Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia

Kazuyuki Ohara, Yuka Kiyotani, Asako Uchida, Reiko Nagasaka, Hiroyuki Maehara, Shigeharu Kanemoto, Masatoshi Hori, Hideki Ushio


Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102h, respectively), significantly different from the control values (p<0.01 and 0.05, respectively). γ-Aminobutyric acid (GABA) and abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102h, respectively) and was effective in an earlier phase from 30 to 54h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress.


γ-Oryzanol is a mixture of sterol esters of ferulic acid, found in rice-bran oil (Rogers et al., 1993).

The highest concentration of γ-oryzanol was recently extracted from the rice bran during the shorter milling duration (Rohrer and Siebenmorgen, 2004). Studies showed it lowered blood cholesterol in rats and that the addition of 0.5 percent γ-oryzanol to a cholesterolenriched diet effectively reduced triacylglycerols, LDL cholesterol, and VLDL cholesterol in the serum, and cholesterol in the liver (Nicolosi et al., 1993; Seetharamaiah and Chandrasekhara, 1993). In addition, γ-oryzanol was also an effective antioxidant, protecting ricebran oil from oxidation by iron or UV radiation (Jariwalla et al., 2001). Of the three major γ-oryzanol derivatives in rice bran, 24-methylenecycloartanyl ferulate exhibited the highest antioxidant activity compared to cycloartanyl ferulate or campestryl ferulate.

All three compounds were much stronger antioxidants than any of the vitamin E isomers (Xu et al., 2001). Earlier in vitro tests showed γ-oryzanol had superoxide dismutase-like antioxidant activity (Kim et al., 1995). A review by Cicero and Gaddi (2001) discusses some of the health claims made for γ-oryzanol, as well as the pharmacology and toxicology of rice-bran oil. Three major γ-oryzanol derivatives in oats. (From Xu et al., 2001. With permission.)

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Nicolosi, R.J., Rogers, E.J., Ausman, L.M., and Ormoefer, F.T., Rice bran oil and its health effects, in Rice Science and Technology, Marshall, W.E. and Wadsworth, J.I., Eds., Marcel Dekker, New York, 1993, pp. 421–437.

Rogers, E.J., Rice, S.M., Nicolosi, R.J., Carpenter, D.R., McClelland, C.A., and Romanczyk, L.R., Identification and quantitation of gamma-oryzanol components and simultaneous assessment of tocols in rice oil bran, J. Am. Oil Chem. Soc., 70:301–307, 1993.

Rohrer, C.A. and Siebenmorgen, T.J., Nutraceutical concentrations within the bran of various rice kernel thickness fractions, Biosyst. Eng., 88:453–460, 2004.

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Xu, Z., Hua, N., and Godber, J.S., Antioxidant activity of tocopherols, tocotrienols, and γ-oryzanol components from rice bran against cholesterol oxidation accelerated by 2,2′-azobis(2-methylpropionamide) dihydrochloride, J. Agric. Food Chem., 49:2077–2081, 2001.

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