Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands.
Department of Biology and Biological Engineering, Division of Chemical Biology, Chalmers University of Technology, Gothenburg, Sweden.
Diabetologia. 2020 Dec;63(12):2654-2664. doi: 10.1007/s00125-020-05266-6. Epub 2020 Sep 3.
AIMS/HYPOTHESIS: Intramyocellular lipid (IMCL) content associates with development of insulin resistance, albeit not in insulin-sensitive endurance-trained athletes (trained). Qualitative and spatial differences in muscle lipid composition may underlie this so-called athlete's paradox. Here we studied triacylglycerol (TAG) composition of individual myocellular lipid droplets (LDs) in trained individuals and individuals with type 2 diabetes mellitus.
Trained ([Formula: see text] 71.0 ± 1.6 ml O [kg lean body mass (LBM)] min), normoglycaemic (fasting glucose 5.1 ± 0.1 mmol/l) individuals and untrained ([Formula: see text] 36.8 ± 1.5 ml O [kg LBM] min) individuals with type 2 diabetes (fasting glucose 7.4 ± 0.5 mmol/l), with similar IMCL content (3.5 ± 0.7% vs 2.5 ± 0.3%, p = 0.241), but at opposite ends of the insulin sensitivity spectrum (glucose infusion rate 93.8 ± 6.6 vs 25.7 ± 5.3 μmol [kg LBM] min for trained individuals and those with type 2 diabetes, respectively) were included from our database in the present study. We applied in situ label-free broadband coherent anti-Stokes Raman scattering (CARS) microscopy to sections from skeletal muscle biopsies to measure TAG acyl chain length and saturation of myocellular LDs. This approach uniquely permits examination of individual LDs in their native environment, in a fibre-type-specific manner, taking into account LD size and subcellular location.
Despite a significant difference in insulin sensitivity, we observed remarkably similar acyl chain length and saturation in trained and type 2 diabetic individuals (chain length: 18.12 ± 0.61 vs 18.36 ± 0.43 number of carbons; saturation: 0.37 ± 0.05 vs 0.38 ± 0.06 number of C=C bonds). Longer acyl chains or higher saturation (lower C=C number) could be detected in subpopulations of LDs, i.e. large LDs (chain length: 18.11 ± 0.48 vs 18.63 ± 0.57 carbon number) and subsarcolemmal LDs (saturation: 0.34 ± 0.02 vs 0.36 ± 0.04 C=C number), which are more abundant in individuals with type 2 diabetes.
CONCLUSIONS/INTERPRETATION: In contrast to reports of profound differences in the lipid composition of lipids extracted from skeletal muscle from trained and type 2 diabetic individuals, our in situ, LD-specific approach detected only modest differences in TAG composition in LD subpopulations, which were dependent on LD size and subcellular location. If, and to what extent, these modest differences can impact insulin sensitivity remains to be elucidated. Graphical abstract.
目的/假设：肌细胞内脂质（IMCL）含量与胰岛素抵抗的发展有关，但在胰岛素敏感的耐力训练运动员（训练有素的）中并非如此。肌肉脂质组成的定性和空间差异可能是造成这种所谓的运动员悖论的原因。在这里，我们研究了训练有素的个体和 2 型糖尿病患者的单个肌细胞脂质滴（LD）中的三酰甘油（TAG）组成。
在我们的数据库中，纳入了具有相似 IMCL 含量（3.5±0.7%比 2.5±0.3%，p=0.241）但胰岛素敏感性谱处于相反两端的个体：有训练的个体[公式：见正文]71.0±1.6 ml O [kg瘦体重（LBM）] min），血糖正常（空腹血糖 5.1±0.1 mmol/l）和未训练的个体[公式：见正文]36.8±1.5 ml O [kg LBM] min）患有 2 型糖尿病（空腹血糖 7.4±0.5 mmol/l）。我们应用原位无标记宽带相干反斯托克斯拉曼散射（CARS）显微镜对骨骼肌活检切片进行检测，以测量肌细胞 LD 的 TAG 酰基链长和饱和度。这种方法独特地允许以纤维类型特异性的方式在其天然环境中检查单个 LD，并考虑到 LD 大小和亚细胞位置。
尽管胰岛素敏感性存在显著差异，但我们观察到训练有素的个体和 2 型糖尿病患者的酰基链长和饱和度非常相似（链长：18.12±0.61 比 18.36±0.43 个碳原子；饱和度：0.37±0.05 比 0.38±0.06 个 C=C 键）。可以在 LD 的亚群中检测到更长的酰基链或更高的饱和度（更低的 C=C 数），即大 LD（链长：18.11±0.48 比 18.63±0.57 个碳原子）和肌小节下 LD（饱和度：0.34±0.02 比 0.36±0.04 C=C 数），这些 LD 在 2 型糖尿病患者中更为丰富。
结论/解释：与从训练有素的个体和 2 型糖尿病患者的骨骼肌中提取的脂质的脂质组成存在深刻差异的报道相反，我们的原位、LD 特异性方法仅检测到 LD 亚群中 TAG 组成的适度差异，这取决于 LD 大小和亚细胞位置。这些适度的差异如果存在，以及在何种程度上会影响胰岛素敏感性，仍有待阐明。
