Abstract
This study investigated whether glutamine (GLN) pretreatment can enhance circulating endothelial progenitor cells (EPCs) and attenuate inflammatory reaction in high-fat diet-induced obese mice with limb ischemia. Mice were assigned to a normal control (NC), high-fat control (HC), limb ischemia (HI), and GLN limb ischemia (HG) groups. The NC group provided chow diet and treated as a negative control. Mice in the HC and HI groups were fed a high-fat diet which 60% energy provided by fat for 8 weeks. Mice in the HG group were fed the same diet for 4 weeks and then transferred to a high-fat diet with 25% of total protein nitrogen provided as GLN to replace part of the casein for the subsequent 4 weeks. After feeding 8 weeks, mice in the HC group were sham-operated, while the HI and HG groups underwent an operation to induce limb ischemia. All mice except the NC group were euthanized on either day 1 or 7 after the operation. The results showed that the 8 weeks' high-fat diet feeding resulted in obesity. The HG group had higher circulating EPCs on day 1 while muscle vascular endothelial growth factor, matrix metalloproteinase-9, and hypoxia-inducible factor-1 gene expressions were higher on day 7 postischemia than those of the HI group. The superoxide dismutase activity and reduced glutathione content in affected muscles were higher, whereas mRNA expressions of interleukin-6 and tumor necrosis factor-α were lower in the HG than those in the HI group. These findings suggest that obese mice pretreated with GLN-supplemented high-fat diet increased circulating EPC percentage, enhanced the antioxidant capacity, and attenuated inflammatory reactions in response to limb ischemia.
Highlights
Obesity, a complex multifaceted condition, has become an important worldwide health problem
All data are representative of duplicate measurements on day 1 or 7 (n = 8 for the respective groups)
Differences among groups were analyzed by a one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. ∗Significant differences from the two other groups. +Significant differences from the high-fat control (HC) group. #Significant differences from the HI group at the same time point (p < 0:05)
Summary
A complex multifaceted condition, has become an important worldwide health problem. Excessive accumulation of adipose tissues was shown to be associated with inflammation in metabolic tissues, called “meta-inflammation,” which may result in chronic low-grade inflammation and modest increases in circulating proinflammatory mediators [1]. Metainflammation is characterized by an impaired vascular structure and function in tissues and organs [2]. Obesity has been shown to be a predictor of cardiovascular diseases [3], and body mass index is positively associated with peripheral artery disease (PAD) [4]. Critical limb ischemia is a severe form of PAD. Lower-limb ischemia can cause claudication that eventually may lead to amputation [5]. Obese subjects demonstrated 3-5 times higher risk of PAD with limb ischemia [4]
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