Davis Amanda N, Clegg J L, Perry C A, McFadden J W
Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, 26505, USA.
Cornell University, 264 Morrison Hall, Ithaca, NY, 14853, USA.
Lipids. 2017 Sep;52(9):771-780. doi: 10.1007/s11745-017-4287-5. Epub 2017 Aug 23.
The progression of insulin resistance in dairy cows represents a maternal adaptation to support milk production during heightened energy demand; however, excessive adipose tissue lipolysis can develop. In diabetic non-ruminants, the mechanisms that mediate insulin resistance involve the sphingolipid ceramide. We tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. Nine dairy cows were utilized in a replicated 3 × 3 Latin square design. Cows were ad libitum fed, nutrient-restricted (NR), or NR with nicotinic acid (NA; 5 mg of NA/h per kg BW; delivered i.v.) for 34 h. When provided access, cows were ad libitum fed a mixed ration of grass hay and ground corn to meet requirements. Intake for NR cows was limited to vitamins and minerals. Nicotinic acid was administered to suppress lipolysis. Saline was infused in cows not provided NA. At 32 and 33 h of treatment, a liver biopsy and insulin tolerance test were performed, respectively. Samples were analyzed using colorimetry, immunoassay, and mass spectrometry. Nutrient restriction increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, NA infusion was unable to prevent these responses. We also show that NR increases hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0-Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In conclusion, our results suggest that ceramide accrual represents a metabolic adaptation to nutrient restriction and impaired insulin action in dairy cows.
奶牛胰岛素抵抗的进展代表了母体在能量需求增加期间为支持产奶而进行的一种适应性变化；然而，可能会出现过度的脂肪组织脂解。在糖尿病非反刍动物中，介导胰岛素抵抗的机制涉及鞘脂神经酰胺。我们检验了这样一个假设，即神经酰胺在经历脂解和胰岛素抵抗的奶牛体内会蓄积。9头奶牛被用于重复的3×3拉丁方设计实验。奶牛分别接受自由采食、营养限制（NR）或营养限制加烟酸（NA；每千克体重每小时5毫克NA；静脉注射）处理34小时。在可自由采食时，奶牛自由采食由禾本科干草和粉碎玉米组成的混合日粮以满足营养需求。营养限制组奶牛的采食量仅限于维生素和矿物质。给予烟酸以抑制脂解。未给予NA的奶牛注射生理盐水。在处理的第32小时和第33小时，分别进行肝脏活检和胰岛素耐量试验。样本采用比色法、免疫测定法和质谱分析法进行分析。营养限制增加了血清脂肪酸和神经酰胺水平，并损害了胰岛素敏感性；然而，注射NA未能阻止这些反应。我们还表明，营养限制增加了肝脏神经酰胺的蓄积，这一反应与血清神经酰胺供应呈正相关。我们的数据表明，循环和肝脏中的24:0 - 神经酰胺与全身胰岛素耐量呈负相关，而16:0部分未观察到这种效应。总之，我们的结果表明，神经酰胺的蓄积代表了奶牛对营养限制和胰岛素作用受损的一种代谢适应性变化。
