Volume 27, Issue 4 (6-2020)                   RJMS 2020, 27(4): 122-130 | Back to browse issues page

Research code: طرح پژوهشی نبوده
Ethics code: 51707

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angouti M, rajabi H, gharakhanlou R, Dehkhoda M. The Effect of Aerobic Training and Intake of L-Carnitine on Mitochondrial Malonyl-CoA and CPT2 Enzymes in Diabetic Wistar Rats.. RJMS 2020; 27 (4) :122-130
URL: http://rjms.iums.ac.ir/article-1-6084-en.html
kharazmi university , hrajabi1346@gmail.com
Abstract:   (2426 Views)

Background: Diabetes is known as one of the diseases that has imposed many health, social and economic problems on human societies and has spread widely in recent decades (1). Glucose metabolism and related disorders for the central nervous system (CNS) and astrocytes, which are the most important glial cells of the central nervous system; It is important. Therefore, disorders of the hypothalamus, cerebral cortex and hippocampus, vascular disorders of the brain, etc. are among the complications of diabetes on the central nervous system (3). Among the brain regions, the hippocampus is one of the most sensitive areas that is vulnerable to harmful factors such as ischemia, stress and especially diabetes, during which it undergoes neurophysiological, structural and molecular changes such as decreased neurogenesis 3 and atrophy. Hippocampus (4), which leads to one of the significant changes caused by diabetes, namely neuronal death in the hippocampus (5).
Due to the fact that insulin resistance and type 2 diabetes are characterized by hyperglycemia, hyperinsulinemia, increased plasma FFA levels, decreased fat oxidation ability and fat accumulation in body cells (6). And this increase in fat content has a high relationship with insulin resistance and the main cause of this accumulation of fat is mitochondrial dysfunction (7). Two mitochondrial enzymes that are important in the fat metabolism of cells in the body are Malonyl-CoA and CPT2. Malonyl-CoA, a coenzyme derived from malonic acid, plays an essential role in the transport of fatty acids into the mitochondria and in their synthesis. Are fatty acids (8). Accordingly, some evidence suggests that reducing the amount of malonyl coenzyme A reduces insulin resistance (10).In this regard, carnitine palmitol transferase 2 is a mitochondrial protein that is attached to the inner part of the mitochondrial membrane and plays a key role in the transport of fatty acids into the cell for beta oxidation (11). The regulation of CPT-2 activity by Malonyl-CoA or other metabolic mediators is not directly or indirectly known (12). One of the supplements that has been shown to facilitate beta oxidation of long chain fatty acids and participate in the metabolism of branched-chain amino acids and fix cell membranes is L-carnitine (14). Due to the fact that L-carnitine is able to transport the acetate group from the mitochondria to the cytoplasm, thereby reducing the ratio of acetyl coenzyme A to coenzyme A in the mitochondria, thereby increasing the activity of the enzyme pyruvate dihydrogenase and thus glucose catabolism. Give (15). Therefore, taking this supplement may be able to improve mitochondrial disorders caused by diabetes in various tissues, including nerve tissue.
On the other hand, in addition to nutrition and various supplements, physical activity and exercise have been proposed as a way to control diabetes disorders (16). In confirmation of this, exercise activity in diabetic rats by reducing blood sugar levels, causes cell proliferation and increases the synaptic plasticity of neurons in the hippocampus of the brain (17). In fact, exercise creates endogenous neuroprotection by reducing endogenous neurons and protecting them against diabetic neuropathy, and ultimately reducing diabetic cognitive and motor disorders (18), thus increasing activity. Regular exercise can improve the malleability of the brain (19), the antioxidant system (20), and the upregulation of neurotrophins (21).
Considering the above and considering the negative effects of diabetes on various body systems on the one hand and irreparable damage to society, researchers are always looking to discover the best way to prevent and treat this dangerous complication. Various studies have been performed on the effect of increased plasma L-carnitine on FFA intake or exercise endurance capacity following oral administration or intravenous injection; In this regard, some findings suggest that L-carnitine supplementation increases fat oxidation (25) decreases carbohydrate oxidation (26) improves exercise (27) and reduces recovery time following exercise (28) Leads. Given the above and differences in research results on the effect of aerobic exercise and L-carnitine on mitochondrial disorders on the one hand and the lack of research on the subject of research on the hippocampus on the other hand and discovering a way to minimize the negative effects of diabetes Specifically, the increase in cellular fat content in the hippocampus, the researcher seeks to answer the question of whether increased aerobic activity and consumption of L-carnitine have an effect on mitochondrial factors in the hippocampus of diabetic rats or not?
