Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients.
OBJECTIVE
In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients.


METHODS
We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type.


RESULTS
Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05).


CONCLUSIONS
This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.
van Loon
L J C
LJ
Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. L.vanLoon@HB.Unimaas.nl
Manders
R J F
RJ
Koopman
R
R
Kaastra
B
B
Stegen
J H C H
JH
Gijsen
A P
AP
Saris
W H M
WH
Keizer
H A
HA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000368:Aged; D000465:Algorithms; D001823:Body Composition; D015992:Body Mass Index; D001944:Breath Tests; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology; D005080:Exercise Test; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000097:blood; D011719:Pyrazines / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D010168:Palmitates; D011719:Pyrazines; D006003:Glycogen; C027696:acipimox