Center for Nutrition Research and Department of Nutrition, Food Sciences and Physiology, University of Navarra, 31008 Pamplona, Spain.
Navarra's Health Research Institute (IdiSNA), 31008 Pamplona, Spain.
Nutrients. 2021 Feb 3;13(2):501. doi: 10.3390/nu13020501.
Obesity and aging are associated to non-alcoholic fatty liver disease (NAFLD) development. Here, we investigate whether long-term feeding with a docosahexaenoic acid (DHA)-enriched diet and aerobic exercise, alone or in combination, are effective in ameliorating NAFLD in aged obese mice. Two-month-old female C57BL/6J mice received control or high fat diet (HFD) for 4 months. Then, the diet-induced obese (DIO) mice were distributed into four groups: DIO, DIO + DHA (15% dietary lipids replaced by a DHA-rich concentrate), DIO + EX (treadmill running), and DIO + DHA + EX up to 18 months. The DHA-rich diet reduced liver steatosis in DIO mice, decreasing lipogenic genes (, and upregulated lipid catabolism genes (/) expression. A similar pattern was observed in the DIO + EX group. The combination of DHA + exercise potentiated an increase in and genes, and AMPK activation, key regulators of fatty acid oxidation. Exercise, alone or in combination with DHA, significantly reversed the induction of proinflammatory genes (, ) in DIO mice. DHA supplementation was effective in preventing the alterations induced by the HFD in endoplasmic reticulum stress-related genes () and autophagy markers (LC3II/I ratio, p62, ). In summary, long-term DHA supplementation and/or exercise could be helpful to delay NAFLD progression during aging in obesity.
肥胖和衰老与非酒精性脂肪性肝病（NAFLD）的发展有关。在这里，我们研究了长期用富含二十二碳六烯酸（DHA）的饮食和有氧运动单独或联合喂养是否能有效改善肥胖老年小鼠的 NAFLD。将 2 个月大的雌性 C57BL/6J 小鼠用对照或高脂肪饮食（HFD）喂养 4 个月。然后，将饮食诱导肥胖（DIO）小鼠分为四组：DIO、DIO+DHA（15%的膳食脂质被富含 DHA 的浓缩物取代）、DIO+EX（跑步机跑步）和 DIO+DHA+EX，直到 18 个月。富含 DHA 的饮食减少了 DIO 小鼠的肝脂肪变性，降低了脂肪生成基因（、和）的表达，并上调了脂质分解代谢基因（/）的表达。在 DIO+EX 组中观察到类似的模式。DHA+运动的组合增强了脂肪酸氧化的关键调节因子（和）基因和 AMPK 的激活。运动，单独或与 DHA 联合使用，可显著逆转 DIO 小鼠中促炎基因（、）的诱导。DHA 补充有效地预防了 HFD 诱导的内质网应激相关基因（）和自噬标记物（LC3II/I 比、p62、）的改变。总之，长期 DHA 补充和/或运动有助于延缓肥胖老年小鼠 NAFLD 的进展。
