JP7162289B2 - Vitamin A metabolism enhancer - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act ISSAAS 2017 International Conference/General Assembly Abstracts October 14, 2017

TECHNICAL FIELD The present invention relates to a vitamin A metabolism-promoting agent that enhances the metabolism of vitamin A in the liver.

Obesity due to westernization and lack of exercise not only causes dyslipidemia, hypertension, and type 2 diabetes, but obesity causes non-alcoholic fatty liver disease (NAFLD), which affects 10-30% of Japanese people. It is known that non-alcoholic steatohepatitis (NASH) progresses to liver cancer. Lifestyle-related diseases are a general term for diseases such as diabetes, dyslipidemia, hypertension, and hyperuricemia, which are thought to be deeply related to the onset of lifestyle-related diseases. It is said that this condition increases the risk of cancer, cerebrovascular disease, and heart disease, which are the three major causes of death, so urgent measures are required.

In particular, hepatic dysfunction is a factor that causes disorders in various functions such as metabolic function, detoxification, energy storage, and bile production. ing.

For example, Japanese Patent Application Laid-Open No. 2009-221193 describes a new use of rice-derived peptides by a method comprising the steps of treating sake lees with cellulase and β-amylase and then with protease N Amano G and Sumizyme AP. A hepatic dysfunction inhibitor consisting of a peptide mixture obtained by a method including a step of treating a peptide mixture or sake lees obtained by treating with cellulase and β-amylase and then treating with samoase is disclosed (Patent Document 1).

JP 2009-221193 A

Dyslipidemia is known to be caused by vitamin A deficiency. Therefore, if vitamin A metabolism in the liver can be improved, it is expected that various diseases caused by abnormal vitamin A metabolism will be improved.

Accordingly, an object of the present invention is to provide a vitamin A metabolism-promoting agent that improves vitamin A metabolism in the liver.

As a result of intensive studies to solve the above problems, the present inventors found that ingestion of pregelatinized brown rice promotes vitamin A metabolism and improves lipid metabolism disorders, and completed the present invention. rice field.

The present invention has been made based on such findings, and provides a vitamin A metabolism promoting agent characterized by containing pregelatinized brown rice as an active ingredient.

According to the present invention, vitamin A metabolism in the liver is enhanced by ingesting a vitamin A metabolism-promoting agent. It can be applied to the prevention, improvement, treatment, etc. of metabolic disorders, etc.

FIG. 3 shows the results of measuring the hepatic αSMA gene expression level in rats fed with pregelatinized brown rice. FIG. 2 shows the results of measuring liver retinyl palmitate concentration (a) and LRAT gene expression level (b) in rats fed with pregelatinized brown rice. FIG. 2 shows the results of measuring the Raldh1 gene expression level (a) and the RARβ gene expression level (b) in rats ingesting pregelatinized brown rice. FIG. 4 is a diagram for explaining CPT1 and MTP effects on β-oxidation and steatosis.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments according to the present invention will be described in detail. In the present embodiment, “brown rice” refers to rice from which the outer husk has been removed, and consists of bran (pericarp, seed coat, aleurone layer), endosperm (polished rice) and germ. . The variety and type of rice are not particularly limited, and non-glutinous rice, glutinous rice, germinated brown rice, germinated rice, split and pounded rice, black rice, red rice, and blended rice obtained by blending two or more of these can be used.

In this embodiment, pregelatinized brown rice is used as the brown rice. The method of pregelatinization is not particularly limited, and those used in normal cooking of brown rice can be used, examples of which include direct heat heating and steam heating. The heat treatment conditions may be any conditions as long as the brown rice is uniformly cooked (pregelatinized), and the temperature is 90 to 135° C. (preferably 98 to 125° C.) for 10 to 60 minutes (preferably 20 to 50 minutes). Although preferred, this range is not limiting.

In the present embodiment, the brown rice may be brown rice that maintains its shape, but it may also be a pulverized product such as coarsely pulverized brown rice or finely pulverized brown rice, a mixture of brown rice and pulverized products, or a mixture of various pulverized products. It's okay.

The vitamin A metabolism-promoting agent according to this embodiment can be formulated using a known formulation method, particularly a formulation technique suitable for oral intake. Formulations include coated tablets, capsules, granules, fine granules, powders, emulsions, syrups and the like.

