Dietary scallop oil prepared from the internal organs of Japanese giant scallop (Patinopecten yessoensis) improved mite allergen-induced atopic dermatitis-like symptoms on the dorsal skin of NC/Nga mice.

This study aimed to investigate the effects of scallop oil (SCO) on atopic dermatitis (AD)-like symptoms induced by mite allergens in the dorsal and ear skins of NC/Nga mice compared to those of refined corn oil and krill oil (KO). SCO, rich in n-3 polyunsaturated fatty acids and phospholipids, was prepared from the internal organs of Japanese giant scallop, an underutilized fishery resource in Japan. Results showed that SCO intake improved AD-like symptoms, including ear edema, ear thickness, and transepidermal water loss of dorsal skin, and tended to decrease the scratching behavior, whereas KO intake did not. Further, SCO intake decreased the degranulated mast cell count and increased the tight junction protein claudin-1 expression, which is important for the barrier function, in the dorsal skin compared to refined corn oil intake. SCO improved the AD-like symptoms by suppressing mast cell degranulation and strengthening the barrier function of dorsal skin in NC/Nga mice.

Chronic Treatment with Metformin Has No Disrupting Effect on the Hepatic Circadian Clock in Mice.

Background and Objectives: The antidiabetic agent metformin is known to activate AMP-activated protein kinase (AMPK) in various tissues. Because AMPK can modulate intracellular circadian clocks through regulating the stability of clock components, a single dose of metformin has been reported to affect circadian clocks in the peripheral tissues. In this study, therefore, we investigated whether chronic treatment with metformin causes the impairment of circadian clocks, especially if given at an inappropriate time. Materials and Methods: Non-diabetic C57BL/6J mice were allowed access to food only during 4 h at the beginning of the dark period, and repeatedly i.p. injected with a nearly maximum non-toxic dose of metformin, once daily either at 4 h after the beginning of the dark period or at the beginning of the light period. Diabetic ob/ob mice were given free access to food and treated with metformin in drinking water. Results: Under the controlled feeding regimen, 8-day treatment with metformin did not alter the mRNA expression rhythms of clock genes in both liver and adipose tissue of C57BL/6J mice, regardless of dosing time. In addition, chronic treatment with metformin for 2 weeks affected hepatic AMPK activation rhythm but did not disrupt the circadian clocks in the liver and adipose tissues of the ob/ob mice. Conclusions: These results mitigate concerns that treatment with metformin impairs peripheral circadian clocks, although confirmation is needed in humans.

Gummi Formulations Comprising Amenamevir Solid Dispersions with Polyvinyl Alcohol.

The aim of the present study was to determine whether solid dispersions (SDs) are applicable to gummi formulations. Amenamevir was selected as a model of a poorly water-soluble drug, and polyvinyl alcohols (PVAs) with various degrees of hydrolysis (PVA 66, PVA 80, PVA 88, and PVA 66/88) were used as SD carriers. Design of experiments (DOE) was used to develop a gummi formulation that was suitable for an amenamevir SD using SD with PVA 66. Dissolution studies and clinical sensory tests on 11 formulations calculated by DOE revealed that a gummi formulation comprising 10.5% gelatin and 22.8% water was suitable for SD of the drug. Gummi formulations comprising amenamevir SDs with various PVAs were prepared using the determined gummi formulation, and their ability to dissolve amenamevir, their stability, and their oral absorption in dogs were evaluated. The results suggested that PVA 66, PVA 66/88, and PVA 80 were appropriate in terms of dissolution, stability, and in vivo absorption, respectively. Considering these results comprehensively, it was concluded that PVA 80, which enabled the highest degree of absorption, was the most suitable SD carrier for gummi formulations. Thus, it was possible to apply a PVA SD of amenamevir to gummi formulations.

Effects of Daily Consumption of Scallop Oil Prepared from Internal Organs of Japanese Giant Scallop (Patinopecten yessoensis) on Serum Lipid Composition and Its Safety: A Randomized, Double-blind, Placebo-controlled, Parallel Group Comparison Study.

