Effects of a 3-day fast on regional lipid and glucose metabolism in human skeletal muscle and adipose tissue.
OBJECTIVE
Fasting is characterized by increased whole body lipolysis and lipid oxidation, decreased glucose oxidation and insulin resistance. To identify the regional sources and underlying mechanisms, we studied 10 healthy male volunteers post-absorptively and after 72 h of fasting.


METHODS
Each study comprised a 3-h basal period and a 3-h hyperinsulinaemic euglycaemic clamp and we used a combination of leg and forearm arteriovenous techniques, upper and lower body microdialysis and glucose and palmitate tracers.


RESULTS
In the basal state, plasma levels, fluxes and oxidation rates of free fatty acids all roughly doubled after fasting. Palmitate fluxes across the forearm and leg also increased by two to threefold and interstitial leg muscle glycerol concentrations doubled. Subcutaneous femoral glycerol concentrations and blood flows were unaltered, but abdominal subcutaneous blood flow increased by 50% in the presence of unchanged glycerol concentrations, indicating stimulated abdominal lipolysis. During the clamp, we observed whole body insulin resistance and glucose uptake across the leg and forearm decreased by 60%.


CONCLUSIONS
Our data show that fasting induces insulin resistance in upper and lower body muscles and suggest that increased lipolysis, is primarily due to the activation of lipolysis in muscle-associated fat (in the leg) and in upper body subcutaneous fat, whereas peripheral subcutaneous fat is spared.
Gjedsted
J
J
Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Noerrebrogade, Aarhus, Denmark. jakobgjedsted@dadlnet.dk
Gormsen
L C
LC
Nielsen
S
S
Schmitz
O
O
Djurhuus
C B
CB
Keiding
S
S
Ørskov
H
H
Tønnesen
E
E
Møller
N
N
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001132:Arm; D002153:Calorimetry, Indirect; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D007553:Isotope Labeling; D007866:Leg; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism / Q000494:pharmacology; D050151:Subcutaneous Fat / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism; D015431:Weight Loss