Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog...
Transcript of Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog...
![Page 1: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/1.jpg)
Muscle lipid storage, insulin sensitivity and oxidative capacity; a
microscopic approach
Sabine Daemen17-02-17Diabetes and Metabolism Research Groupdmrg.nl
![Page 2: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/2.jpg)
Athletes Paradox
Pan et al. 1997 Diabetes
Goodpaster et al. 2004 Obes Res
![Page 3: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/3.jpg)
Lipid droplets (LDs)
Morphology
Cellulardistribution
Coating proteins; PLIN5
Contact withmitochondria
Composition
Role for lipid droplets and their coat proteins in insulin sensitivity in skeletal muscle?
![Page 4: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/4.jpg)
Aim
1. Morphology
2. Cellulardistribution
3. Coating proteins; PLIN5
4. Contact withmitochondria
5. Composition
Type 2 diabetes patients (T2D)
Endurance-trainedathletes
![Page 5: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/5.jpg)
Methods morphology & localization
• Muscle biopsies: 7 μm thick sections• Staining:
- Bodipy for lipid droplets (green)- Laminin for cell membrane (blue)- MHC1 for fibertyping
• Confocal microscopy (Leica TCS SPE)• Deconvolution• Image Analysis (ImageJ & Matlab®)
1. Morphology & 2. Localization
![Page 6: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/6.jpg)
Intramyocellular lipid (IMCL) storage is fiber type specific
All Type I Type II0.0
0.5
1.0
1.5
2.0
*
#
Athletes
T2D
IMC
L c
on
ten
t (%
lip
id a
rea f
racti
on
)
1. Morphology
Type I Type II0.0
0.1
0.2
0.3
0.4
0.5
* # Athletes
T2D
LD
siz
e (
m2)
Type I Type II0.00
0.02
0.04
0.06
0.08
Athletes
T2D
*
# #
LD
nu
mb
er
(# /
m2)
![Page 7: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/7.jpg)
Increased subsarcolemmal lipid storage in T2D
2. Localization
SS IMF SS IMF0.0
0.5
1.0
1.5
2.0
2.5
Type I Type II
*
*
T2D
Athletes
IMC
L c
on
ten
t (%
lip
id a
rea f
racti
on
)
Type I Type II0
5
10
15
20
25
T2D
Athletes
*
*
Fra
cti
on
SS
LD
s (
%)
Subsarcolemmal (SS) lipid dropletsIntermyofibrillar (IMF) lipid droplets
Gemmink 2015 Diapedia
![Page 8: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/8.jpg)
PLIN5 coating
3. PLIN5 coating
PLIN5 LDs Cel membrane
Insulin sensitivityIMCL
Bosma et al. 2013 Biochim Biophys Acta
![Page 9: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/9.jpg)
PLIN5 coating does nog associate with improved insulin sensitivity
0.0 0.5 1.00
50
100
150 AthletesLeanObeseT2D
PLIN5+ Lipid Area Fraction (%)
GIR
(
mo
l/kg
le
an
ma
ss/m
in)
Ath
lete
s
Lean
Obes
eT2D
0.0
0.5
1.0
1.5
2.0
#*
* *
PL
IN5 p
rote
in (
AU
)
3. PLIN5 coating
![Page 10: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/10.jpg)
Differential LD-mitochondrial contact in type 2 fibers
All Type I Type II0.0
0.1
0.2
0.3
*
# Athletes
T2D
Mit
o a
rea
fra
cti
on
(%
)
4. Contact with mitochondria
LD Mitochondria
![Page 11: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/11.jpg)
LD composition by CARS microscopy
5. Composition
In collaboration with Dr. Sapun Parekh, Max Planck Institute for Polymer Research, Mainz
Billecke et al. 2015 Integr Biol
![Page 12: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/12.jpg)
Working at the Max Planck Institute Mainz
• Technical Institute
• Partly home-build CARS microscope
5. Composition
![Page 13: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/13.jpg)
Only subtle differences in CARS spectra
*
*
*** ***
***
5. Composition
Related to saturation and chain length
![Page 14: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/14.jpg)
Differences especially in type 2 fibers
*
*
***
*** ***
5. Composition
![Page 15: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/15.jpg)
Conclusions
• Differential lipid storage pattern between Athletes and T2D- Fiber type specific- Higher number of LDs in athletes <> larger LDs in T2D- More lipid storage in SS area in T2D
• PLIN5 coating of LDs does not directly explain the athletes paradox
• LD-mitochondrial contact differs in type 2 fibers between Athletes and T2D
• Only minor differences in lipid composition of the LD between Athletes and T2D
![Page 16: Muscle lipid storage, insulin sensitivity and oxidative capacity ... Symp...PLIN5 coating does nog associate with improved insulin sensitivity 0.0 0.5 1.0 0 50 100 150 Athletes Lean](https://reader036.fdocuments.us/reader036/viewer/2022090506/601c5df40cec4d4e332da4ec/html5/thumbnails/16.jpg)
Acknowledgements
Department of Human Biology and Movement Sciences: • Anne Gemmink• Bram Brouwers• Gert Schaart• Joris Hoeks• Patrick Schrauwen• Matthijs K.C. Hesselink
Department of Molecular Spectroscopy, Max Planck Institute for Polymer Research Mainz
• Nils Billecke• Sapun Parekh
Graduate Programme
Diabetes and Metabolism Research Group: www.dmrg.nlfacebook.com/diabetesmaastricht