Endurance training increases skeletal muscle LKB1 and PGC-1α protein abundance: effects of time and intensity

Abstract

Recent research suggests that LKB1 is the major AMP-activated protein kinase kinase (AMPKK). Peroxisome-proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) is a master coordinator of mitochondrial biogenesis. Previously we reported that skeletal muscle LKB1 protein increases with endurance training. The purpose of this study was to determine whether training-induced increases in skeletal muscle LKB1 and PGC-1␣ protein exhibit a time course and intensity-dependent response similar to that of citrate synthase. Male Sprague-Dawley rats completed endurance-and interval-training protocols. For endurance training, rats trained for 4, 11, 25, or 53 days. Interval-training rats trained identically to endurance-trained rats, except that after 25 days interval training was combined with endurance training. Time course data were collected from endurance-trained red quadriceps (RQ) after each time point. Interval training data were collected from soleus, RQ, and white quadriceps (WQ) muscle after 53 days only. Mouse protein 25 (MO25) and PGC-1␣ protein increased significantly after 4 days. Increased citrate synthase activity, increased LKB1 protein, and decreased AMPKK activity were found after 11 days. Maximal increases occurred after 4 days for hexokinase II, 25 days for MO25, and 53 days for citrate synthase, LKB1, and PGC-1␣. In WQ, but not RQ or soleus, interval training had an additive effect to endurance training and induced significant increases in all proteins measured. These results demonstrate that LKB1 and PGC-1␣ protein abundances increase with endurance and interval training similarly to citrate synthase. The increase in LKB1 and PGC-1␣ with endurance and interval training may function to maintain the traininginduced increases in mitochondrial mass. adenosine 5Ј-monophosphate-activated protein kinase, AMP-activated protein kinase kinase; diabetes; MO25, Ste-20-related adaptor protein THE INCIDENCE OF TYPE 2 DIABETES and obesity is increasing at an alarming rate. As of 2002, 8.7% of Americans over age 20 yr and 18.3% of Americans over age 60 yr were diabetic (1). Type 2 diabetes is strongly associated with obesity and is characterized primarily by a reduction in insulin-stimulated glucose uptake. Type 2 diabetes is often accompanied by a decreased skeletal muscle mitochondrial content and a higher-than-normal proportion of type IIx (IIb) muscle fibers (9,24,31,37,48). Regular exercise prevents type 2 diabetes directly by increasing insulin sensitivity and indirectly by decreasing adiposity. Physical activity also increases skeletal muscle mitochondrial mass and induces an increased expression of type IIa myosin heavy chain (MHC) and a decreased expression of type IIx (IIb) MHC (40). Training intensity regulates fiber typespecific training adaptations (2, 57). Higher-intensity training is required for the maximal recruitment and training of type IIx (IIb) fibers (16,46). Hence, interval training might be particularly important for type 2 diabetics.Research during the past decade has characterized some of t...

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“…Here, our data suggest that LKB1 regulation of TRB3 expression occurs through the PGC1␣/PPAR␣ pathway in skeletal muscle. Previous reports on skeletal muscle have shown that increases in LKB1 protein with chronic exercise training (45) and activation of AMPK via AICAR (24,26,43) correlate with increases in PGC1␣ expression in skeletal muscle. Given that AMPK␣2 is required for the AICAR effect in skeletal muscle (24), it seems plausible that the reductions in AMPK␣2 activity in MLKB1KO muscle may partially mediate the decreases in PGC1␣ and PPAR␣ expression.…”

Whole body overexpression of PGC-1α has opposite effects on hepatic and muscle insulin sensitivity

“…In rodents (2,15,34,46) and humans (33,44), acute exercise induces PGC-1␣ gene expression in muscle. It has been proposed that this increase in muscle PGC-1␣ expression after prolonged exercise mediates the insulin-sensitizing effects (16).…”

PGC-1 coactivators: inducible regulators of energy metabolism in health and disease

“…Studies in rodent models indicate that both short-term exercise and endurance training activate PGC-1α expression in skeletal muscle (34,35,64,65). Subsequent studies in humans have further demonstrated remarkable inducibility of PGC-1α in response to acute bouts of exercise or endurance training (38,66) and have indicated that PGC-1α levels are increased mainly in type IIa fibers after endurance training (66).…”