Label-free CARS microscopy reveals similar triacylglycerol acyl chain length and saturation in myocellular lipid droplets of athletes and individuals with type 2 diabetes
Artikel i vetenskaplig tidskrift, 2020

Aims/hypothesis: Intramyocellular lipid (IMCL) content associates with development of insulin resistance, albeit not in insulinsensitive 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.
Methods: Trained (˙V O2max 71.0 ± 1.6 ml O2 [kg lean body mass (LBM)]−1 min−1), normoglycaemic (fasting glucose 5.1 ± 0.1 mmol/l) individuals and untrained (V O2max 36.8 ± 1.5 ml O2 [kg LBM]−1 min−1) 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]−1 min−1 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.
Results: 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.

Lipid droplet chemical composition

Type 2 diabetes

Lipid droplets

Lipid composition

Athlete’s paradox

CARS microscopy

Intramyocellular lipid storage

Författare

Sabine Daemen

Maastricht University Medical Center

Anne Gemmink

Maastricht University Medical Center

Alexandra Paul

Chalmers, Biologi och bioteknik, Kemisk biologi

Nils Billecke

Max Planck Institute for Polymer Research

Katrina Rieger

Max Planck Institute for Polymer Research

Sapun H. Parekh

The University of Texas at Austin

Matthijs K.C. Hesselink

Maastricht University Medical Center

Diabetologia

0012-186X (ISSN) 1432-0428 (eISSN)

Vol. In Press

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Vetenskapsrådet (VR), 2019-07-01 -- 2022-06-30.

Ämneskategorier

Endokrinologi och diabetes

Cell- och molekylärbiologi

Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi

Fundament

Grundläggande vetenskaper

DOI

10.1007/s00125-020-05266-6

Mer information

Senast uppdaterat

2020-09-22