Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance

Abstract

BackgroundInsulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the vastus lateralis muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention.ResultsExercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the vastus lateralis muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO2max value and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group.ConclusionThe 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.

Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

“…Both studies have been described in detail elsewhere [18, 21]. The study protocol [18] was briefly as follows.…”

Mitochondrial dynamics, quality control and miRNA regulation in skeletal muscle: implications for obesity and related metabolic disease

“…Furthermore, mitochondrial HSP60 and GRP75 (a HSP70 family member) protein expression were shown to increase significantly in vastus lateralis muscle upon a 2-year lifestyle (diet + exercise) intervention in a large group of middle-aged obese subjects with impaired glucose tolerance, whereas cytosolic heat shock proteins such as HSP72 or HSP90 remained unchanged [38]. Additionally, a positive correlation was observed between the increase in HSP60 and the increase in oxygen radical absorbing capacity (ORAC) values, indicating a possible connection between mitochondrial protein quality control and antioxidant capacity [38].…”

“…Additionally, a positive correlation was observed between the increase in HSP60 and the increase in oxygen radical absorbing capacity (ORAC) values, indicating a possible connection between mitochondrial protein quality control and antioxidant capacity [38].…”

Mitochondrial stress: A bridge between mitochondrial dysfunction and metabolic diseases?

“…A preliminary epidemiological study demonstrates that lower blood HSP60 level is associated with increased risk of type 2 diabetes [67]. Exercise training with dietary counseling increases mitochondrial HSP60 and glucose-regulated protein 75 (GRP75) expression in skeletal muscle in middle-aged subjects with impaired glucose tolerance [68], suggesting a protective role of HSP60, or possibly the UPR mt in glucose metabolism and antioxidative capacity. In addition to metabolic dysregulation, mitochondrial stress and/or impairment in the UPR mt pathway such as reducing the expression levels or activities of mitochondrial chaperones has also been implicated in neurological diseases and sporadic diseases of aging [32, 69–71].…”