Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle

Julien, Sylvain; Kim, Sun-Yee; Brunmeir, Reinhard; Sinnakannu, Joanna R.; Ge, Xiaojia; Li, Hongyu; Ma, Wei; Yaligar, Jadegoud; Kn, Bhanu Prakash; Velan, S. Sendhil; Röder, Pia V.; Zhang, Qiongyi; Sim, Choon Kiat; Wu, Jingyi; Garcia-Miralles, Marta; Pouladi, Mahmoud A.; Xie, Wei; McFarlane, Craig; Han, Weiping; Xu, Feng

doi:10.1371/journal.pbio.1002597

Cited by 39 publications

(38 citation statements)

References 63 publications

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“…or down-regulated the expression of GSK-3β in order to enhance Nrf2 entry [16]. Oxidative stress induced by high-fat diet is closely related to Nrf2-ARE pathway, in this study, the results showed that NaB signi cantly up-regulated PI3K and down-regulated GSK-3β expression, indicating that the mechanism NaB protects against oxidative stress may relate to the regulation of Nrf2-ARE signaling pathway.…”

Section: Discussionsupporting

confidence: 48%

Sodium butyrate protects against oxidative stress between obesity-prone and obesity-resistant rats induced by HFD through modulating Nrf2 pathway and mitochondrial function

Lu¹,

Sun²,

Li³

et al. 2020

Preprint

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Background Sodium butyrate (NaB) is obtained by fermenting dietary fiber via intestinal microflora and has recently been shown to improve some antioxidant enzymes in vivo. Methods In this study, we investigated the antioxidant effects of Sodium butyrate on obesity rats induced by high-fed diet. Results NaB intervention could effectively reduce the body weight of rats in the obesity-prone(OP) and obesity-resistant(OR)group, and reduce insulin resistance, plasma lipid, protect the gastrocnemius muscle and pancreas from oxidative stress induced by high fat diet, upregulate T-AOC, antioxidant enzyme activity and GSH/GSSG ratio, reduce ROS level and MDA content. NaB may increase Pi3k, Nrf2, Nqo-1, Ho-1 and inhibit Gsk-3β mRNA expression by regulating Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention could significantly increase the expression of Glut4 and Irs-1 mRNA in gastrocnemius muscle of OP and OR rats, suppress the expression of Bax and Caspase 3, increase the mRNA expression of Pdx1, MafA and Bcl-2, and increase insulin secretion and muscle insulin sensitivity. The regulatory effect of NaB was correlated with its significantly increased activity of mitochondrial antioxidant enzymes, mitochondrial membrane potential, NADH/NAD+ ratio, acetyl-CoA and ATP production, Tfam and Pgc-1α expression and mitochondrial DNA copy number. In addition, 6% NaB intervention in OP rats, 4%NaB intervention in OR rats were more significant, indicating that there were dose effects of NaB intervention in different obesity phenotypes. Conclusions NaB activates the Nrf2 antioxidant pathway, enhances the expression level of downstream antioxidant genes, improves the antioxidant capacity of obese rat tissues, and at the same time promotes muscle protein synthesis, improves insulin sensitivity, and promotes glucose metabolism.

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Section: Discussionsupporting

confidence: 48%

Sodium butyrate protects against oxidative stress between obesity-prone and obesity-resistant rats induced by HFD through modulating Nrf2 pathway and mitochondrial function

Lu¹,

Sun²,

Li³

et al. 2020

Preprint

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“…The ratio of adenosine triphosphate (ATP) over adenosine diphosphate (ADP) was measured according to recent papers using the ADP/ATP Ratio Assay Kit (Abcam, UK) following the manufacturer's instructions 60 . BMMSCs were evaluated at 48 h post to RESV or DMSO treatments and shImmt or NC transfection.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Yang