The vitamin A metabolism promoting agent of the present embodiment can be blended with various food raw materials or additives as long as the object of the present invention is not impaired. Preferred food ingredients or additives include, for example, β-carotene, which is a precursor of vitamin A, oil that promotes the absorption of vitamin A, and polished rice (polished rice has some effect and is easier to eat than brown rice alone). etc. can be mentioned.

1. Materials and methods
Six-week-old male Zucker fatty rats and wild-type male Zucker Lean rats were preliminarily bred in AIN93G for 4 days, then divided into four experimental groups: Lean group, control group, WR (white rice), and BR (brown rice). They were bred for 10 weeks (Table 1). The basic feed composition was AIN93G for the Lean group and the control group, and AIN93G for the WR or BR. % by weight) was adjusted. Both pregelatinized white rice and pregelatinized brown rice supplied by Alpha Foods Co., Ltd. are used, and they are ground to a particle size of 150 μm or less (100 mesh pass) with a jet grinder (Seishin Kogyo Co., Ltd.). was used as feed. The Zucker fatty rat is an obesity model animal that develops NAFLD, and AIN-93G is the standard purification for nutritional research for mice and rats published by the American Institute of Nutrition in 1993. feed composition.

Retinyl palmitate, a vitamin A metabolite, was measured by HPLC (manufactured by Shimadzu Corporation, model CTO-10ASVP). HPLC conditions were as follows: column: Wakosil II 5C18AR; 4.6 mm × 250 mm, Mightysil RP-18GP II 150-4.6, flow rate 0.8 ml/min, solvent ethanol:water = 95:5, detection by fluorescence excitation wavelength (325 nm) absorption. wavelength (470 nm). Hepatic αSMA, LRAT, vitamin A metabolizing enzyme Raldh1, retinoic acid receptor β (RARβ), nuclear receptor PPARα of β-oxidation-related factors, mitochondrial β-oxidation rate-limiting enzyme CPT1a and insulin response factor The gene expression level of MTP was analyzed by real-time PCR (manufactured by Applied Biotechnology, format StepOne).

2. Results FIG. 1 shows the results of measuring the hepatic αSMA gene expression level in rats ingesting pregelatinized brown rice. Hepatic αSMA gene expression in BR was significantly decreased compared to the control group (p<0.05).

FIG. 2 is a diagram showing the results of measuring liver retinyl palmitate concentration (a) and LRAT (b) in rats ingesting pregelatinized brown rice, and FIG. 3 shows Raldh1 gene expression level (a) and RARβ gene It is a figure which shows the result of having measured the expression level (b).

As shown in FIGS. 2 and 3, liver retinyl palmitate concentration and Raldh1 and RARβ gene expression were significantly increased compared to the control group (p<0.05). In addition, the results shown in FIGS. 1 to 3 revealed that the intake of pregelatinized brown rice accelerated the metabolism of vitamin A.

FIG. 4 is a diagram to explain the effects of CPT1 and MTP on β-oxidation and steatosis. It has been reported that agonists of RARβ2, which is the receptor for retinoic acid, the active substance of vitamin A, activate PPARα, which in turn reduces NAFLD by activating fatty acid β-oxidation. The RARβ gene expression level, which correlates with the amount of retinoic acid, is significantly increased by ingestion of brown rice compared to the control group (Fig. 2b). In other words, pregelatinized brown rice intake increases vitamin A metabolism, especially RARβ, whose expression is controlled by retinoic acid levels, and increases the expression levels of β-oxidation-related genes such as PPARα and CPT1a, which are involved in improving fatty liver. A possibility was suggested (Fig. 4a,b). In addition, brown rice intake increases the expression level of the MTP gene, promotes the release of triglycerides (TG) into the blood as very low density lipoproteins (VLDL), and is thought to improve NAFLD ( Figure 4c).

From the above results, it was found that a vitamin A metabolism-improving agent containing pregelatinized brown rice as an active ingredient can improve vitamin A storage in the liver, thereby improving hepatic lipid metabolism associated with obesity.

Claims (2)

A vitamin A metabolism promoting agent characterized by containing pregelatinized brown rice as an active ingredient. The vitamin A metabolism enhancer according to claim 1, wherein the brown rice is a pulverized product.

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