Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats

Abstract

BackgroundType 2 diabetes is characterized by dyslipidemia and the accumulation of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a natural isoflavonoid isolated from the root of the plant Pueraria lobata, has been shown to have antidiabetic activity. However, the lipid-reducing effect of puerarin, in particular in skeletal muscle, has not yet been addressed.MethodsWe examined the effect of puerarin on mitochondrial function and the oxidation of fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced diabetic rats.ResultsPuerarin effectively alleviated dyslipidemia and decreased the accumulation of intramyocellular lipids by upregulating the expression of a range of genes involved in mitochondrial biogenesis, oxidative phosphorylation, the detoxification of reactive oxygen species, and the oxidation of fatty acids in the muscle of diabetic rats. Also, the effect of puerarin on mitochondrial biogenesis might partially involve the function of the μ-opioid receptor. In addition, puerarin decreased the trafficking of fatty acid translocase/CD36 to the plasma membrane to reduce the uptake of fatty acids by myocytes. In vitro studies confirmed that puerarin acted directly on muscle cells to promote the oxidation of fatty acids in insulin-resistant myotubes treated with palmitate.ConclusionsPuerarin improved the performance of mitochondria in muscle and promoted the oxidation of fatty acids, which thus prevented the accumulation of intramyocellular lipids in diabetic rats. Our findings will be beneficial both for elucidating the mechanism of the antidiabetic activity of puerarin and for promoting the therapeutic potential of puerarin in the treatment of diabetes.

Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy

“…PR has been reported to possess anti-oxidative, hypotensive and hypoglycaemic activities [13][14][15]. Prior studies have demonstrated that PR exerted protective effects on diabetic kidney injury, heart failure, diabetic cardiomyopathy, cardiac fibroblast proliferation, skeletal muscle energy metabolism and liver lipid metabolism [16][17][18][19][20][21][22]. The hypoglycaemic effect of PR on diabetes mellitus was confirmed by previous studies [15,23,24].…”

Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

“…In addition, flavonoid-induced protection has been demonstrated in various models of human diseases. For example, the induction of mitochondrial biogenesis by baicalein reverses mitochondrial dysfunction in a Parkinson's disease model, puerarin improves mitochondrial performance in diabetic rats, quercetin is beneficial in osteoarthritis and traumatic brain injury models, and dihydromycetin ameliorates cardiac I/R injury [174][175][176][177][178].…”

Does the Energy Restriction Intermittent Fasting Diet Alleviate Metabolic Syndrome Biomarkers? A Randomized Controlled Trial

“…Organizations such as the National Heart, Lung, and Blood Institute (NHLBI), the American Heart Association (AHA), the World Health Organization (WHO), the National Cholesterol Education Adult Treatment (NCEP-ATP III), and the International Diabetes Federation (IDF) have proposed diverse diagnostic criteria and cut-off values for MetS [ 3 , 4 , 5 ]. Depending on the difference in the diagnostic criteria used, the incidence of metabolic syndrome in adults in varied populations has been reported to range from 28 to 50% [ 6 , 7 , 8 , 9 , 10 ]. Turkey, whose adult obesity prevalence is 28.8%, is in the top ten of the adult obesity prevalence ranking in Organization for Economic Cooperation and Development (OECD) countries [ 11 ].…”