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.