Kouichi Yabiku

Brown Rice and Its Component, γ-Oryzanol, Attenuate the Preference for High-Fat Diet by Decreasing Hypothalamic Endoplasmic Reticulum Stress in Mice

Brown rice is known to improve glucose intolerance and prevent the onset of diabetes. However, the underlying mechanisms remain obscure. In the current study, we investigated the effect of brown rice and its major component, γ-oryzanol (Orz), on feeding behavior and fuel homeostasis in mice. When mice were allowed free access to a brown rice–containing chow diet (CD) and a high-fat diet (HFD), they significantly preferred CD to HFD. To reduce hypothalamic endoplasmic reticulum (ER) stress on an HFD, mice were administered with 4-phenylbutyric acid, a chemical chaperone, which caused them to prefer the CD. Notably, oral administration of Orz, a mixture of major bioactive components in brown rice, also improved glucose intolerance and attenuated hypothalamic ER stress in mice fed the HFD. In murine primary neuronal cells, Orz attenuated the tunicamycin-induced ER stress. In luciferase reporter assays in human embryonic kidney 293 cells, Orz suppressed the activation of ER stress–responsive cis-acting elements and unfolded protein response element, suggesting that Orz acts as a chemical chaperone in viable cells. Collectively, the current study is the first demonstration that brown rice and Orz improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice fed an HFD.

Natural food science based novel approach toward prevention and treatment of obesity and type 2 diabetes: recent studies on brown rice and γ-oryzanol.

The prevalences of obesity and type 2 diabetes mellitus are dramatically increasing, and there is a strong need for more effective and safer therapies. However, some of drugs show limited efficacy and considerable adverse effects. Furthermore, artificial energy-dense foods and non-caloric foods may promote overeating and weight gain. In this context, a natural food-based approach may represent a valuable means of tackling the obesity-diabetes syndrome. Although recent studies have shown that brown rice improves glucose intolerance and prevents obesity and type 2 diabetes in humans, the underlying molecular mechanisms remain unclear. We found that one of the major components of brown rice, γ-oryzanol (Orz), plays an important role in the metabolically beneficial effects of brown rice. Orz acts as a chemical chaperone and decreases high fat diet (HFD)-induced endoplasmic reticulum (ER) stress in the hypothalamus, thereby leading to a significant shift in preference from fatty to healthy foods. Orz also decreases HFD-induced ER stress in pancreatic β-cells and improves β-cell function. Notably, Orz directly acts on pancreatic islets and enhances glucose-stimulated insulin secretion (GSIS). This evidence highlights food preference as a promising therapeutic target in obesity-diabetes syndrome and suggests that brown rice and Orz may have potential for the treatment of obesity and type 2 diabetes in humans.

Cytotoxic T-Lymphocyte Antigen-4 Gene Polymorphisms and Human T-Cell Lymphotrophic Virus-1 Infection: Their Associations with Hashimoto's Thyroiditis in Japanese Patients

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) decreases the immune response of T cells by inactivating the signal that occurs with interaction between CD28 on T cells and B7 on antigen-presenting cells. Gene polymorphisms involving CTLA-4 promoter (-318 C/T), exon 1 (49 A/G), and exon 4 (microsatellite (AT)n) have been linked to Hashimotos thyroiditis (HT) and other autoimmune diseases. HT also has a reported association with human T-cell lymphotrophic virus-1 (HTLV-1) infection. We investigated the occurrence of CTLA-4 polymorphisms in Japanese patients with HT with and without anti-HTLV-1 antibodies (HTLV-1 Ab). DNA samples from 143 patients with HT and 199 controls were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzymes, Bbv 1, Tse 1, and Mse 1. In the HTLV-1 Ab-positive group the exon 1 G allele was more frequent in patients with HT than in controls (67% vs. 53%, p = 0.0377), and in HTLV-1 Ab-negative group it was also frequent in patients with HT than in controls (68% vs. 53%, p = 0.0041). Frequency of the G allele in HT with HTLV-1 Ab was comparable to those without HTLV-1 Ab. Frequency of polymorphism in the promoter did not differ between patients with HT and controls, nor between controls with and without HTLV-1 Ab. HTLV-1 infection is not associated with CTLA-4 polymorphisms in either HT or controls. HTLV-1 infection is not regulated by genetic factor such as CTLA-4, and may affect occurrence of HT as an independent purely environmental factor.