Background: Mitochondrial dysfunction is associated with obesity and various obesity-associated pathological\nconditions including glucose intolerance. 5-Aminolevulinic acid (ALA), a precursor of heme metabolites, is a natural\namino acid synthesized in the mitochondria, and various types of cytochromes containing heme contribute to aerobic\nenergy metabolism. Thus, ALA might have beneficial effects on the reduction of adiposity and improvement of glucose\ntolerance through its promotion of heme synthesis. In the present study, we investigated the effects of ALA combined\nwith sodium ferrous citrate (SFC) on obesity and glucose intolerance in diet-induced obese mice.\nMethods: We used 20-weeks-old male C57BL/6J diet-induced obesity (DIO) mice that had been fed high-fat diet from\n4th week or wild-type C57BL/6J mice. The DIO mice were orally administered ALA combined with SFC (ALA/SFC) for\n6 weeks. At the 4th and 5th week during ALA/SFC administration, mice were fasted for 5 h and overnight, respectively\nand used for oral glucose tolerance test. After the ALA/SFC administration, the plasma glucose levels, weight of white\nadipose tissue, and expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes were examined.\nFurthermore, the effects of ALA/SFC on lipid content and glucose uptake were examined in vitro.\nResults: Oral administration of ALA/SFC for 6 weeks reduced the body weight by about 10% and the weight of white\nadipose tissues in these animals. In vitro, ALA/SFC reduced lipid content in mouse 3T3-L1 adipocytes in a\ndose dependent manner, and enhanced glucose uptake in 3T3-L1 adipocytes by 70ââ?¬â??90% and rat L6 myoblasts by 30% at\n6 h. Additionally, oral administration of ALA/SFC reduced plasma glucose levels and improved glucose tolerance in DIO\nmice. Furthermore, ALA/SFC enhanced the expression of OXPHOS complexes III, IV, and V by 40ââ?¬â??70% in white adipose\ntissues of DIO mice, improving mitochondrial function.\nConclusions: Our findings indicate that ALA/SFC is effective in the reduction of adiposity and improvement of glucose\ntolerance, and that the induction of mitochondrial OXPHOS complex III, IV, and V by ALA/SFC might be an essential\ncomponent of the molecular mechanisms underlying these effects. ALA/SFC might be a useful supplement for obesity\nand obesity-related metabolic disease such as type 2 diabetes mellitus.
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