Dietary supplementation of deoxyribonucleic acid derived from chum salmon milt improves liver function in healthy Japanese individuals: a placebo-controlled, randomised, double-blind, parallel-group clinical trial.

A placebo-controlled, randomised, double-blind, parallel-group comparative study was conducted to investigate the effect of continuous intake of salmon milt (SM) DNA for 12 weeks on the improvement of liver function in 50 healthy Japanese participants aged 30 to 70 years with alanine aminotransferase (ALT) levels of 25-87 U L-1 in men, 22-66 U L-1 in women, of BMI 22.1-29.4 kg m-2. Comparative analysis of hepatic functions and several other parameters, including anthropometric parameters in placebo and SM DNA administered groups, revealed no significant differences in serum ALT level. SM DNA significantly improved the liver-to-spleen (L/S) ratio, body weight, and BMI in the main group. In addition to these parameters, in the BMI < 25 kg m-2 subgroup, the leptin level was significantly reduced. No adverse reactions or abnormal changes, symptoms, or findings in the clinical examination after intake of the test food containing SM DNA were observed. Furthermore, no significant difference in uric acid levels between SM DNA and placebo groups indicated the safety of using SM DNA as a food supplement. These results demonstrated the potential fatty liver improvement and anti-obesity action of continuous intake of SM DNA for 12 weeks without any significant adverse effects.

Evaluation of the efficacy and safety of chum salmon milt deoxyribonucleic acid for improvement of hepatic functions: a placebo-controlled, randomised, double-blind, and parallel-group, pilot clinical trial.

The increased prevalence of nonalcoholic fatty liver disease (NAFLD) is a critical public health concern. Deoxyribonucleic acid (DNA) from chum salmon (Oncorhynchus keta) milt (salmon milt DNA; SM DNA), a by-product obtained during industrial processing of the pharmaceutical raw material protamine, ameliorates hepatosteatosis in animals. This randomised, double-blind, parallel-group comparative study evaluated the effects of SM DNA on hepatic function in healthy Japanese participants with slightly decreased liver function and high alanine aminotransferase level and body mass index. Fifty participants were included in the study. The participants were divided into the placebo (n = 24) and SM DNA (n = 26) groups and administered equal doses of placebo (dextrin) and SM DNA (530 mg day-1), respectively. No significant alleviating effects of SM DNA were observed on the primary (hepatic functions and liver-to-spleen ratio), and secondary (NAFLD fibrosis score, serum protein levels, blood glucose, blood lipids, inflammatory markers, adipokines, cytokines, fatigue scoring, and skin conditions) endpoints. Subsequently, a sex-based subgroup analysis revealed a significant improvement in the primary and secondary outcomes in males ingesting SM DNA compared with those in males who were administered placebo. However, no such effect was observed in females. Overall, this clinical study demonstrated the anti-obesity potential of SM DNA and suggested that SM DNA can benefit hepatic function in males.

Effect of one-week administration of dipeptidyl peptidase-IV inhibitory peptides from chum salmon milt on postprandial blood glucose level: a randomised, placebo-controlled, double-blind, crossover, pilot clinical trial.

Salmon milt peptide (SMP), an unused fish processing byproduct, exhibits strong inhibitory activity against dipeptidyl peptidase-IV (DPP-IV) and a suppressive effect on postprandial hyperglycaemia in Sprague-Dawley rats. Herein, we conducted a randomised, placebo-controlled, double-blind, crossover study of healthy Japanese subjects to investigate the effect of glucose loading on postprandial blood glucose levels after one week of administering continuous or single dose of 500 mg of SMP. The primary and secondary outcomes of reduced blood glucose and insulin levels were not met in the 14 subjects included in the analysis. This may be due to the ineffectiveness of SMP in insulin resistance due to its DPP-IV inhibitory activity. Therefore, we conducted a SMP subgroup analysis based on the homeostasis model assessment of insulin resistance (HOMA-IR); the group with normal HOMA-IR (<1.6) had a significantly lower area under the curve and blood glucose at 60 min after glucose loading than the group with HOMA-IR ≥1.6. These results suggest that SMP is effective in subjects without insulin resistance. There were no adverse events associated with the test food, and SMP was considered safe. This report is the first to investigate the effect of a food ingredient with DPP-IV inhibitory activity in a clinical trial.

Maternal fish oil supplementation ameliorates maternal high-fructose diet-induced dyslipidemia in neonatal mice with suppression of lipogenic gene expression in livers of postpartum mice.

