Oishi Katsutaka, Yamamoto Saori, Itoh Nanako, Nakao Reiko, Yasumoto Yuki, Tanaka Keiko, Kikuchi Yosuke, Fukudome Shin-ichi, Okita Kimiko, Takano-Ishikawa Yuko
Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan; Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan;
Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan;
J Nutr. 2015 Feb;145(2):199-206. doi: 10.3945/jn.114.202754. Epub 2014 Nov 26.
Epidemiologic studies have shown that the consumption of whole grains can reduce the risk of type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality. However, the underlying mechanisms remain a matter of debate.
We aimed to determine the effects of wheat bran-derived alkylresorcinols on diet-induced metabolic disorders in mice.
We fed C57BL/6J mice a normal refined diet or a high-fat, high-sucrose diet [29.1% fat, 20.7% protein, 34.0% carbohydrates containing 20.0% sucrose (w/w)] alone (FS) or containing 0.4% (wt:wt) alkylresorcinols (FS-AR) for 10 wk.
The alkylresorcinols suppressed FS-induced increases in body weight by 31.0% as well as FS-induced hepatic triglyceride accumulation (means ± SEMs: 29.6 ± 3.18 and 19.8 ± 2.42 mg/g tissue in the FS and FS-AR groups, respectively), without affecting energy intake. We measured circadian changes in blood metabolic hormones and found that FS-induced hyperinsulinemia (5.1 and 2.1 μg/L at night in the FS and FS-AR groups, respectively) and hyperleptinemia (21.6 and 10.8 μg/L at night in the FS and FS-AR groups, respectively) were suppressed by alkylresorcinols. Glucose and insulin tolerance tests showed that alkylresorcinols significantly reduced fasting blood glucose concentrations (190 ± 3.62 and 160 ± 8.98 mg/dL in the FS and FS-AR groups, respectively) and suppressed glucose intolerance as well as insulin resistance induced by the FS diet. Furthermore, alkylresorcinols significantly increased insulin-stimulated hepatic serine/threonine protein kinase B phosphorylation compared to the FS diet (+81.3% and +57.4% for Ser473 and Thr308, respectively). On the other hand, pyruvate and starch tolerance tests suggested that alkylresorcinols did not affect gluconeogenesis and carbohydrate digestion, respectively. Alkylresorcinols significantly increased fecal cholesterol excretion by 39.6% and reduced blood cholesterol concentrations by 30.4%, while upregulating the expression of hepatic cholesterol synthetic genes such as sterol regulatory element binding protein 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1).
These findings suggest that wheat alkylresorcinols increase glucose tolerance and insulin sensitivity by suppressing hepatic lipid accumulation and intestinal cholesterol absorption, which subsequently suppresses diet-induced obesity in mice.
流行病学研究表明，食用全谷物可降低2型糖尿病、心血管疾病和全因死亡率的风险。然而，其潜在机制仍存在争议。
我们旨在确定麦麸衍生的烷基间苯二酚对小鼠饮食诱导的代谢紊乱的影响。
我们给C57BL/6J小鼠喂食正常精制饮食或高脂肪、高蔗糖饮食[29.1%脂肪，20.7%蛋白质，34.0%碳水化合物，含20.0%蔗糖（重量/重量）]，单独喂食（FS）或含0.4%（重量/重量）烷基间苯二酚（FS-AR），持续10周。
烷基间苯二酚使FS诱导的体重增加抑制了31.0%，同时也抑制了FS诱导的肝脏甘油三酯积累（FS组和FS-AR组的均值±标准误分别为29.6±3.18和19.8±2.42mg/g组织），且不影响能量摄入。我们测量了血液代谢激素的昼夜变化，发现FS诱导的高胰岛素血症（FS组和FS-AR组夜间分别为5.1和2.1μg/L）和高瘦素血症（FS组和FS-AR组夜间分别为21.6和10.8μg/L）被烷基间苯二酚抑制。葡萄糖和胰岛素耐量试验表明，烷基间苯二酚显著降低空腹血糖浓度（FS组和FS-AR组分别为190±3.62和160±8.98mg/dL），并抑制了FS饮食诱导的葡萄糖不耐受和胰岛素抵抗。此外，与FS饮食相比，烷基间苯二酚显著增加胰岛素刺激的肝脏丝氨酸/苏氨酸蛋白激酶B磷酸化（Ser473和Thr308分别增加81.3%和57.4%）。另一方面，丙酮酸和淀粉耐量试验表明，烷基间苯二酚分别不影响糖异生和碳水化合物消化。烷基间苯二酚显著增加粪便胆固醇排泄39.6%，降低血液胆固醇浓度30.4%，同时上调肝脏胆固醇合成基因如固醇调节元件结合蛋白2（Srebf2）和3-羟基-3-甲基戊二酰辅酶A合酶1（Hmgcs1）的表达。
这些发现表明，小麦烷基间苯二酚通过抑制肝脏脂质积累和肠道胆固醇吸收来提高葡萄糖耐量和胰岛素敏感性，进而抑制小鼠饮食诱导的肥胖。
