Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes

Abstract

The aim of the present study was to investigate changes in intramuscular triglyceride (IMTG) content and perilipin 2 expression in skeletal muscle tissue following 6 mo of endurance-type exercise training in type 2 diabetes patients. Ten obese male type 2 diabetes patients (age 62 ± 1 yr, body mass index BMI 31 ± 1 kg/m²) completed three exercise sessions/week consisting of 40 min of continuous endurance-type exercise at 75% V(O₂ peak) for a period of 6 mo. Muscle biopsies collected at baseline and after 2 and 6 mo of intervention were analyzed for IMTG content and perilipin 2 expression using fiber type-specific immunofluorescence microscopy. Endurance-type exercise training reduced trunk body fat by 6 ± 2% and increased whole body oxygen uptake capacity by 13 ± 7% (P < 0.05). IMTG content increased twofold in response to the 6 mo of exercise training in both type I and type II muscle fibers (P < 0.05). A threefold increase in perilipin 2 expression was observed from baseline to 2 and 6 mo of intervention in the type I muscle fibers only (1.1 ± 0.3, 3.4 ± 0.6, and 3.6 ± 0.6% of fibers stained, respectively, P < 0.05). Exercise training induced a 1.6-fold increase in mitochondrial content after 6 mo of training in both type I and type II muscle fibers (P < 0.05). In conclusion, this is the first study to report that prolonged endurance-type exercise training increases the expression of perilipin 2 alongside increases in IMTG content in a type I muscle fiber-type specific manner in type 2 diabetes patients.

Fig. 1.

Fiber-type specific cytochrome c oxidase (COX) expression. A: mean fiber type-specific COX expression (expressed as %fiber area stained) at baseline and following 2 and 6 mo of exercise training. Data represent means ± SE. Time effect, P = 0.006; fiber effect, P < 0.001; interaction of time and fiber, P = 0.112. *Significant effect of time; †significant difference between fiber types (P < 0.05). B, top: representative images of mitochondrial network, stained with anti-COX and viewed and quantified with confocal immunofluorescence microscopy. Scale bar, 40 μm. B, bottom: representative images of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria areas. Scale bar, 1 μm.

Fig. 2.

Fiber type-specific intramuscular triglyceride (IMTG) content and perilipin 2 expression. Mean fiber type-specific perilipin 2 expression (A) and IMTG content (B) at baseline and following 2 and 6 mo of exercise training (expressed as %fiber area stained). Data represent means ± SE. A: time effect, P = 0.001; fiber effect, P < 0.001; interaction of time and fiber, P = 0.003. B: time effect, P = 0.017; fiber effect, P < 0.001; interaction of time and fiber, P = 0.01. *Significant effect of time; †significant difference between fiber types; #significant difference from baseline (P < 0.05).

Fig. 3.

Immunofluorescence images of fiber type-specific perilipin 2 protein expression. A: representative images of perilipin 2 at baseline and 6 mo, stained using anti-perilipin 2 in combination with anti-myosin heavy chain type I and wheat germ agglutinin 350 (WGA350) and viewed and quantified with wide-field immunofluorescence microscopy. Scale bar, 50 μm. B: representative confocal images of perilipin 2 at baseline and 6 mo; rings of perilipin staining are clearly visible in both images. Scale bar, 10 μm.