Sui

et al. 2018

Theranostics

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Rational: Senescence of mesenchymal stem cells (MSCs) and the related functional decline of osteogenesis have emerged as the critical pathogenesis of osteoporosis in aging. Resveratrol (RESV), a small molecular compound that safely mimics the effects of dietary restriction, has been well documented to extend lifespan in lower organisms and improve health in aging rodents. However, whether RESV promotes function of senescent stem cells in alleviating age-related phenotypes remains largely unknown. Here, we intend to investigate whether RESV counteracts senescence-associated bone loss via osteogenic improvement of MSCs and the underlying mechanism.Methods: MSCs derived from bone marrow (BMMSCs) and the bone-specific, senescence-accelerated, osteoblastogenesis/osteogenesis-defective mice (the SAMP6 strain) were used as experimental models. In vivo application of RESV was performed at 100 mg/kg intraperitoneally once every other day for 2 months, and in vitro application of RESV was performed at 10 μM. Bone mass, bone formation rates and osteogenic differentiation of BMMSCs were primarily evaluated. Metabolic statuses of BMMSCs and the mitochondrial activity, transcription and morphology were also examined. Mitofilin expression was assessed at both mRNA and protein levels, and short hairpin RNA (shRNA)-based gene knockdown was applied for mechanistic experiments.Results: Chronic intermittent application of RESV enhances bone formation and counteracts accelerated bone loss, with RESV improving osteogenic differentiation of senescent BMMSCs. Furthermore, in rescuing osteogenic decline under BMMSC senescence, RESV restores cellular metabolism through mitochondrial functional recovery via facilitating mitochondrial autonomous gene transcription. Molecularly, in alleviating senescence-associated mitochondrial disorders of BMMSCs, particularly the mitochondrial morphological alterations, RESV upregulates Mitofilin, also known as inner membrane protein of mitochondria (Immt) or Mic60, which is the core component of the mitochondrial contact site and cristae organizing system (MICOS). Moreover, Mitofilin is revealed to be indispensable for mitochondrial homeostasis and osteogenesis of BMMSCs, and that insufficiency of Mitofilin leads to BMMSC senescence and bone loss. More importantly, Mitofilin mediates resveratrol-induced mitochondrial and osteogenic improvements of BMMSCs in senescence.Conclusion: Our findings uncover osteogenic functional improvements of senescent MSCs as critical impacts in anti-osteoporotic practice of RESV, and unravel Mitofilin as a novel mechanism mediating RESV promotion on mitochondrial function in stem cell senescence.

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“…Many previous studies have focused the induction of high-fat diets to metabolic dysfunction by oxidative stress in skeletal muscles 15 – 17 . Recent studies focused more on dietary supplements for antioxidant use in skeletal muscles 18 – 22 . Much concern has been taken about the effect of high-protein diets on obesity 23 – 25 and muscle strength enhancement 26 – 28 .…”

Section: Introductionmentioning

confidence: 99%

Oxidative and anti-oxidative status in muscle of young rats in response to six protein diets

Zhu¹,

Xiao²,

Hao

et al. 2017

Sci Rep

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We investigated the impact of six protein diets on oxidation and anti-oxidation status in the muscle of young rats. Rats were fed six protein diets for 14 days, including casein (control), and proteins isolated from soy, fish, chicken, pork and beef. Grx1, Trx1 and other oxidative metabolic indices in muscle were quantified. Compared with the casein diet, the soy protein diet had a similar oxidation level, but higher GSH and lower SOD activities. The chicken and fish protein groups had lower GSH and higher SOD activities, the pork protein group showed lower Grx1 levels than the casein group and the beef protein group showed the highest GSH, Grx1 and Trx1 levels as reflected by RT-PCR, Western blotting and immunohistochemistry analyses. Intake of meat proteins showed higher ROS and T-AOC but lower MDA levels than non-meat proteins, which may be due to the increase in Grx1 and Trx1 expression and other antioxidants. Meat proteins are more conducive to muscle of growing rats.

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Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle

Cited by 39 publications

References 63 publications

Sodium butyrate protects against oxidative stress between obesity-prone and obesity-resistant rats induced by HFD through modulating Nrf2 pathway and mitochondrial function

Sodium butyrate protects against oxidative stress between obesity-prone and obesity-resistant rats induced by HFD through modulating Nrf2 pathway and mitochondrial function

Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice

Oxidative and anti-oxidative status in muscle of young rats in response to six protein diets

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