Scallop oil (SCO) prepared from the internal organs of the Japanese giant scallop (Patinopecten yessoensis) contains eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and phospholipids (PL). It was previously shown that SCO consumption improves cholesterol and triacylglycerols (TG) contents in mice. The present study demonstrated the effects of daily SCO consumption (1.2 g/day, containing 376 mg of EPA, 63 mg of DHA, and 150 mg of PL) for 12 weeks in human subjects. In this randomized, doubleblind, placebo-controlled, parallel group comparison study, 70 Japanese subjects with serum TG levels ≥120 but < 200 mg/dL were recruited and randomly assigned to the SCO or placebo group. All subjects ingested six capsules per day for 12 weeks. We conducted medical interviews, body composition measurements, vital sign examinations, and blood sampling at weeks 0 (baseline), 4, 8, and 12, and measured peripheral blood flow at weeks 0 and 12. In the case of subjects with higher serum TG levels, SCO consumption decreased the changes in serum TG and malondialdehyde-low density lipoprotein (MDA-LDL) levels compared with the placebo group. Safety assessment revealed no medically significant changes due to continuous SCO consumption. The findings indicate that 1.2 g/day of SCO consumption may be beneficial for reducing serum TG and MDA-LDL levels in persons with higher TG levels.

Dietary Bamboo Charcoal Decreased Visceral Adipose Tissue Weight by Enhancing Fecal Lipid Excretions in Mice with High-Fat Diet-Induced Obesity.

Bamboo charcoal (BC) powder is prepared from thick bamboo stems via dry distillation and is often used for food coloring. Due to the unique structure of the micropores in bamboo stems, BC powder also serves as an indigestible carrier to prevent the absorption of toxic substances and nutrients from the digestive tract. This study evaluated the health-promoting function of BC, particularly its effects in decreasing visceral adipose tissue in a mouse model with high-fat diet (HFD)-induced obesity. Four-week-old male C57BL/6J mice were divided into three groups and fed either a low-fat (LF) diet (7% fat), HF diet (25% fat), or HF diet with 0.5% BC (HF-BC). After 80 days, the HF-BC diet was found to have decreased epididymal and mesenteric white adipose tissue weights compared to HFD. The inhibition of visceral fat accumulation by BC intake was partly due to enhanced fecal fatty acid excretion induced by its bile acid-binding and pancreatic lipase inhibition. Contrarily, the gut microbiota, known to influence systemic energy metabolism, did not change significantly between the HF and HF-BC groups. These results indicate that dietary BC inhibits visceral fat accumulation, which could reduce obesity development.

Dietary Phospholipids Prepared From Scallop Internal Organs Attenuate the Serum and Liver Cholesterol Contents by Enhancing the Expression of Cholesterol Hydroxylase in the Liver of Mice.

In this study, we successfully prepared scallop oil (SCO), which contains high levels of phospholipids (PL) and eicosapentaenoic acid (EPA), from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), one of the most important underutilized fishery resources in Japan. The intake of SCO lowers the serum and liver cholesterol contents in mice; however, whether the fatty acids (FA) composition or PL of SCO exhibits any cholesterol-lowering effect remains unknown. To elucidate whether the cholesterol-lowering function is due to FA composition or PL of SCO, and investigate the cholesterol-lowering mechanism by SCO, in the present study, mice were fed SCO's PL fraction (SCO-PL), triglyceride (TG)-type oil with almost the same FA composition as SCO-PL, called SCO's TG fraction (SCO-TG), soybean oil (SOY-TG), and soybean's PL fraction (SOY-PL). Male C57BL/6J mice (5-week-old) were fed high-fat and cholesterol diets containing 3% (w/w) experimental oils (SOY-TG, SOY-PL, SCO-TG, and SCO-PL) for 28 days. The SCO-PL diet significantly decreased the serum and liver cholesterol contents compared with the SOY-TG diet, but the intake of SOY-PL and SCO-TG did not show this effect. This result indicated that the serum and liver cholesterol-lowering effect observed in the SCO intake group was due to the effect of SCO-PL. The cholesterol-lowering effect of SCO-PL was in part related to the promotion of liver cholesterol 7α-hydroxylase (CYP7A1) expression, which is the rate-limiting enzyme for bile acid synthesis. In contrast, the expression levels of the ileum farnesoid X receptor (Fxr) and fibroblast growth factor 15 (Fgf15), which inhibit the expression of liver CYP7A1, were significantly reduced in the SCO-PL group than the SOY-TG group. From these results, the increase in the liver CYP7A1 expression by dietary SCO-PL was in part through the reduction of the ileum Fxr/Fgf15 regulatory pathway. Therefore, this study showed that SCO-PL may be a health-promoting component as it lowers the serum and liver cholesterol contents by increasing the liver CYP7A1 expression, which is not seen in SOY-PL and SCO-TG.