Methods: This research is of developmental type and its method is experimental. In which the ethical principles of working with laboratory animals, such as the availability of water and food, and proper storage conditions, and how to kill mice were observed.
The statistical population of the present study consisted of male Wistar rats in the weight range of 250 to 300 g and 6 to 8 weeks of age that were bred at the Razi Serum Laboratory Animal Breeding Center. From the statistical population, 45 rats were randomly selected as a statistical sample and randomly divided into 6 groups. Groups include 1) sham injection group (5 rats), 2) healthy control (8 rats), 3) diabetic control group (8 rats), 4) diabetic group receiving L-carnitine (8 rats), 5) The diabetic group was aerobic exercise (8 rats) 6) The diabetic group was aerobic exercise and received L-carnitine (8 rats). In the diabetic group, animals became diabetic by injecting streptozotocin (STZ) at 55 mg / kg body weight. 48 hours after STZ injection, hyperglycemia was confirmed by glucose oxidase assay with biosystem kit. Thus, rats with serum glucose above 300 mg / dL were considered diabetic. In the diabetic and exercise groups, the animals ran on a treadmill for six weeks after induction of diabetes. Rats receiving L-carnitine received 100 mg of L-carnitine (29, 30) orally daily for 6 weeks. Aerobic exercise groups also performed a training program including aerobic exercise on a treadmill, 5 days a week, from 9 am to 11 am, for 6 weeks (31).
Results: In the present study, the effect of aerobic exercise and consumption of L-carnitine on the mitochondrial CPT2 content of hippocampal tissue was observed (p= 0.008). However, there was no significant difference in the number of Malonyl-CoA mitochondria in the hippocampal tissue of diabetic rats as a result of aerobic exercise and L-carnitine administration (p= 0.227). The effect of aerobic exercise and alcarnitine consumption on Malonyl-CoA and CPT2 enzymes in the hippocampal tissue of diabetic rats was investigated. Based on the results of Tukey post hoc test, it was shown that diabetes is associated with a significant increase in Malonyl-CoA mitochondria of hippocampal tissue. Consistent with a study by Badiopada et al. (2006) that increased Malonyl-CoA levels and decreased fatty acid oxidation showed key abnormalities in insulin resistance in type 2 diabetic specimens (32).
 In general, exercise can stimulate lipid oxidation and inhibit lipid synthesis in the liver, a process that is mediated by activation of the AMPK pathway (33). However, as the results of the present study show, the response of Malonyl-CoA to exercise is different in hippocampal tissue, so it is possible that Malonyl-CoA levels in different tissues respond differently to exercise. The lack of significant change in Malonyl-CoA levels in the hippocampal tissue of diabetic specimens and the aerobic exercise program with L-carnitine can be attributed to changes in tissue insulin sensitivity and tissue oxidation. In the present study, the interaction between aerobic exercise and L-carnitine consumption had no effect on Malonyl-CoA hippocampus in rats. Although there are several mechanisms involved in supporting the effects of exercise on diabetes, the type of exercise and the dose of L-carnitine supplementation can also affect the results. Therefore, further studies are needed to discover the mechanism of Malonyl-CoA changes in the hippocampus, especially in diabetic specimens following L-carnitine exercise and consumption.
The present study showed that diabetes was associated with a significant decrease in hippocampal tissue CPT2 index and the results showed that aerobic exercise and L-carnitine consumption had no effect on rat hippocampal CPT2. But the interaction of aerobic exercise and supplementation significantly increased CPT2 in the rat hippocampus. The palmitoyl carnitine transferase (CPT) system contains two enzymes, CPT I and CPT II, and are involved in the transport of long-chain fatty acids into the mitochondrial compartment. The enzymes are CPT I in the outer membrane and CPT II in the inner membrane of the mitochondria (11). The results of Aminizadeh et al. (2017) on the regulation of cellular energy homeostasis in the skeletal muscle of male rats after four weeks of endurance training showed that the expression of carnitine palmityl transferase 1 beta gene in the endurance training group was significantly higher than the control group (34). However, the exact mechanisms of the effect of exercise on CPT II regulation in hippocampal tissue are not well understood. Also, the physiological significance of the natural inhibition of CPT II by malonyl coa has not been determined. However, due to the high sensitivity of CPT II to Malonyl-CoA, it can be stated that changes in CPT II level are dependent on the level of Malonyl-CoA (35).
Conclusion: Due to the effect of aerobic exercise and L-carnitine supplement alone and in interaction, using them in consultation with a physician is recommended for diabetics.

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Type of Study: Research | Subject: Exercise Physiology

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