Plasma ceramides are elevated in overweight Holstein dairy cows experiencing greater lipolysis and insulin resistance during the transition from late pregnancy to early lactation.
Plasma ceramides are elevated in overweight Holstein dairy cows experiencing greater lipolysis and insulin resistance during the transition from late pregnancy to early lactation.
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DOI：
10.3168/jds.2015-9519
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发表时间：
2015-11
影响因子：
3.5
通讯作者：
McFadden JW
中科院分区：
文献类型：
--
作者：
Rico JE;Bandaru VV;Dorskind JM;Haughey NJ;McFadden JW
胰岛素抵抗是奶牛从妊娠晚期向泌乳早期过渡时对分娩的一种顺势而为的适应。围产期奶牛脂肪过多的增加会使其更易发生脂解和胰岛素抵抗，从而增加代谢性疾病的风险。超重围产期奶牛胰岛素抵抗发生的机制可能取决于神经酰胺代谢。鞘脂神经酰胺在超重单胃动物的血浆和组织中积累，并促进饱和脂肪酸诱导的胰岛素抵抗。考虑到这一证据，我们假设，血浆神经酰胺将在围产期奶牛升高，这些鞘脂将与脂解和胰岛素抵抗的程度。为了检验我们的中心假设，将经产荷斯坦奶牛根据其在d-30泌乳时的身体状况评分（BCS）分为2组：瘦（BCS <3.0; n = 10）或超重（BCS> 4.0; n = 11）。在相对于预期分娩的d-45、d-30、d-15和d-7以及产后d 4采集血样。测量血糖、胰岛素、非酯化脂肪酸（NEFA）和β-羟基丁酸（BHBA）浓度，并估计胰岛素敏感性。使用基于液相色谱的质谱法测定个体血浆神经酰胺和糖基化神经酰胺的浓度。结果表明，更大的肥胖与更大的损失在身体状况在怀孕后期。超重奶牛的循环葡萄糖、胰岛素和NEFA浓度较高，胰岛素敏感性较低。我们检测到30种不同的鞘脂，横跨6个脂质类，酰基链范围从16到26个碳。检测到的最丰富的血浆鞘脂为C24：0-神经酰胺、C24：0-单己糖神经酰胺和C16：0-乳糖神经酰胺。总神经酰胺和monohexosylceramide的血浆浓度随着泌乳期的临近而增加，并且饱和神经酰胺和monohexosylceramide在相对于具有瘦表型的具有更大肥胖的奶牛中升高。血浆神经酰胺（例如，C24：0-神经酰胺）与血浆NEFA呈正相关，与胰岛素敏感性呈负相关。我们的数据表明，从妊娠晚期过渡到哺乳期的奶牛中，血浆鞘脂组重塑，其特征在于血浆神经酰胺伴随着围产期胰岛素抵抗的发展而增加。
Insulin resistance is a homeorhetic adaptation to parturition in dairy cows transitioning from late pregnancy to early lactation. An increase in prepartum adiposity can predispose periparturient cows to greater lipolysis and insulin resistance, thus increasing the risk for metabolic disease. Mechanisms mediating the development of insulin resistance in overweight peripartal dairy cows may depend on ceramide metabolism. The sphingolipid ceramide accumulates in plasma and tissues of overweight monogastric animals, and facilitates saturated fatty acid-induced insulin resistance. Considering this evidence, we hypothesized that plasma ceramides would be elevated in periparturient dairy cattle and that these sphingolipids would correlate with the magnitude of lipolysis and insulin resistance. To test our central hypothesis, multiparous Holstein cows were allocated into 2 groups according to their body condition score (BCS) at d −30 prepartum: lean (BCS <3.0; n = 10) or overweight (BCS >4.0; n = 11). Blood samples were collected at d −45, −30, −15, and −7, relative to expected parturition, and at d 4 postpartum. Plasma glucose, insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate (BHBA) concentrations were measured, and insulin sensitivity was estimated. The concentrations of individual plasma ceramide and glycosylated ceramide were determined using liquid chromatography-based mass spectrometry. Results demonstrated that greater adiposity was associated with a greater loss in body condition during late pregnancy. Overweight cows had greater circulating concentrations of glucose, insulin, and NEFA, and lower insulin sensitivity relative to lean cows. We detected 30 different sphingolipids across 6 lipid classes with acyl chains ranging from 16 to 26 carbons. The most abundant plasma sphingolipids detected were C24:0-ceramide, C24:0-monohexosylceramide, and C16:0-lactosylceramide. Plasma concentrations of total ceramide and monohexosylceramide increased as lactation approached, and saturated ceramide and monohexosylceramide were elevated in cows with greater adiposity relative to those with a lean phenotype. Plasma ceramides (e.g., C24:0-ceramide) were positively correlated with plasma NEFA and inversely correlated with insulin sensitivity. Our data demonstrate a remodeled plasma sphingolipidome in dairy cows transitioning from late pregnancy to lactation characterized by a concomitant increase in plasma ceramides with the development of peripartal insulin resistance.
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影响因子：
3.9
作者：
Lightle, S;Tosheva, R;Nikolova-Karakashian, M
通讯作者：
Nikolova-Karakashian, M
影响因子：
2
作者：
Cuschieri, Joseph;Bulger, Eileen;Maier, Ronald V
通讯作者：
Maier, Ronald V
影响因子：
2.5
作者：
Bell, Alan W.;Bauman, Dale E.
通讯作者：
Bauman, Dale E.
影响因子：
29
作者：
Holland, William L.;Brozinick, Joseph T.;Summers, Scott A.
通讯作者：
Summers, Scott A.
影响因子：
2.1
作者：
Holtenius P;Holtenius K
通讯作者：
Holtenius K