between adipose tissue and skeletal muscle is critical in maintaining insulin sensitivity and lipid homeostasis. The current study was designed to investigate whether myricanol improves insulin sensitivity and alleviates adiposity through modulating skeletal muscle–adipose tissue crosstalk. Experimental Approach The therapeutic effect of myricanol was evaluated on palmitic acid (PA)‐treated C2C12 myotubes and high‐fat diet (HFD)‐fed mice. The crosstalk between myotubes and adipocytes was evaluated using Transwell assay. The cellular lipid content was examined by Nile red staining. The mitochondrial content was assessed by MitoTracker Green staining and citrate synthase activity, and the mitochondrial function was examined by Seahorse assay. Expression of mitochondria‐related and insulin signalling pathway proteins was analysed by Western blot, and the irisin level was determined by elisa kit. Key Results Myricanol increased mitochondrial quantity and function through activating AMP‐activated protein kinase, resulting in reduced lipid accumulation and enhanced insulin‐stimulated glucose uptake, in PA‐treated C2C12 myotubes. Furthermore, myricanol stimulated irisin production and secretion from myotubes to reduce lipid content in 3T3‐L1 adipocytes. In HFD‐fed mice, myricanol treatment alleviated adiposity and insulin resistance through enhancing lipid utilization and irisin production in skeletal muscle and inducing browning of inguinal fat. Conclusions and Implications Myricanol modulates skeletal muscle–adipose tissue crosstalk, to stimulate browning of adipose tissue and improve insulin sensitivity in skeletal muscle. Myricanol might be a potential candidate for treating insulin resistance and obesity.

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“…3T3-L1 preadipocytes were obtained from ATCC (Manassas, VA, USA) and maintained in DMEM containing 10% CS and 1% P/S. Cells were differentiated into adipocytes as reported previously [44]. Briefly, 2 days post-confluent 3T3-L1 preadipocytes were stimulated with DMEM supplemented with 10% FBS, 1 µM dexamethasone, 0.5 mM IBMX and 5 µg/mL insulin for 2 days.…”

Section: T3-l1 Cell Culture and Differentiationmentioning

confidence: 99%

SIRT3 Acts as a Positive Autophagy Regulator to Promote Lipid Mobilization in Adipocytes via Activating AMPK

Zhang

Liu

Tong

et al. 2020

IJMS

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Obesity is increasing at an alarming rate worldwide, which is characterized by the excessive accumulation of triglycerides in adipocytes. Emerging evidence has demonstrated that macroautophagy and chaperone-mediated autophagy (CMA) regulate lipid mobilization and play a key role in energy balance. Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase, which is important in regulating macroautophagy and lipid metabolism. It is still unknown whether SIRT3 modulates macroautophagy and CMA in adipocytes. The current study found that macroautophagy was dynamically regulated during 3T3-L1 adipocyte differentiation, which coincided with SIRT3 expression. In mature adipocytes, overexpression of SIRT3 activated macroautophagy, mainly on lipid droplets (LDs), through activating the AMP-activated protein kinase (AMPK)-unc-51-like kinase 1 (ULK1) pathway, which in turn resulting in smaller LD size and reduced lipid accumulation. Moreover, SIRT3 overexpression induced the formation of perilipin-1 (PLN1)-heat shock cognate 71 kDa protein (HSC70)-lysosome-associated membrane protein 2 (LAMP2) complex, to activate CMA and cause the instability of LDs in adipocytes. In summary, we found SIRT3 is a positive regulator of macroautophagy and CMA in adipocytes, which might be a promising therapeutic target for treatment of obesity and its related metabolic dysfunction.

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1,3,6,7‐Tetrahydroxy‐8‐prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages

Abstract: Taken together, our results indicate that TPX disrupts the inflammatory responses between macrophages and adipocytes, and attenuates adipose tissue inflammation.

Cited by 45 publications

References 62 publications

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Myricanol rescues dexamethasone‐induced muscle dysfunction via a sirtuin 1‐dependent mechanism

Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

SIRT3 Acts as a Positive Autophagy Regulator to Promote Lipid Mobilization in Adipocytes via Activating AMPK

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