BackgroundObesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain.MethodsC57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro.ResultsSudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.ConclusionsSudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.

Long-term suppression of postprandial glucose concentration is an important dietary strategy for the prevention and treatment of type 2 diabetes. Because previous reports have suggested that seaweed may exert anti-diabetic effects in animals, the effects of Wakame or Mekabu intake with 200 g white rice, 50 g boiled soybeans, 60 g potatoes, and 40 g broccoli on postprandial glucose, insulin and free fatty acid levels were investigated in healthy subjects. Plasma glucose levels at 30 min and glucose area under the curve (AUC) at 0-30 min after the Mekabu meal were significantly lower than that after the control meal. Plasma glucose and glucose AUC were not different between the Wakame and control meals. Postprandial serum insulin and its AUC and free fatty acid concentration were not different among the three meals. In addition, fullness, satisfaction, and wellness scores were not different among the three meals. Thus, consumption of 70 g Mekabu with a white rice-based breakfast reduces postprandial glucose concentration.

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The izumi shrimp (Plesionika izumiae Omori, 1971) is an unused resource which can be caught off the southern coast of Tokushima Prefecture. We have previously found that an izumi shrimp hydrolysate significantly inhibited the age-associated spontaneous increase in blood pressure in stroke-prone spontaneously hypertensive rats. In this present study, two angiotensin I-converting enzyme inhibitory peptides were isolated from an izumi shrimp hydrolysate by using high-performance liquid chromatography, and their amino acid sequences were determined to be ValTrp-Tyr-His-Thr and Val-Trp. A single oral administration of synthetic Val-Trp-Tyr-His-Thr or Val-Trp significantly decreased the blood pressure in strokeprone spontaneously hypertensive rats. The antigenicity and allergenicity of the izumi shrimp hydrolysate against BALB/c mice were very low. These results demonstrate that the angiotensin I-converting enzyme inhibitory peptides isolated from the izumi shrimp hydrolysate had an anti-hypertensive effect on rats.

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Scope Polymethoxylated flavones (PMFs) are a group of natural compounds known to display a wide array of beneficial effects to promote physiological fitness. Recent studies reveal circadian clocks as an important cellular mechanism mediating preventive efficacy of the major PMF Nobiletin against metabolic disorders. Sudachitin is a PMF enriched in Citrus sudachi, and its functions and mechanism of action are poorly understood. Methods and results Using circadian reporter cells, it shows that Sudachitin modulates circadian amplitude and period of Bmal1 promoter‐driven reporter rhythms, and real‐time qPCR analysis shows that Sudachitin alters expression of core clock genes, notably Bmal1, at both transcript and protein levels. Mass‐spec analysis reveals systemic exposure in vivo. In mice fed with high‐fat diet with or without Sudachitin, it observes increased nighttime activity and daytime sleep, accompanied by significant metabolic improvements in a circadian time‐dependent manner, including respiratory quotient, blood lipid and glucose profiles, and liver physiology. Focusing on liver, RNA‐sequencing and metabolomic analyses reveal prevalent diurnal alteration in both gene expression and metabolite accumulation. Conclusion This study elucidates Sudachitin as a new clock‐modulating PMF with beneficial effects to improve diurnal metabolic homeostasis and liver physiology, suggesting the circadian clock as a fundamental mechanism to safeguard physiological well‐being.

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SummaryShirasuboshi (boiled and semi-dried whitebait) is a processed fish food that con tains abundant calcium. It is eaten whole and commonly consumed in Japan. In this study, the effect of sudachi (Citrus sudachi) juice on calcium, magnesium and phosphorus bioavail ability, and bone metabolism in rats was examined. After 14 d of diets low in calcium and phosphorus, male Sprague-Dawley rats were fed shirasuboshi diets containing dried shira suboshi powder treated with 20% (S20) or 40% (S40) sudachi juice, or distilled water (C) (0.5% Ca; 0.3% P) for 14 d. The apparent absorptions and retentions of calcium, magne sium and phosphorus from shirasuboshi were determined. Bone formation was calculated by measuring serum osteocalcin, and bone resorption by measuring urinary pyridinoline and deoxypyridinoline. The apparent absorption and retention of calcium and magnesium in the S20 group were significantly higher than in the C and S40 groups. Although serum osteo calcin was not affected by the addition of sudachi juice, the urinary pyridinoline and deoxy pyridinoline concentrations in the S40 group were significantly lower than in the C and S20 groups. Our results indicate that sudachi juice added to shirasuboshi was associated with increased calcium bioavailability and suppressed bone resorption in rats.