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OBJECTIVE: To investigate the effect of electroacupuncture (EA) plus treadmill exercise on the expression of peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α), Irisin, AMP-activated protein kinase (AMPK) in skeletal muscle of diet-induced obesity (DIO) rats, so as to explore its mechanism underlying body reduction promotion. METHODS: Forty-two male SD rats were divided into normal diet (control, n＝10), high fat diet (model), EA, treadmill exercise and EA plus treadmill exercise (combination) groups (n＝8 in each of the latter 4 groups). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times per week for a total of 8 weeks. Rats of the treadmill exercise group were forced to perform exercise on a treadmill (16 m/min) for 30 min, 5 times per week for a total of 8 weeks. Rats in the combination group received the above-mentioned two methods. During the treatment, rats in the control group were fed with normal fodder, rats in other groups were fed with high fat fodder, and their body weight was measured once a week. The expression levels of PGC-1α， fibronectin type Ⅲ domain containing 5 (FNDC5), AMPK mRNA and protein of skeletal muscle were measured by quantitative real-time PCR and Western blot，respectively. RESULTS: After modeling, the body weight was significantly increased (P<0.05), and the expression levels of PGC-1α and FNDC5 mRNA and protein, AMPK mRNA and phosphorylated AMPK (p-AMPK) protein in the skeletal muscle were considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the body weight was significantly down-regulated, while the expression levels of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA and p-AMPK protein were obviously up-regulated in the EA, treadmill exercise and combination groups relevant to the model group (P<0.05). The therapeutic effect of EA plus treadmill exercise was significantly superior to those of both simple EA and simple treadmill exercise in down-regulating the body weight, as well as in up-regulating the expression of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA, and p-AMPK protein (P<0.05). CONCLUSION: Both EA and treadmill exercise can significantly increase the expression of PGC-1α， FNDC5 and p-AMPK in skeletal muscle of DIO rats, suggesting their efficacy in restoring fatty acid oxidation in skeletal muscle cells and improving mitochondrial function, which may contribute to their function in body reduction. The therapeutic effect of EA plus treadmill exercise is better than that of simple EA and simple treadmill exercise.
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Objective To explore the mechanism of phlegm-resolving and stasis- removing herbals on NAFLD by observing expressions of PGC1α mRNA and insulin resistance. Methods A total of 60 male SD rats were randomly divided into the normal group, model group, positive medication control group, high-dose, middle-dose and low-dose group. The rats were fed with high-fat forage for 8 weeks. The positive medication control group were gavaged with Dongbao-Gantai liquid (0.9 g/kg/day), the high-dose, middle-dose and low-dose group were gavaged with Xiaotan-Huayu liquid (43.34、32.50、21.67 g/kg/day), and normal group, model group were gavaged with equal volume of distilled water. The drugs were given by 1 ml/100 g and last for 8 weeks. The levels of TC, TG, FFA, ALT, AST, FBG, FINS, and HOMA-IR in serum, and levels of TC, TG, and PGC-1α mRNA and pathological morphological changes in hepatic tissue were observed after 8 weeks. Results The levels of TG (0.55 ± 0.10 mmol/L, 0.58 ± 0.09 mmol/L, 0.67 ± 0.11 mmol/L vs. 1.18 ± 0.15 mmol/L), TC (1.48 ± 0.24 mmol/L, 1.69 ± 0.27 mmol/L, 1.74 ± 0.27 mmol/L vs. 3.29 ± 0.26 mmol/L), FFA (251.08 ± 48.18 μmol/L, 277.53 ± 56.73 μmol/L, 291.82 ± 48.67 μmol/L vs. 432.19 ± 67.83 μmol/L), ALT (29.32 ± 4.17 U/L, 31.26 ± 4.74 U/L, 33.56 ± 5.18 U/L vs. 47.21 ± 8.67 U/L), AST (11.05 ± 2.18 U/L, 12.15 ± 2.67 U/L, 12.96 ± 2.93 U/L vs. 19.43 ± 3.68 U/L), FBG (5.68 ± 1.22 mmol/L, 6.86 ± 1.36 mmol/L, 7.94 ± 1.82 mmol/L vs. 11.88 ± 2.54 mmol/L), FINS (8.48 ± 1.22 mmol/L, 9.55 ± 1.95 mmol/L, 9.96 ± 1.74 mmol/L vs. 12.96 ± 2.67 mmol/L), HOMA-IR (1.91 ± 0.26, 2.91 ± 0.65, 3.52 ± 0.58 vs. 6.89 ± 1.21) in serum of high-dose, middle-dose and low-dose groups were decreased than model group. Levels of FFA (242.19 ± 35.13 μmol/L, 259.78 ± 29.33 μmol/L, 277.62 ± 34.29 μmol/L vs. 436.48 ± 52.15 μmol/L), TG (23.65 ± 3.28 mmol/L, 24.41 ± 3.15 mmol/L, 25.37 ± 3.59 mmol/L vs. 15.98 ± 2.37 mmol/L), TC (7.15 ± 0.82 mmol/L, 8.60 ± 0.95 mmol/L, 8.86 ± 1.04 mmol/L vs. 36.98 ± 4.28 mmol/L) were in hepatic tissue of high-dose, middle-dose and low-dose groups were significantly lower than the model group. The levels of PGC-1α mRNA (1.24 ± 0.06, 1.02 ± 0.07, 0.99 ± 0.08 vs. 0.43 ± 0.06) in hepatic tissue of high-dose, middle-dose and low-dose groups were significantly higher than model group. Conclusions The phlegm-resolving and stasis-removing herbals may improve lipid metabolism by regulating the expression of PGC-1α mRNA, inhibiting gluconeogenesis and liver sugar output, correcting disturbance of lipid metabolism and improving insulin resistance.