Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Diabetes. 2013 Jun;62(6):1945-56. doi: 10.2337/db12-0828. Epub 2013 Jan 24.
Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration, including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation and could result from a lack of local specialized proresolving lipid mediators (SPMs), such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3-derived SPMs in adipose tissue and the effects of dietary EPA/DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated the effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 (PD1) levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3-derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression, and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors, including 17-HDHA and PD1, contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications.
肥胖引起的慢性低度炎症源于脂肪组织，对肥胖引起的代谢恶化至关重要，包括胰岛素抵抗和 2 型糖尿病。慢性炎症可能是炎症未能积极消退的结果，也可能是由于缺乏局部特异性的促解决脂质介质（SPM），如 resolvins 和 protectins，它们来源于 n-3 多不饱和脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）。我们评估了肥胖诱导的脂肪组织中 n-3 衍生 SPM 的变化以及饮食 EPA/DHA 对其的影响。此外，我们用 SPM 前体治疗肥胖小鼠，研究其对炎症和代谢失调的影响。肥胖显著降低了鼠类脂肪组织中 DHA 衍生的 17-羟基二十二碳六烯酸（17-HDHA，resolvin D1 前体）和保护素 D1（PD1）水平。饮食 EPA/DHA 治疗在肥胖时恢复了 n-3 衍生脂质介质的内源性生物合成，同时减轻了脂肪组织炎症并改善了胰岛素敏感性。值得注意的是，17-HDHA 治疗降低了肥胖小鼠脂肪组织中炎症细胞因子的表达，增加了脂联素的表达，并改善了葡萄糖耐量，与胰岛素敏感性平行。这些发现表明，某些 SPM 和 SPM 前体（包括 17-HDHA 和 PD1）的生物合成受损，导致肥胖时脂肪组织炎症，并提示 17-HDHA 是肥胖相关并发症的一种新的治疗选择。
