Yoshiko Fukuchi

Lemon Polyphenols Suppress Diet-induced Obesity by Up-Regulation of mRNA Levels of the Enzymes Involved in β-Oxidation in Mouse White Adipose Tissue

The aim of this study was to investigate the effect of dietary lemon polyphenols on high-fat diet-induced obesity in mice, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. Mice were divided into three groups and fed either a low fat diet (LF) or a high fat diet (HF) or a high fat diet supplemented with 0.5% w/w lemon polyphenols (LP) extracted from lemon peel for 12 weeks. Body weight gain, fat pad accumulation, the development of hyperlipidemia, hyperglycemia, and insulin resistance were significantly suppressed by lemon polyphenols. Supplementation with lemon polyphenols also significantly up-regulated the mRNA level of the peroxisome proliferator activated receptor-α (PPARα) compared to the LF and HF groups in the liver. Furthermore, the mRNA level of acyl-CoA oxidase (ACO) was up-regulated in the LP group compared to the LF group, but not HF group in the liver, and was also significantly increased in the epididymal white adipose tissue. Thus, feeding with lemon polyphenols suppressed body weight gain and body fat accumulation by increasing peroxisomal β-oxidation through up-regulation of the mRNA level of ACO in the liver and white adipose tissue, which was likely mediated via up-regulation of the mRNA levels of PPARα.

Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice

To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration.

Delayed postprandial metabolism of triglyceride-rich lipoproteins in obese young men compared to lean young men.

BACKGROUND Obesity, especially visceral obesity, has been known to affect lipoprotein metabolism, but it is not clear whether obesity in young, apparently healthy men is associated with postprandial triglyceride-rich lipoprotein (TRL) metabolism. METHODS Ten young normolipidemic, normoglycemic obese men (20.6 ± 0.5 y, BMI 27.5 ± 1.0 kg/m(2)) and 11 lean healthy men (22.1 ± 0.4 y, 21.2 ± 0.4 kg/m(2)) ingested OFTT cream (1g/kg body weight). Fasting and postprandial blood samples were obtained for up to 6h, and serum lipids and lipoproteins were analyzed. RESULTS The obese men with a fasting triglyceride (TG) in the normal range and not different from the fasting value of lean controls had a prolonged postprandial response, indicated by a significantly greater incremental areas under the curve in serum TG, TRL-TG, and remnant-like particle-cholesterol (RLP-C) compared with controls. Plasma glucose levels did not change during the test. Differences in serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) were not statistically significant between the two groups; however, trends toward higher levels were shown in obese young men. CONCLUSIONS The obese young men showed significantly delayed TRL metabolism compared to the lean young men after fat loading, even though the obese men were normolipidemic. These results suggest the possibility that early insulin resistance in the obese young men may have caused the decrease of lipoprotein lipase activity and induced delayed TRL metabolism. A fat loading test without carbohydrate may provide a useful tool for the detection of delayed postprandial TRL metabolism and early insulin resistance.

Use of 13C-labeled glucose for measuring exogenous glucose oxidation in mice.

The author modified a respiratory gas analyzer to analyze the respiratory 13CO2 of 12 small laboratory animals all at once. To investigate the practical use of this system, mice were orally (OR) or intravenously (IV) given glucose solutions containing three different amounts of 13C-labeled glucose. Expired 13CO2 derived from exogenous glucose was detected within 10 minutes after administration in OR mice, but about 30 minutes in IV mice. The height of the peak of 13CO2 expiration was correlated with the administered 13C-glucose mass.

Immunochemical detection of flavonoid glycosides: Development, specificity, and application of novel monoclonal antibodies

Flavonoid-rich diets are expected to decrease the risk of cardiovascular diseases. The localization and target sites of flavonoids underlying the protective mechanism in vivo have not been fully investigated because the methods for detection of flavonoids have been limited to chemical analysis such as high-performance liquid chromatography. To further understand the actions of flavonoids in vivo, we developed a novel methodology that immunochemically evaluates flavonoids using specific antibodies. Quercetin-3-glucuronide (Q3GA), a major metabolite in human plasma, was coupled with keyhole limpet hemocyanin. Alternatively, the sugar moiety of quercetin-3-glucoside (Q3G) was succinylated and then coupled with a carrier protein. Using these two immunogens, we finally obtained two monoclonal antibodies, mAb14A2 and mAb11G6, from the immunogen using Q3GA and Q3G, respectively. Competitive enzyme-linked immunosorbent assay showed the unique difference in the specificity between the two similar antibodies: mAb14A2 recognized several quercetin-3-glycosides including Q3G and rutin but mAb11G6 was highly specific to the Q3G structure. The macrophage-derived foam cells in human atherosclerotic lesions were significantly stained with mAb14A2 but scarcely with mAb11G6. These results showed that the anti-flavonoid glycoside antibodies are useful tools for evaluating their localization in tissues and that the specificities strongly depend on the immunogen design for synthesizing the hapten-protein conjugates.

Amino Acid Composition of Soybean Protein Increased Postprandial Carbohydrate Oxidation in Diabetic Mice

The effects of an amino acid mixture simulating dietary soybean protein on the postprandial energy metabolism was investigated using type II diabetic mice. KK-Ay strain mice were fed restrictive isoenergetic and isonitrogenous diets (35% of energy as protein and 5% as fat) based on either casein, soybean protein isolate hydrolysate (SPI-H), SPI-HET (ethanol unsoluble fraction of SPI-H), SPI-AA and casein-AA (amino acid mixtures simulating SPI-H and casein). To measure dietary carbohydrate oxidation, the animals were fed a diet containing 13C-glucose. Postprandial respiratory quotient and expired 13CO2 were higher in the SPI-AA than in the casein-AA group, as the differences were similarly observed in mice fed SPI-H and casein diet. No significant differences were observed in the postprandial respiratory quotient and expired 13CO2 between the SPI-H and SPI-HET group. In conclusion, this study on food-restricted mice indicates that the amino acid mixtures simulating SPI-H or casein could affect postprandial energy metabolism in diabetic mice, as observed in those fed SPI-H or casein in the form of peptide or protein.