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MOTS-c Vascular Calcification and Insulin Resensitization

“product By Nemo 3 months ago

AMPK Activation Targets Vascular Calcification and Metabolic Homeostasis

"Recently, MOTS-c, a novel bioactive mitochondrial-derived peptide, has been demonstrated to activate the AMPK pathway to promote metabolic homeostasis... Our findings provide evidence that MOTS-c may act as an inhibitor of VC [Vascular Calcification] by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors." (1)

"Angiotensin II type 1 (AT-1) and endothelin B (ET-B) have been found to be involved in the AMPK pathway by binding to the AT-1 and ET-B receptors, respectively. A decreased level of the AT-1 receptor plays roles in reducing oxidative stress and preventing the development of myocardial contractile dysfunction, while a high level of the AT-1 receptor induces myocardial fibrosis and cardiac dysfunction. AT-1 can induce the relocation and suppression of the AMPK pathway via the AT-1 receptor in the development of diabetic proteinuria. After treatment with metformin, AMPK signaling is activated and AT-1 levels are decreased in the kidney. In epithelial ovarian carcinoma, ET-1 plays a role in epithelial-mesenchymal transition. A decrease in ET-1 receptor activation is beneficial in attenuating biventricular remodeling, and the overexpression of ET-1 causes sustained blood pressure elevation and vascular and renal injury. The activation of the AMPK pathway can also upregulate the ET-B receptor to inhibit autophagy in vascular smooth muscle cells under high glucose conditions." (1)

"Previous reports have shown that MOTS-c can amplify glucose uptake, inhibit the folate cycle and de novo purine biosynthesis following metabolic stress, and regulate nuclear gene expression in an AMPK-dependent manner. MOTS-c treatment dramatically reduced the number of disordered elastic fibers and significantly improved vascular wall structure (Fig. 2c). Moreover, MOTS-c also significantly reduced VDN [Vitamin D3 plus Nicotine] induced calcium phosphate salt deposition in the calcified aortas, as detected by alizarin red S staining and von Kossa staining... Our results showed that MOTS-c reverses VDN-induced AMPK downregulation. In mice with hypoxia-induced pulmonary hypertension, the activation of the AMPK pathway can effectively improve right ventricular systolic pressure and right ventricular hypertrophy due to treatment with liraglutide." (1)

Vasodilation of Calcified Vascular System

"MOTS-c (5 mg/kg) reduced vascular tension and improved echocardiographic parameters under VC [Vascular Calcification] conditions... The vascular tension in the VDN group was significantly reduced compared with that in the control group and the VDN + MOTS-c intervention group (p < 0.01)." (1)

Blood pressure was reduced from 126.25±5.65 over 95.38±3.16 in the Vitamin D3 plus Nicotine Group to 108.20±6.38 over 78.20±9.36 in the Vitamin D3 plus Nicotine & MOTS-c group.

Insulin Receptor Resensitization

"...we performed hyperinsulinemic-euglycemic clamp studies to quantify the effects of a 7-day MOTS-c treatment on whole body insulin sensitivity independent of changes in body weight that occur with extended treatment durations (Figure 5B-D and Table S3). MOTS-c improved whole body insulin sensitivity as reflected by a ∼30% increase in the exogenous glucose infusion rate (GIR) required to maintain euglycemia during insulin stimulation (Figure 5B). (2)

"Although MOTS-c treatment had no effect on body weight in mice fed a normal diet, it remarkably prevented obesity when administrated to mice fed a high fat diet (Figure 6A). Additionally, MOTS-c treatment prevented HFD-induced hyperinsulinemia, indicating improved glucose homeostasis (Figure 6D-E). Hepatic lipid accumulation was dramatically reduced in HFD-fed mice treated with MOTS-c (Figure 6F)." (2)

Sourcing Studies:

(1) Karger.com. (2020). [online] Available at: https://www.karger.com/Article/FullText/503224 [Accessed 9 Mar. 2020].Karger.com. (2020). [online] Available at:https://www.karger.com/Article/FullText/503224

(2) Lee, C., Zeng, J., Drew, B.G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S.-J., Mehta, H., Hevener, A.L., de Cabo, R. and Cohen, P. (2015). The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Cell Metabolism, [online] 21(3), pp.443–454. Available at: https://www.cell.com/article/S1550-4131(15)00061-3/abs

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MOTS-c 10mg

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