Lower capillary density but no difference in VEGF expression in obese vs. lean young skeletal muscle in humans

Abstract

Obesity is associated with lower skeletal muscle capillarization and lower insulin sensitivity. Vascular endothelial growth factor (VEGF) is important for the maintenance of the skeletal muscle capillaries. To investigate whether VEGF and VEGF receptor [kinase insert domain-containing receptor (KDR) and Flt-1] expression are lower with obesity, vastus lateralis muscle biopsies were obtained from eight obese and eight lean young sedentary men before and 2 h after a 1-h submaximal aerobic exercise bout for the measurement of VEGF, KDR, Flt-1, and skeletal muscle fiber and capillary characteristics. There were no differences in VEGF or VEGF receptor mRNA at rest between lean and obese muscle. Exercise increased VEGF (10-fold), KDR (3-fold), and Flt-1 (5-fold) mRNA independent of group. There were no differences in VEGF, KDR, or Flt-1 protein between groups. Compared with lean skeletal muscle, the number of capillary contacts per fiber was the same, but lower capillary density (CD), greater muscle cross sectional area, and lower capillary-to-fiber area ratio were observed in both type I and II fibers in obese muscle. Multiple linear regression revealed that 49% of the variance in insulin sensitivity (homeostasis model assessment) could be explained by percentage of body fat (35%) and maximal oxygen uptake per kilogram of fat-free mass (14%). Linear regression revealed significant relationships between maximal oxygen uptake and both CD and capillary-to-fiber perimeter exchange. Although differences may exist in CD and capillary-to-fiber area ratio between lean and obese skeletal muscle, the present results provide evidence that VEGF and VEGF receptor expression are not different between lean and obese muscle.

Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

“…Similar findings were previously reported for Biceps muscles of Yucatan swine on a "Western"-type diet (14). These data correlate well with previous studies in humans showing that skeletal muscles from obese compared with lean individuals have greater muscle CSAs (9,24). The increased CSAs could have a negative effect on the oxygen and substrate supply to the center of the fiber, leading to the reduced muscle performance.…”

“…Increased fiber size could diminish oxygen and substrate supply for the metabolic processes in the central area of the fiber. Skeletal muscles from obese compared with lean individuals had greater muscle cross-sectional areas (CSAs) of both type 1 and 2 fibers (9,24). Weight loss resulted in a 14 -25% decrease of the fiber CSAs of both type 1 and type 2 muscle fibers (12), supporting the idea that obesity correlates with an increase in muscle fiber area.…”

Opposing Effects of Reduced Kidney Mass on Liver and Skeletal Muscle Insulin Sensitivity in Obese Mice

“…Capillary rarefaction was previously associated with insulin resistance both in humans and rodents (19)(20)(21). In accordance with our findings presented herein, Flisi nski et al (43) reported reduced numbers of capillaries as well as a decreased capillary-tofiber ratio in gastrocnemius and longissimus muscle in UniNx male Wistar rats.…”

“…Accordingly, the number of capillaries perfusing the muscle is positively related to peripheral insulin action (14). Moreover, reduced blood flow to the muscle is correlated with insulin resistance (15)(16)(17)(18), and insulin-resistant humans and rodents exhibit capillary rarefaction (19)(20)(21). However, it still remains unclear whether the reduction in capillaries is a cause or consequence of muscle insulin resistance (22).…”

Excessive secretion of IL-8 by skeletal muscle in type 2 diabetes impairs tube growth: potential role of PI3K and the Tie2 receptor

“…Crucial features of T2D are insulin resistance and impaired glucose disposal in muscle (11). Importantly, skeletal muscle capillaries mediate the supply of oxygen, substrates, hormones, and inflammatory cells from the circulation (20). Inadequate capillarization of skeletal muscle (SkM) may lead to relative hypoxia and an inflammatory response as well as decreased metabolism.…”