Maternal fructose consumption during pregnancy and lactation is associated with metabolic dysregulation in offspring. We tested the hypothesis that fish oil (FO) supplementation during pregnancy and lactation improves fructose-induced metabolic dysregulation in postpartum dams and offspring mice. We therefore aimed to determine the effects of FO supplementation on metabolic disruption in neonatal mice and dams induced by a maternal high-fructose diet (HFrD). The weight of the offspring of dams fed with HFrD on postnatal day 5 was significantly low, but this was reversed by adding FO to the maternal diet. Feeding dams with HFrD significantly increased plasma concentrations of triglycerides, uric acid, and total cholesterol, and decreased free fatty acid concentrations in offspring. Maternal supplementation with FO significantly suppressed HFrD-induced hypertriglyceridemia and hyperuricemia in the offspring. Maternal HFrD induced remarkable mRNA expression of the lipogenic genes Srebf1, Fasn, Acc1, Scd1, and Acly in the postpartum mouse liver without affecting hepatic and plasma lipid levels. Although expression levels of lipogenic genes were higher in the livers of postpartum dams than in those of nonmated mice, HFrD feeding increased the hepatic lipid accumulation in nonmated mice but not in postpartum dams. These findings suggest that although hepatic lipogenic activity is higher in postpartum dams than nonmated mice, the lipid consumption is enhanced in postpartum dams during pregnancy and lactation. Maternal FO supplementation obviously suppressed the expression of these lipogenic genes. These findings coincide with reduced plasma triglyceride concentrations in the offspring. Therefore, dietary FO apparently ameliorated maternal HFrD-induced dyslipidemia in offspring by suppressing maternal lipogenic gene expression and/or neonatal plasma levels of uric acid.

Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding.

Chrononutrition is the science of nutrition based on chronobiology. Numerous epidemiological studies have shown that fish oil (FO) reduces the risk of cardiovascular events through various actions such as lowering triglycerides. The present study aimed to determine the time of day when the hypertriglyceridemia-decreasing ability of FO is optimal in mice. A high-fructose diet (HFrD) that induces hyperlipidemia in mice was replaced with the same diet containing 4% FO (HFrD-4% FO) at different times of the day for 2 weeks as described below. Mice were fed with HFrD alone (CTRL) or with HFrD containing 4% FO for 12 h around the time of activity onset [breakfast (BF)-FO] or offset [dinner (DN)-FO]. Plasma and liver concentrations of triglycerides and total cholesterol were reduced in BF-FO but not in DN-FO mice compared with CTRL mice. The temporal expression of genes associated with fatty acid synthesis such as Fasn, Acaca, Scd1 and Acly in the liver was significantly suppressed in both BF-FO and DN-FO mice. Expression levels of Scd1 in epididymal adipose tissue were significantly suppressed only in the BF-FO mice. Plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid were far more increased in BF-FO than in DN-FO mice. Significantly more of these n-3 polyunsaturated fatty acids (PUFAs) were excreted in the feces of DN-FO than of BF-FO mice. These findings suggest that dietary FO exerts more hypolipidemic activity at the time of breakfast than dinner because the intestinal absorption of n-3 PUFAs is more effective at that time.

Mammalian copper chaperone Cox17p has an essential role in activation of cytochrome C oxidase and embryonic development.

Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO) and for delivery of copper ions to the mitochondrion for insertion into the enzyme in yeast. Although this small protein has already been cloned or purified from humans, mice, and pigs, the function of Cox17p in the mammalian system has not yet been elucidated. In vitro biochemical data for mammalian Cox17p indicate that the copper binds to the sequence -KPCCAC-. Although mouse embryos homozygous for COX17 disruption die between embryonic days E8.5 and E10, they develop normally until E6.5. This phenotype is strikingly similar to embryos of Ctr1(-/-), a cell surface copper transporter, in its lethality around the time of gastrulation. COX17-deficient embryos exhibit severe reductions in CCO activity at E6.5. Succinate dehydrogenase activity and immunoreactivities for anti-COX subunit antibodies were normal in the COX17(-/-) embryos, indicating that this defect was not caused by the deficiency of other complexes and/or subunits but was caused by impaired CCO activation by Cox17p. Since other copper chaperone (Atox1 and CCS)-deficient mice show a more moderate defect, the disruption of the COX17 locus causes the expression of only the phenotype of Ctr1(-/-). We found that the activity of lactate dehydrogenase was also normal in E6.5 embryos, implying that the activation of CCO by Cox17p may not be essential to the progress of embryogenesis before gastrulation.