Effect of training status on regional disposal of circulating free fatty acids in the liver and skeletal muscle during physiological hyperinsulinemia
: Iozzo P, Takala T, Oikonen V, Bergman J, Grönroos T, Ferrannini E, Nuutila P, Knuuti J
Publisher: American Diabetes Association (United States)
: 2004
: 27
: 9
: 2172
: 2177
: 6
DOI: https://doi.org/NA
OBJECTIVE:
Fat
metabolism is increasingly implicated in the pathogenesis of type 2
diabetes. Endurance training has been shown to prevent hepatic steatosis
and to alter skeletal muscle fat metabolism, and regional free fatty
acid (FFA) uptake adaptations were suggested as a mechanism. Thus, we
tested whether endurance training modifies the uptake of plasma FFAs
occurring in the liver and in skeletal muscle during anabolic, i.e.,
hyperinsulinemic, conditions.
Trained
and untrained healthy male subjects underwent positron emission
tomography scanning of the liver and thigh regions, with the FFA analog
14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid, during euglycemic
hyperinsulinemia. Tracer influx rate constants in skeletal muscle
(MK(i)) and liver (LK(i)) were multiplied by plasma FFA levels to obtain
FFA uptake for skeletal muscle (MFU) and liver (LFU), respectively.
Athletes
showed increased Vo(2max) (P < 0.0001), insulin-mediated glucose
disposal (M value, 61 +/- 4 vs. 46 +/- 3 micromol. min(-1). kg(-1), P =
0.01), and plasma lactate levels during the clamp and lower percentage
of body fat mass (P = 0.002). MK(i) was 25% higher in athletes than in
sedentary men (P = 0.03). In all subjects, MK(i) and MFU were positively
correlated with the M value (r = 0.56, P = 0.02, and r = 0.51, P =
0.03, respectively) and with plasma lactate levels (r = 0.63, P = 0.006,
and r = 0.63, P = 0.005, respectively). LK(i) was significantly reduced
by 20% in the athletes (P = 0.04). By multiple regression, LFU was
inversely correlated with the two fitness categories (P = 0.008), and it
was lower in athletes. Linear fitting of liver data showed time
consistency, indicating no release of FFAs as a mechanism for the
reduced liver retention in athletes.
We
conclude that endurance training promotes insulin-mediated glucose and
FFA disposal in skeletal muscle, while lowering hepatic FFA uptake. Such
changes may result in a divergent pattern of fat accumulation in the
two organs.