Kawabata Kohei, Karahashi Minako, Sakamoto Takeshi, Tsuji Yukiho, Yamazaki Tohru, Okazaki Mari, Mitsumoto Atsushi, Kudo Naomi, Kawashima Yoichi
School of Pharmaceutical Sciences, Josai University.
Biol Pharm Bull. 2016;39(12):1995-2008. doi: 10.1248/bpb.b16-00470.
Different monounsaturated fatty acid (MUFA) species have distinct pathophysiological activities. cis-Palmitoleic acid (16:1n-7) was previously reported to improve insulin sensitivity in animal studies. The proportions of hepatic MUFAs are generally considered to reflect changes in the activities of fatty acid modifications (∆9 desaturation and fatty acid elongation). However, hepatic levels of 16:1n-7 are markedly lower than those of oleic acid (18:1n-9). Nevertheless, no convincing explanation has yet been provided for the low level of 16:1n-7. We hypothesized that fatty acid degradation plays a key role in maintaining a low 16:1n-7 proportion in the liver. In order to corroborate the link between β-oxidation and the proportion of 16:1n-7, rats were fed a control diet, fed a fat-free diet to up-regulate fatty acid modifications, but not β-oxidation, or treated with clofibric acid to up-regulate fatty acid modifications and β-oxidation. The nutritional manipulation markedly increased the proportions of 16:1n-7, 18:1n-9, and cis-vaccenic acid (18:1n-7). Although the pharmacological manipulation enhanced fatty acid modifications to largely the same extent as the nutritional manipulation and markedly elevated the proportion of 18:1n-9, those of 16:1n-7 and 18:1n-7 remained largely unchanged. The oxidation rates of 16:1n-7, 18:1n-9, and 18:1n-7 in liver slices were in the following order: 16:1n-7>18:1n-7≑18:1n-9 in control livers, and were increased by the pharmacological manipulation and decreased by the nutritional manipulation. These results strongly suggest that β-oxidation, in concert with fatty acid modifications, plays a key role in regulating the MUFA profile and is crucially involved in maintaining low 16:1n-7 levels in the liver.
不同的单不饱和脂肪酸（MUFA）种类具有不同的病理生理活性。在动物研究中，此前有报道称顺式棕榈油酸（16:1n-7）可改善胰岛素敏感性。肝脏中MUFA的比例通常被认为反映了脂肪酸修饰（Δ9去饱和和脂肪酸延长）活性的变化。然而，肝脏中16:1n-7的水平明显低于油酸（18:1n-9）。尽管如此，对于16:1n-7水平较低的情况，尚未有令人信服的解释。我们推测脂肪酸降解在维持肝脏中低比例的16:1n-7方面起关键作用。为了证实β-氧化与16:1n-7比例之间的联系，给大鼠喂食对照饮食、喂食无脂饮食以上调脂肪酸修饰但不上调β-氧化，或用氯贝酸处理以上调脂肪酸修饰和β-氧化。营养操作显著增加了16:1n-7、18:1n-9和顺式vaccenic酸（18:1n-7）的比例。尽管药物操作在很大程度上与营养操作一样增强了脂肪酸修饰，并显著提高了18:1n-9的比例，但16:1n-7和18:1n-7的比例基本保持不变。肝切片中16:1n-7、18:1n-9和18:1n-7的氧化速率顺序如下：对照肝脏中16:1n-7>18:1n-7≑18:1n-9，药物操作使其增加，营养操作使其降低。这些结果强烈表明，β-氧化与脂肪酸修饰协同作用，在调节MUFA谱中起关键作用，并且在维持肝脏中低水平的16:1n-7方面至关重要。
