L-Carnosine Stimulation of Coenzyme Q10 Biosynthesis Promotes Improved Mitochondrial Function and Decreases Hepatic Steatosis in Diabetic Conditions.

Cheng Schwank-Xu,Michael Tekle,Ishrath Ansurudeen,Kerstin Brismar,Allan Zhao,Magnus Bentinger,Elisabete Forsberg,Gustav Dallner,Sergiu-Bogdan Catrina

doi:10.3390/antiox10050793

Cheng Schwank-Xu, Michael Tekle + Show 7 more

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https://doi.org/10.3390/antiox10050793

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Abstract

Mitochondrial dysfunction in type 2 diabetes leads to oxidative stress, which drives disease progression and diabetes complications. L-carnosine, an endogenous dipeptide, improves metabolic control, wound healing and kidney function in animal models of type 2 diabetes. Coenzyme Q (CoQ), a component of the mitochondrial electron transport chain, possesses similar protective effects on diabetes complications. We aimed to study the effect of carnosine on CoQ, and assess any synergistic effects of carnosine and CoQ on improved mitochondrial function in a mouse model of type 2 diabetes. Carnosine enhanced CoQ gene expression and increased hepatic CoQ biosynthesis in db/db mice, a type 2 diabetes model. Co-administration of Carnosine and CoQ improved mitochondrial function, lowered ROS formation and reduced signs of oxidative stress. Our work suggests that carnosine exerts beneficial effects on hepatic CoQ synthesis and when combined with CoQ, improves mitochondrial function and cellular redox balance in the liver of diabetic mice. (4) Conclusions: L-carnosine has beneficial effects on oxidative stress both alone and in combination with CoQ on hepatic mitochondrial function in an obese type 2 diabetes mouse model.

Highlights

electron spin resonance spectrometry (EPR) spectra for cells treated with sham treated and untreated control (C57B) and db/db mice
As coenzyme Q (CoQ) is known to have beneficial effects on mitochondrial function, we further studied the effect of CRN on oxygen consumption rate (OCR) in HepG2 cells using cell respirometry (Figure 3A)
We showed that CRN induces in the liver biosynthesis of CoQ in diaIn this work, we showed that CRN induces in the liver biosynthesis of CoQ in diabetic betic conditions and that it directly upregulates the PDSS1 and COQ2 genes, which enconditions and that it directly upregulates the PDSS1 and COQ2 genes, which encode code rate-limiting enzymes in endogenous de novo CoQ biosynthesis [8]

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The beneficial effects of L-carnosine (CRN), a dipeptide (β-alanyl-L-histidine), and coenzyme Q (CoQ), a neutral lipid, have been studied in the context of antioxidant functions with increasing interest in recent years. CRN and CoQ are potent endogenous antioxidants with anti-inflammatory properties, and have a potential role in the preventive treatment of diabetes complications [1]. Our laboratory has previously explored the beneficial effects of CRN in the db/db mouse model of type 2 diabetes [2]

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