Paternal high-fat diet enhances offspring whole-body insulin sensitivity and skeletal muscle insulin signaling early in life.
Paternal high-fat diet enhances offspring whole-body insulin sensitivity and skeletal muscle insulin signaling early in life.
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DOI：
10.14814/phy2.13583
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发表时间：
2018-03
影响因子：
2.5
通讯作者：
Nowak FV
中科院分区：
文献类型：
--
作者：
Consitt LA;Saxena G;Slyvka Y;Clark BC;Friedlander M;Zhang Y;Nowak FV
有证据表明，父亲的饮食会使后代容易出现代谢功能障碍。尽管有这些知识，但关于父亲高脂肪喂养对后代胰岛素敏感性的影响知之甚少。本研究的目的是首次调查父亲高脂肪喂养对年轻和成年后代全身和骨骼肌胰岛素作用的影响。 4 周龄时，创始人 C57BL6/N 雄性 (F0) 被喂食高脂肪饮食或对照饮食 12 周，然后与采用对照饮食的雌性进行繁殖。后代 (F1) 在 6 周、6 个月或 12 个月时被安乐死，并在离体比目鱼肌中离体测量胰岛素刺激的胰岛素信号。 6 周龄时，与父亲对照相比，父亲高脂肪后代 (HFO) 的全身胰岛素敏感性增强（35%，P < 0.05），并且胰岛素刺激的 Akt 苏氨酸 308（70%，P < 0.05）和 AS160 苏氨酸 642（80%，P < 0.05）骨骼肌磷酸化增加喂养后代（CFO），尽管两个后代群体都食用标准食物。 6 个月大时，与 CFO 相比，HFO 的体脂百分比有所增加（74%，P < 0.005），全身和骨骼肌胰岛素信号也与 CFO 标准化。 HFO 中的体脂与胰岛素信号呈负相关，但 CFO 中则不然。这些发现表明，父亲的高脂肪喂养有助于增强 HFO 生命早期的全身和骨骼肌胰岛素敏感性。然而，这些好处在成年早期就会消失，可能是由于体内脂肪过早增加所致。
Evidence suggests that paternal diet can predispose offspring to metabolic dysfunction. Despite this knowledge, little is known regarding the effects of paternal high‐fat feeding on offspring insulin sensitivity. The purpose of this study was to investigate for the first time the effects of paternal high‐fat feeding on whole‐body and skeletal muscle insulin action in young and adult offspring. At 4 weeks of age, founder C57BL6/N males (F0) were fed a high‐fat diet or control diet for 12 weeks and then bred with females on a control diet. Offspring (F1) were euthanized at 6 weeks, 6 months, or 12 months and insulin‐stimulated insulin signaling was measured ex vivo in isolated soleus muscle. At 6 weeks of age, paternal high fat offspring (HFO) had enhanced whole‐body insulin sensitivity (35%, P < 0.05), as well as, increased insulin‐stimulated skeletal muscle phosphorylation of Akt threonine 308 (70%, P < 0.05) and AS160 threonine 642 (80%, P < 0.05) compared to paternal control fed offspring (CFO), despite both offspring groups consuming standard chow. At 6 months of age, HFO had increased percent body fat compared to CFO (74%, P < 0.005) and whole‐body and skeletal muscle insulin signaling normalized to CFO. Body fat was inversely related with insulin signaling in HFO, but not CFO. These findings suggest that paternal high‐fat feeding contributes to enhanced whole‐body and skeletal muscle insulin sensitivity in HFO early in life; however, these benefits are lost by early adulthood, potentially due to premature increases in body fat.