Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

母亲在怀孕期间锻炼 (ME) 已被证明可以改善后代的代谢健康，并可以防止非酒精性脂肪肝 (NAFLD) 的发展。然而，其潜在机制仍知之甚少，并且尚不清楚是否已经在后代早期发现了对肝脏代谢的保护作用。本研究旨在确定妊娠期间 ME 对后代身体成分和 NAFLD 发展的影响，同时侧重于对生命早期发育器官编程过程中肝脏能量代谢的蛋白质组学分析。在致肥高脂肪饮食 (HFD) 下，经过锻炼的 C57BL/6J 小鼠母鼠的雄性后代在成年期（产后第 112 天）不受体重增加和 NAFLD 的影响。这与肝脏 AMP 激活蛋白激酶 (AMPK)、过氧化物酶体增殖物激活受体 α (PPARα) 和 PPAR 辅激活因子-1 α (PGC1α) 信号的显着激活有关，从而减少肝脏脂肪生成并增加器官编程时的肝脏 β-氧化生命早期的高峰（P21）。伴随的蛋白质组学分析揭示了由于 ME 对胆固醇 7 α-羟化酶 (CYP7A1) 影响最显着的后代的特征性肝脏表达模式。因此，ME 可以通过塑造生命早期的肝脏蛋白质组学特征和代谢，为后代 HFD 诱导的 NAFLD 提供保护。结果强调了怀孕期间运动在预防 NAFLD 早期起源方面的潜力。过氧化物酶体增殖物激活受体 α (PPARα) 和 PPAR coactivator-1 α (PGC1α) 信号在生命早期的器官编程高峰期减少肝脏脂肪生成和增加肝脏 β-氧化 (P21)。伴随的蛋白质组学分析揭示了由于 ME 对胆固醇 7 α-羟化酶 (CYP7A1) 影响最显着的后代的特征性肝脏表达模式。因此，ME 可以通过塑造生命早期的肝脏蛋白质组学特征和代谢，为后代 HFD 诱导的 NAFLD 提供保护。结果强调了怀孕期间运动在预防 NAFLD 早期起源方面的潜力。过氧化物酶体增殖物激活受体 α (PPARα) 和 PPAR coactivator-1 α (PGC1α) 信号在生命早期的器官编程高峰期减少肝脏脂肪生成和增加肝脏 β-氧化 (P21)。伴随的蛋白质组学分析揭示了由于 ME 对胆固醇 7 α-羟化酶 (CYP7A1) 影响最显着的后代的特征性肝脏表达模式。因此，ME 可以通过塑造生命早期的肝脏蛋白质组学特征和代谢，为后代 HFD 诱导的 NAFLD 提供保护。结果强调了怀孕期间运动在预防 NAFLD 早期起源方面的潜力。伴随的蛋白质组学分析揭示了由于 ME 对胆固醇 7 α-羟化酶 (CYP7A1) 影响最显着的后代的特征性肝脏表达模式。因此，ME 可以通过塑造生命早期的肝脏蛋白质组学特征和代谢，为后代 HFD 诱导的 NAFLD 提供保护。结果强调了怀孕期间运动在预防 NAFLD 早期起源方面的潜力。伴随的蛋白质组学分析揭示了由于 ME 对胆固醇 7 α-羟化酶 (CYP7A1) 影响最显着的后代的特征性肝脏表达模式。因此，ME 可以通过塑造生命早期的肝脏蛋白质组学特征和代谢，为后代 HFD 诱导的 NAFLD 提供保护。结果强调了怀孕期间运动在预防 NAFLD 早期起源方面的潜力。