Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr(172) phosphorylation before training and higher exercise-induced ACC2 Ser(221) phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of Vo2peak), the acute exercise response on AMPK Thr(172), ACC2 Ser(221), AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser(221) phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.

International audienceThe aim of this study was to test the hypotheses that 1) skeletal muscles of elderly subjects can adapt to a single endurance exercise bout and 2) endurance trained elderly subjects have higher expression/activity of oxidative and angiogenic proteins in skeletal muscle than untrained elderly people. To investigate this, lifelong endurance trained elderly (ET; n=8) aged 71.3±3.4years and untrained elderly subjects (UT; n=7) aged 71.3±4years, performed a cycling exercise bout at 75% VO2max with vastus lateralis muscle biopsies obtained before (Pre), immediately after exercise and at 2h of recovery. Capillarization was detected histochemically and oxidative enzyme activities were determined on isolated mitochondria. GLUT4, HKII, Cyt c and VEGF protein expression was measured on muscle lysates from Pre-biopsies, phosphorylation of AMPK and P38 on lysates from Pre and 0' biopsies, while PGC-1α, VEGF, HKII and TFAM mRNA content was determined at all time points. ET had ~30% higher PDH, CS, SDH, α-KG-DH and ATP synthase activities and ~20% higher capillarization than UT, reflecting increased skeletal muscle oxidative capacity with lifelong endurance exercise training. In addition, acute exercise increased PGC-1α mRNA 11-fold and VEGF mRNA 4-fold at 2h of recovery in UT, and AMPK phosphorylation ~5-fold immediately after exercise, relative to Pre, indicating an ability to adapt metabolically and angiogenically to endurance exercise. However, in ET PGC-1α mRNA only increased 5 fold and AMPK phosphorylation ~2-fold, while VEGF mRNA remained unchanged after the acute exercise bout. P38 increased similarly in ET and UT after exercise. In conclusion, the present findings suggest that lifelong endurance exercise training ensures an improved oxidative capacity of skeletal muscle, and that skeletal muscle of elderly subjects maintains the ability to respond to acute exercise

The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue.

Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1α knockout (KO), muscle specific PGC-1α KO (MKO) and muscle-specific PGC-1α overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFα mRNA content was lower in skeletal muscle of whole body PGC-1α KO mice and in accordance TG mice showed increased TNFα mRNA and protein level relative to WT, indicating a possible PGC-1α mediated regulation of TNFα. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFα expression in these mice. Systemically, TG mice had reduced basal plasma TNFα levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFα levels as WT and showed more marked induction in plasma TNFα than WT after LPS injection, MKO PGC-1α mice had a reduced plasma TNFα and skeletal muscle TNFα mRNA response to LPS. In conclusion, the present findings suggest that PGC-1α enhances basal TNFα expression in skeletal muscle and indicate that PGC-1α does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1α seems however to impair the acute TNFα response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients.