To evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. Male C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). The HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. Treatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.

中文翻译：

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PPAR-α 和 γ 的抗脂肪变性作用涉及高脂肪饮食喂养小鼠的肠肝轴调节

评估 PPARα 和 PPARγ 激活（单独或联合）对肠肝轴的影响，强调高饱和脂肪饮食小鼠肠道屏障的完整性和肝脂肪变性。雄性 C57BL/6J 被喂食对照饮食 (C) 或高脂肪饮食 (HF) 十周。然后，开始为期 4 周的治疗：HF-α (WY14643)、HF-γ（低剂量吡格列酮）和 HF-αγ（组合）。心力衰竭导致超重、胰岛素抵抗、肠肝轴受损和明显的肝脂肪变性。治疗减少了体重，改善了葡萄糖稳态，并恢复了肠道微生物群多样性和肠道屏障基因表达。治疗还降低了血浆脂多糖浓度并有利于β-氧化基因，减少了肝脏中的巨噬细胞浸润和脂肪变性。 PPAR 激动剂治疗可调节肠道微生物群并恢复肠道屏障的完整性，从而减轻肝脏脂肪变性。这些结果表明这些激动剂有助于代谢相关脂肪肝疾病的治疗。