Comparison of the Cholesterol-Lowering Effect of Scallop Oil Prepared from the Internal Organs of the Japanese Giant Scallop (Patinopecten yessoensis), Fish Oil, and Krill Oil in Obese Type II Diabetic KK-A y Mice.

Due to the growing demand of n-3 polyunsaturated fatty acids (PUFA) as supplements and pharmaceutical products worldwide, there are concerns about the exhaustion of n-3 PUFA supply sources. We have successfully prepared high-quality scallop oil (SCO), containing high eicosapentaenoic acid and phospholipids contents, from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), which is the largest unutilized marine resource in Japan. This study compared the cholesterol-lowering effect of SCO with fish oil (menhaden oil, MO) and krill oil (KO) in obese type II diabetic KK-A y mice. Four-week-old male KK-A y mice were divided into four groups; the control group was fed the AIN93G-modified high-fat (3 wt% soybean oil + 17 wt% lard) diet, and the other three groups (SCO, MO, and KO groups) were fed a high-fat diet, in which 7 wt% of the lard in the control diet was replaced with SCO, MO, or KO, respectively. After the mice were fed the experimental diet for 42 days, their serum, liver, and fecal lipid contents as well as their liver mRNA expression levels were evaluated. The SCO group had significantly decreased cholesterol levels in the serum and liver; this decrease was not observed in the MO and KO groups. The cholesterol-lowering effect of SCO was partly mediated by the enhancement of fecal total sterol excretion and expression of liver cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis. These results indicate that dietary SCO exhibits serum and liver cholesterol-lowering effects that are not found in dietary MO and KO and can help prevent lifestyle-related diseases.

Dietary Eicosapentaenoic Acid and Docosahexaenoic Acid Ethyl Esters Influence the Gut Microbiota and Bacterial Metabolites in Rats.

Dietary fish oil containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to affect the diversity and composition of gut microbiota and bacterial metabolites. However, few reports have focused on the effects of EPA and DHA on gut microbiota diversity and bacterial metabolites. This study evaluated the effects of dietary EPA-ethyl ester (EE) and DHA-EE on steroid metabolism, gut microbiota, and bacterial metabolites in Wistar rats. Male rats were fed the experimental diets containing 5% (w/w) soybean oil-EE (SOY diet), EPA-EE (EPA diet), and DHA-EE (DHA diet) for four weeks. The lipid contents in the serum and liver, mRNA expression levels in the liver, and the diversity, composition, and metabolites of the gut microbiota were evaluated. The EPA and DHA diets decreased serum and liver cholesterol contents compared to the SOY diet. In addition, there were no significant changes in gene expression levels related to steroid metabolism in the liver between the EPA and DHA groups. Rats fed the DHA diet had lower microbiota diversity indices, such as Simpson and Shannon indices, than rats fed the SOY and EPA diets. In addition, rats fed EPA and DHA had significant differences in the relative abundance of microbiota at the genus level, such as Phascolarctobacterium, Turicibacter, and [Eubacterium]. Therefore, it was concluded that EPA and DHA have different effects on the diversity and composition of gut microbiota under the experimental conditions employed herein.

Effects of dietary oils prepared from the internal organs of the Japanese giant scallop (Patinopecten yessoensis) on cholesterol metabolism in obese type-II diabetic KK-Ay mice.

