Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Department of Endocrinology, Diabetes and Metabolism, Copenhagen University Hospital, Copenhagen, Denmark.
Sci Rep. 2018 Feb 22;8(1):3452. doi: 10.1038/s41598-018-21419-5.
Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. We hypothesised that LBW individuals exhibit an increased fatty acid flux into lipogenesis in non-adipose tissue with a resulting accumulation of lipotoxic lipids, including ceramides, in the blood. Therefore, we measured fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet by HPLC-HRMS. LBW men did not show elevated plasma ceramide levels after the control or high-fat, high-calorie diet. An increased fatty acid oxidation rate in these individuals during both diets may limit ceramide synthesis and thereby compensate for a likely increased fatty acid load to non-adipose tissue. Interestingly, LBW and NBW men decreased d18:0-18:1/d18:1-18:0 and d18:1-24:2/d18:2-24:1 levels and increased the d18:0-24:1a level in response to overfeeding. Plasma d18:0-24:1a and total ceramide levels were positively associated with the fasting blood glucose level and endogenous glucose production after the control diet, and the total ceramide level was in addition positively associated with hepatic insulin resistance. Further studies are needed to determine if lipotoxicity contributes to insulin resistance in LBW individuals.
低出生体重（LBW）个体发生胰岛素抵抗和 2 型糖尿病的风险高于正常出生体重（NBW）个体。我们假设 LBW 个体在非脂肪组织中表现出脂肪酸流入脂肪生成的增加，导致血液中包括神经酰胺在内的脂毒性脂质的积累。因此，我们通过 HPLC-HRMS 测量了 18 名年轻、健康的 LBW 男性和 25 名 NBW 对照者在等热量控制饮食和 5 天高脂肪、高卡路里饮食后的空腹血浆中 27 种神经酰胺的水平。LBW 男性在对照饮食或高脂肪、高卡路里饮食后，血浆神经酰胺水平并没有升高。在这两种饮食中，这些个体的脂肪酸氧化率增加可能会限制神经酰胺的合成，从而补偿非脂肪组织中可能增加的脂肪酸负荷。有趣的是，LBW 和 NBW 男性在过食时降低了 d18:0-18:1/d18:1-18:0 和 d18:1-24:2/d18:2-24:1 的水平，并增加了 d18:0-24:1a 的水平。血浆 d18:0-24:1a 和总神经酰胺水平与对照饮食后的空腹血糖水平和内源性葡萄糖生成呈正相关，总神经酰胺水平与肝胰岛素抵抗呈正相关。还需要进一步的研究来确定脂毒性是否导致 LBW 个体的胰岛素抵抗。
