Consitt Leslie A, Saxena Gunjan, Slyvka Yuriy, Clark Brian C, Friedlander Max, Zhang Yizhu, Nowak Felicia V
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.
Diabetes Institute, Ohio University, Athens, Ohio, USA.
Physiol Rep. 2018 Mar;6(5). doi: 10.14814/phy2.13583.
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.
有证据表明，父本饮食可使后代易患代谢功能障碍。尽管有这方面的认知，但关于父本高脂喂养对后代胰岛素敏感性的影响却知之甚少。本研究的目的是首次调查父本高脂喂养对幼年和成年后代全身及骨骼肌胰岛素作用的影响。4周龄时，将初代C57BL6/N雄性小鼠（F0）喂食高脂饮食或对照饮食12周，然后与喂食对照饮食的雌性小鼠交配。后代（F1）在6周、6个月或12个月时安乐死，并在离体比目鱼肌中体外测量胰岛素刺激的胰岛素信号传导。6周龄时，与父本对照喂养的后代（CFO）相比，父本高脂后代（HFO）的全身胰岛素敏感性增强（35%，P<0.05），同时胰岛素刺激的骨骼肌中Akt苏氨酸308（70%，P<0.05）和AS160苏氨酸642（80%，P<0.05）的磷酸化增加，尽管两个后代组都食用标准食物。6个月龄时，与CFO相比，HFO的体脂百分比增加（74%，P<0.005），全身和骨骼肌胰岛素信号传导恢复至CFO水平。在HFO中，体脂与胰岛素信号呈负相关，但在CFO中并非如此。这些发现表明，父本高脂喂养有助于HFO在生命早期增强全身和骨骼肌胰岛素敏感性；然而，这些益处到成年早期就消失了，可能是由于体脂过早增加所致。
