5-Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high-fat diet-fed mice via upregulation of glucose transporter 1.

Decreased mitochondrial metabolism suppresses glucose metabolism, resulting in obesity and diabetes. The present study aimed to investigate mechanisms underlying the 5-aminolevulinic acid (5-ALA) hydrochloride-mediated increase in glucose uptake in high-fat diet (HFD)-fed mice in vivo and C2C12 myotube cells in vitro. C57BL/6N male mice (20 weeks old) were fed either HFD or normal diet (ND) for 4 weeks. A total of five HFD-fed mice were orally administered with 300 mg/kg 5-ALA hydrochloride and 47.1 mg/kg sodium ferrous citrate (SFC; HFD + 5-ALA/SFC), whereas ND and other HFD-fed mice were orally administered with saline. After 4 weeks, these mice were intraperitoneally administered with 2 g/kg glucose and 3.2 mg/kg 2-deoxyglucose (2DG) for intraperitoneal glucose tolerance test (IPGTT) and glucose uptake test. Body weights, plasma glucose levels and the area under the curve of IPGTT were lower in mice treated with HFD + 5-ALA/SFC compared with in those treated with HFD alone. 2DG uptake in the gastrocnemius muscle and heart were more significantly improved in the HFD + 5-ALA/SFC mice compared with the HFD-fed mice. Furthermore, 5-ALA/SFC increased 2DG uptake in C2C12 cells to a similar level to the insulin-treated group. Moreover, it increased glucose transport (GLUT)1 translocation in the plasma membrane by 2.5-fold relative to the controls without affecting GLUT1 expression; however, it had no effect on GLUT4 translocation. Therefore, 5-ALA/SFC enhanced gastrocnemius and cardiac glucose uptake in HFD-fed mice, and upregulated GLUT1 translocation to the plasma membrane, but not GLUT4 in C2C12 myotube cells. Therefore, it could potentially be used as a novel drug for the treatment of diabetes.

5-Aminolevulinic acid with ferrous iron improves early renal damage and hepatic steatosis in high fat diet-induced obese mice.

5-Aminolevulinic acid, a natural amino acid, activates mitochondrial respiration and induces heme oxygenase-1 expression. Obesity and type 2 diabetes mellitus are associated with age-related mitochondrial respiration defect, oxidative stress and inflammation. The aim of this study is to investigate the effects of 5-aminolevulinic acid with sodium ferrous citrate on early renal damage and hepatic steatosis. 7-Month-old C57BL/6 mice were fed with a standard diet or high fat diet for 9 weeks, which were orally administered 300 mg/kg 5-aminolevulinic acid combined with 47 mg/kg sodium ferrous citrate (5-aminolevulinic acid/sodium ferrous citrate) or vehicle for the last 5 weeks. We observed that 5-aminolevulinic acid/sodium ferrous citrate significantly decreased body weight, fat weight, hepatic lipid deposits and improved levels of blood glucose and oral glucose tolerance test. In addition, 5-aminolevulinic acid/sodium ferrous citrate suppressed increased glomerular tuft area in high fat diet-fed mice, which was associated with increased heme oxygenase-1 protein expression. Our findings demonstrate additional evidence that 5-aminolevulinic acid/sodium ferrous citrate could improve glucose and lipid metabolism in diabetic mice. 5-Aminolevulinic acid/sodium ferrous citrate has potential application in obesity or type 2 diabetes mellitus-associated disease such as diabetic nephropathy and nonalcoholic fatty liver disease.

5-aminolevulinic acid combined with ferrous ion reduces adiposity and improves glucose tolerance in diet-induced obese mice via enhancing mitochondrial function.

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

High-pressure generation using double stage micro-paired diamond anvils shaped by focused ion beam.

Micron-sized diamond anvils with a 3 µm culet were successfully processed using a focused ion beam (FIB) system and the generation of high pressures was confirmed using the double stage diamond anvil cell technique. The difficulty of aligning two second-stage micro-anvils was solved via the paired micro-anvil method. Micro-manufacturing using a FIB system enables us to control anvil shape, process any materials, including nano-polycrystalline diamond and single crystal diamond, and assemble the sample exactly in a very small space between the second-stage anvils. This method is highly reproducible. High pressures over 300 GPa were achieved, and the pressure distribution around the micro-anvil culet was evaluated by using a well-focused synchrotron micro-X-ray beam.

Hybrid Cu(x)O/TiO2 nanocomposites as risk-reduction materials in indoor environments.

Photocatalytic TiO(2) powders impart ultraviolet light-induced self-cleaning and antibacterial functions when coated on outdoor building materials. For indoor applications, however, TiO(2) must be modified for visible-light and dark sensitivity. Here we report that the grafting of nanometer-sized Cu(x)O clusters onto TiO(2) generates an excellent risk-reduction material in indoor environments. X-ray absorption near-edge structure using synchrotron radiation and high-resolution transmission electron microscopic analyses revealed that Cu(x)O clusters were composed of Cu(I) and Cu(II) valence states. The Cu(II) species in the Cu(x)O clusters endow TiO(2) with efficient visible-light photooxidation of volatile organic compounds, whereas the Cu(I) species impart antimicrobial properties under dark conditions. By controlling the balance between Cu(I) and Cu(II) in Cu(x)O, efficient decomposition and antipathogenic activity were achieved in the hybrid Cu(x)O/TiO(2) nanocomposites.

Evaluation of TEM samples of an Mg-Al alloy prepared using FIB milling at the operating voltages of 10 kV and 40 kV.

Transmission electron microscopy (TEM) samples of an Mg-Al alloy has been prepared using a Ga-focused ion beam (FIB) milling at two different operating voltages of 10 kV and 40 kV to investigate the influence of the FIB energy on the sample quality. The fine structures of the samples have been studied using a high resolution TEM, and the concentration of the implanted Ga was analysed using an energy dispersive X-ray (EDX) analysis. The result of the TEM observation revealed that point defects were introduced to the sample finally milled at 40 kV but not at 10 kV. However, crystal lattice images and electron diffraction patterns were clearly observed on both the samples. The typical influence of the FIB energy was indicated in the elemental analysis. The relative Ga concentration in the thin sample finally milled at 10 kV was 1.0-2.0 at% that is less than half of 4.0-6.0 at% of the Ga concentration in the sample finally milled at 40 kV. A comparison between the experimental results of the Ga concentration measurement with simulation was also discussed.