Transcriptome analysis of mice adipose tissues

We report that the HF/HS-mediated functional enrichment of genes of immunity and inflammation is driven toward normal by the AOF supplementation Obesity may not constantly associate with metabolic disorders and mortality later in life, raising the challenging concept of healthy obesity. Here, high fat-high sucrose (HF/HS) feeding produces hyperglycaemia and hypercholesterolemia, increases oxidative stress, elevates endotoxemia, expands adipose tissue (with enlarged adipocytes, macrophage infiltration and accumulation of cholesterol and oxysterols), and reduces lifespan of obese mice. Despite persistence of obesity, supplementation with an antioxidant formulation normalizes plasma lipids and endotoxemia, prevents macrophage recruitment in adipose tissue, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends lifespan. The HF/HS-mediated functional enrichment of genes of immunity and inflammation (in particular response to lipopolysaccharides) is driven towards normal by the antioxidant formulation. It is concluded that the limitation of immune cell infiltration in adipose tissue on the long term by an antioxidant formulation can increase lifespan independently of body weight and fat storage. It constitutes the hallmark of a healthy adiposity trait. Examination of the expression profile of mice adipose tissues fed either standard (Std), High-fat/high-sucrose (HF/HS) or HF/HS + antioxidant formulation (AOF) for 180 days

本研究表明，抗氧化剂配方（antioxidant formulation, AOF）可使高脂高糖（high fat-high sucrose, HF/HS）介导的免疫与炎症相关基因功能富集恢复至正常水平。肥胖未必始终与晚年代谢紊乱及死亡风险相关，这引出了“健康肥胖”这一具有挑战性的概念。本研究中，高脂高糖（HF/HS）喂养可诱导肥胖小鼠出现高血糖与高胆固醇血症，加剧氧化应激，升高内毒素血症水平，引发脂肪组织扩张（表现为脂肪细胞肥大、巨噬细胞浸润以及胆固醇与氧甾醇堆积），并缩短其寿命。即便肥胖状态持续存在，抗氧化剂配方干预可使血浆脂质与内毒素血症恢复正常，抑制脂肪组织内巨噬细胞募集，减少脂肪组织中胆固醇与氧化胆固醇的堆积，并延长小鼠寿命。抗氧化剂配方可使HF/HS介导的免疫与炎症相关基因（尤其是脂多糖（lipopolysaccharides）应答相关基因）功能富集恢复至正常水平。综上，抗氧化剂配方通过长期抑制脂肪组织内免疫细胞浸润，可在不依赖体重与脂肪储存的前提下延长小鼠寿命。这一现象构成了健康肥胖表型的标志性特征。本研究对分别饲喂标准饲料（Std）、高脂高糖饲料（HF/HS）以及高脂高糖+抗氧化剂配方（AOF）的小鼠，进行了为期180天的脂肪组织基因表达谱分析。