The Changes Of Hydrogen Sulfide Content And Myokines In Rat Skeletal Muscle During Weight Loss Induced By Exercise

Background: Currently, obesity has become a major public health problem that affects social development and individual health. For people today, nutrition excess and physical inactivity are the key factors cause or worsen obesity, so the exercise plays an irreplaceable role in the prevention and control of obesity.Skeletal muscle is not only the main organ involved in movement, but also has an important endocrine function. With the contraction of skeletal muscle, a variety of cytokines can be secreted, some of which not only play roles in local field, but also can be secreted into the blood and into other tissues and organs playing different physiological functions, and these cytokines are also known as myokines.IL-6 was the first discovered myokine, its relationship with energy metabolism and exercise has a lot of reports. However, these studies were conducted in normal healthy state, the regulation of exercise to IL-6 under pathological conditions, such as obese state, has not be researched.IL-15 is a new myokine that is mainly secreted by skeletal muscle which can promote the accumulation of myoprotein and resist its decomposition. In addition, IL-15 acts on IL-15 receptor of adipose tissue thereby regulating the metabolism of fat, so that has a positive effect on the treatment of obesity and skeletal muscle atrophy. Interestingly, exercise also plays an important role in prevention of obesity and skeletal muscle atrophy whose mechanism is related to IL-15 or not, is unclear.Hydrogen sulfide(H2S) is a recently discovered gas molecule neurotransmitters, its diverse roles in regulating metabolism, inflammation, nerve and blood vessels have attracted an increasing number of studies. A recent study showed that exogenous H2 S can improve lipid metabolism and mitigate the fatty liver. It is also reported that three enzymes which can catalyze the generation of endogenous H2 S were all expressed in rat skeletal muscle, however, the effects of exercise on skeletal muscle endogenous H2 S synthesis system has not been reported.Objective: Detect the endogenous H2 S synthesis system and IL-6, IL-15 gene expression changes in the skeletal muscle of rat during weight loss induced by exercise. Provide information for in-depth understanding of the mechanisms of exercise to lose weight and the role of H2 S in weight loss induced by exercise.Methods: SD male rats are the main study object, feeding the rats on high-fat diet for eight weeks to establish obese rat model with the intervention of moderate intensity treadmill exercise. This study consisted of four groups: normal control group(CN), obese group(OB), obesity plus exercise group(OB+EX). Detected the H2 S content in rat skeletal muscle by enzyme-linked immunosorbent assay(ELISA); Detected H2 S synthesis enzymes cystathionine γ cleavage enzyme(CSE), cystathionine β synthase(CBS) and 3-mercaptopropionic pyruvate-transferase enzyme(MST) m RNA and protein expression by RT-PCR, Real-time PCR and Western blotting assay; conform the CSE Positioning and protein expression in rat skeletal muscle by immunohistochemistry(IHC) test; detected IL-6, IL-15 m RNA expression in skeletal muscle by RT-PCR.Results: ELISA results showed that: Compared with the CN group, the H2 S content of rat skeletal muscle in OB group was significantly lower(P <0.01); compared with the OB group, the H2 S content of rat skeletal muscle in OB+EX group was increased(P <0.01).Real-time PCR results showed that: Compared with the CN group, CSE gene m RNA expression levels of rat skeletal muscle in OB group decreased significantly(P <0.01), m RNA expression of CBS gene also decreased(P <0.01); and compared OB group, CSE gene m RNA expression levels of rat skeletal muscle in OB+EX group increased(P <0.05).Western blotting results showed that: Compared with the CN group, the protein expression levels of CSE gene in rat skeletal muscle in OB group significantly decreased(P <0.01); compared with OB group, the protein expression levels of CSE gene in rat skeletal muscle in OB+EX group significantly increased(P <0.01).IHC results showed that CSE protein was mainly localized in the cytoplasm in rat skeletal muscle, compared with control group, CSE protein expression levels in exercise group significantly increased.RT-PCR results showed that: Compared with the CN group, m RNA expression of IL-6 gene in rat skeletal muscle in OB group was significantly higher(P <0.01), m RNA expression levels of IL-15 did not change; compared with the OB group, m RNA expression levels of IL-6 gene in rat skeletal muscle in OB+EX group is reduced(P <0.05), the m RNA expression of IL-15 gene is no different.Conclusions:1. Obesity can lead to the decrease of H2 S content in rat skeletal muscle, while moderate-intensity exercise will make it rise, which may be related to the regular changes of the CSE that is one of the endogenous H2 S synthesis enzyme.2. Obesity can increase IL-6 m RNA expression in rat skeletal muscle, while moderate-intensity exercise can lower it, which may be associated with increased H2 S content induced by exercise in skeletal muscle.