CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats

Ma, Zhen‐Guo; Yao, Yuan; Xu, Si-Chi; Wei, Wenying; Xu, Chunru; Zhang, Xin; Wu, Qin; Liao, Hai-Han; Ni, Jian; Tang, Qi‐Zhu

doi:10.1007/s00125-017-4232-4

Cited by 130 publications

(136 citation statements)

References 48 publications

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“…Animals were maintained under a controlled temperature (22 ± 2°C) with a 12‐hour light/dark cycle. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg/d) . Control animals received an intraperitoneal injection of vehicle only.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way

et al. 2020

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Aim: Imbalanced mitochondrial dynamics including suppressed mitochondrial fusion has been observed in diabetic hearts. However, it is still unknown whether mitochondrial fusion promoter is an effective protection to diabetic hearts. This study was designed to explore the efficacy of mitochondrial fusion promoter on diabetic cardiomyopathy (DCM). Methods: Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg/d) intraperitoneally to induce diabetes. Seven weeks after vehicle or STZ injection, control or diabetic rats were treated with the vehicle or a mitochondrial fusion promoter-M1 (2 mg/kg/d) intraperitoneally for 6 weeks. Moreover, M1 was administrated to the primary cardiomyocytes cultured in normal glucose medium (NG, 5.5 mmol/L) or high glucose (HG, 33 mnol/L). Results: Administration of M1 significantly promoted mitochondrial fusion and attenuated the reduction in optic atrophy 1 (Opa1) expression in diabetic hearts. Importantly, M1 treatment attenuated oxidative stress, improved mitochondrial function and alleviated DCM in diabetic rats. In HG-treated cardiomyocytes, M1 treatment consistently increased the expression of Opa1, promoted mitochondrial fusion, enhanced mitochondrial respiratory capacity and reduced mitochondria-derived superoxide production, all of which were blunted by Opa1 siRNA knockdown. In addition, selective upregulation of Opa1 alone can also promote mitochondrial fusion, improve mitochondrial function and inhibit mitochondria-derived superoxide production in HG-cultured cardiomyocytes. Conclusion: Our findings show for the first time that mitochondrial fusion promoter M1 effectively balances mitochondrial dynamics and protects against diabetic cardiomyopathy (DCM) via an Opa1-dependent way, suggesting that promoting mitochondrial fusion might be a potential therapeutic strategy for DCM. K E Y W O R D Sdiabetes, diabetic cardiomyopathy, mitochondrial fusion, Opa1, oxidative stress 2 of 14 | DING et al.

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Section: Methodsmentioning

confidence: 99%

Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way

et al. 2020

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“…AMPK, in addition to the metabolic and anti-inflammatory effects described above, may function in responding to oxidative stress. AMPKα is activated by adiponectin and the novel adipokine C1q/tumour necrosis factor-related protein-3 (CTRP3) which provides protection from hyperglycemia induced oxidative stress, inflammation, and apoptosis in vitro 112 . Both CTRP3 and adiponectin belong to the C1q/TNF superfamily CTRP3 and suppress hepatic gluconeogenesis 113 and are decreased with obesity 114 .…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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“…Diabetic cardiomyopathy (DCM) is the primary cause of overt heart failure and death in diabetic individuals and affects nearly 12% of diabetic patients . Ma et al recently report that the heart failure rate in patients with diabetes is four times that in people without diabetes . Strategies regulating blood glucose cannot effectively inhibit the incidence of DCM and improve cardiac dysfunction .…”

Section: Introductionmentioning

confidence: 99%

Gypenosides improve diabetic cardiomyopathy by inhibiting ROS‐mediated NLRP3 inflammasome activation

Zhang

Chen

Zong

et al. 2018

J Cellular Molecular Medi

107

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NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti‐hyperglycaemia and anti‐inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL‐1β and IL‐18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome c dramatically down‐regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C‐reactive proteins (CRPs), IL‐1β and IL‐18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS‐mediated NLRP3 inflammasome activation.

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CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats

Abstract: CTRP3 protected against DCM via activation of the AMPKα pathway. CTRP3 has therapeutic potential for the treatment of DCM.

Cited by 130 publications

References 48 publications

Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way

Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way

Macrophage functions in lean and obese adipose tissue

Gypenosides improve diabetic cardiomyopathy by inhibiting ROS‐mediated NLRP3 inflammasome activation

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