Our research team has successfully prepared high-quality scallop oil (SCO), containing high eicosapentaenoic acid (EPA) and phospholipids (PL) from the internal organs of Japanese giant scallop (Patinopecten yessoensis) which is the largest unutilized marine resource in Japan. In this study, we prepared SCOs from scallop internal organs obtained from Mutsu (Aomori) and Uchiura (Hokkaido) bays in Japan, and named them SCO-M and SCO-U, respectively. This study aimed to investigate the effects of dietary SCO-M and SCO-U on cholesterol metabolism in obese type-II diabetic KK-Ay mice. Four-week-old male KK-Ay mice were divided into four groups. The Control group was fed with AIN93G-modified high-fat (3 wt% soybean oil + 17 wt% lard) diet, and the other groups were fed with high-fat diet, in which 7 wt% of the lard contained in the Control diet was replaced with SCO-M, SCO-U, or tuna oil (TO). After the mice had been fed with the experimental diet for 49 days, their serum, liver, and fecal lipid contents, as well as their liver messenger ribonucleic acid expression levels, were evaluated. The SCO-M and SCO-U groups were significantly decreased liver cholesterol contents compared to those of the Control and TO groups, partially through the enhancement of the fecal neutral sterol excretions and the tendency to increase the cholesterol 7α-hydroxylase expression level of the liver. These results indicated that dietary SCO-M and SCO-U exhibited cholesterol-lowering functions in the liver that can help prevent the development of lifestyle-related diseases.

Single and Repeated Dose 28-Day and 13-Week Toxicity Studies of Oil Prepared from the Internal Organs of the Japanese Giant Scallop (Patinopecten yessoensis) in Mice.

Internal organs of discarded scallops are rich in omega-3 polyunsaturated fatty acids, but it is not used as a food ingredient due to the presence of toxic substances. Recently, our research team prepared high-quality scallop oil (SCO) from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), in which cadmium and diarrhetic shellfish toxin are below regulated levels. In this study, SCO was prepared from the internal organs of scallops obtained from Mutsu and Uchiura bays in Japan, and was referred to as SCO-M (scallop oil from Mutsu bay) and SCO-U (scallop oil from Uchiura bay), respectively. Acute and subacute toxicity studies were performed to assess the safety of the prepared SCO. In acute toxicity study, mice were orally administered SCO-M and SCO-U at a single dose of 5,000 mg/kg body weight. In a 28-day repeated oral dose toxicity study, the mice were fed diets containing 1% and 5% SCO-M and SCO-U; and in a 13-week repeated oral dose toxicity study, the mice were fed 5% SCO-M and SCO-U. There were no toxicologically significant changes in clinical signs, hematology, blood chemistry, and organ weights at any dose during the experiment. Therefore, it was concluded that SCO-M and SCO-U are safe for use as food ingredients under the experimental conditions of this study.

Dietary Fat Influences the Expression of Genes Related to Sterol Metabolism and the Composition of Cecal Microbiota and Its Metabolites in Rats.

Numerous studies have evaluated the composition of gut microbiota in experimental animals fed high-fat or low-fiber diets. However, few reports have focused on the effects of different fatty acid (FA) compositions on the diversity of gut microbiota and its metabolites. Therefore, the aim of this research was to investigate the effects of different dietary fats on liver mRNA expression levels of genes related to cholesterol and bile acid (BA) metabolism, as well as to investigate cecal microbiota composition and bacterial metabolites composition in rats. Four-week-old male Wistar/ST rats were fed a 15% fat diet for 30 days, including from different sources (soybean oil, lard, menhaden oil, or tuna oil). Then, the rats' cecal microbiota composition was determined by sequencing the 16S ribosomal RNA gene using next-generation sequencing. Lard diet drastically decreased the expression level of liver ATP-binding cassette subfamily G genes (Abcg5 and Abcg8 genes) compared with other diets. Menhaden oil diet increased the fecal BA excretion compared with soybean oil and lard diets. Fecal BA excretion tended to be positively correlated with the relative abundance of Firmicutes, and negatively correlated with the relative abundance of Bacteroidetes. These results have shown that dietary fats with different FA compositions have a different effect on the relative composition of cecal microbiota, and in particular, menhaden oil may have very different effects compared to other experimental fats. The effects of fish oils on the cecal microbiota may differ greatly depending on the ratio of EPA to DHA and the composition of FA other than n-3 polyunsaturated FA. Our results provided new insights on the way different dietary fat sources affect sterol metabolism and alter cecal microbiota composition in rats.