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activities of peroxisome proliferator-activated receptor gamma coactivator-1 alpha/uncoupling protein-1 (PGC-1 α/UCP-1) signaling pathway in white adipose tissue(WAT)of diet-induced obesity (DIO) rats, so as to reveal its underlying mechanism in body weight loss. METHODS: Thirty-four male Wistar rats were randomly divided into normal diet (control, n＝10), high fat diet (model), sham EA-acupoint and EA groups (n＝8 in each of the latter 3 groups). The obesity model was established by feeding the rats with high fat diet containing lard oil, sugar, albumen powder, cholesterol, salt and sodium cholate for 12 weeks. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36) and "Tianshu" (ST 25) or sham acupoints (about 5 mm beside ST 36 and ST 25) for 30 min, once daily, 5 times per week for a total of 8 weeks. During the treatment, all rats were fed with normal diet, and their body weight and length were measured once a week for calculating the Lee's index. The contents of serum total cholesterol (TC) and triglyceride (TG) were measured by using biochemical methods. The immunoactivity of PGC-1 α and UCP-1 in the abdominal WAT was detected by immunohistochemistry. RESULTS: After modeling, the Lee's index, serum TC and TG contents were significantly increased, and the levels of serum HDL-C, and PGC-1 α and UCP-1 immunoactivity in WAT considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the Lee's index, TC and TG contents were significantly down-regulated while HDL-C and PGC-1 α and UCP-1 immunoactivity were obviously up-regulated in the EA-acupoint group relevant to the model group (P<0.05). CONCLUSION: EA can effectively reduce the body weight and adipose content in obesity rats, which may be closely related to its effect in up-regulating PGC-1 α/UCP-1 signaling in WAT, suggesting an efficacy of EA in promoting the browning of WAT.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36) on mitochondrial oxidative stress of skeletal muscle in rats with chronic fatigue syndrome (CFS) based on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/ peroxlsome proliferator-activated receptor-γ coactivator-1 α (PGC-1 α) signaling, in order to reveal its mechanism underlying improvement of CFS. METHODS: Forty SD rats were randomly divided into normal control, CFS model, EA-Zusanli (ST 36) and EA-non-acupoint groups (n=10 rats in each group). The CFS model was established by forced exhausted load-bearing swimming (twice daily), chronic constraint (1 h) and sleep deprivation (20 h/day) for 14 days. Following modeling, EA (2 Hz/100 Hz, 2 V) was applied to bilateral Zusanli (ST 36) or non-acupoint (about 10-15 mm superior to the bilateral Iliac creast and about 20 mm lateral to the posterior median line) for 20 min, once a day for 10 days. The expression levels of ATP synthase, AMPK, phosphorylated (p)-AMPK, silent mating type information regulation 2 homolog-1 (SIRT 1) and PGC-1 α proteins, and ATP synthase, SIRT 1 and PGC-1 α mRNAs of the quadriceps femoris muscle were detected by Western blot and fluorescence quantitative PCR, respectively. The rats' grabbing force was detected by using a grabbing-force detector. RESULTS: Compared with the normal group, the grabbing force, and the expression levels of ATP synthase and PGC-1 α proteins and mRNAs were significantly decreased (P<0.05, P<0.01), while the expression of SIRT 1 protein was significantly up-regulated (P<0.05) in the CFS model group. Following EA intervention, the grabbing force and the expression levels of ATP synthase mRNA, SIRT 1 and PGC-1 α proteins and mRNAs, and p-AMPK/AMPK were significantly up-regulated in the EA-Zusanli (ST 36) group (P<0.05, P<0.01). CONCLUSION: EA of ST 36 can raise the grabbing force of CFS rats, which may be related to its effects in up-regulating the expression of ATP synthase mRNA, SIRT 1 and PGC-1 α proteins and mRNAs, and p-AMPK/AMPK to reduce mitochondrial oxidative stress reaction and in increasing ATP synthesis.
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Objective To investigate the role of SIRT1/PGC-1α pathway in the auditory cortex aging of guinea pigs with age-related hearing loss and whether the electroacupuncture can delay aging process of the auditory cortex in the aged guinea pigs induced by D-galactose through the regulation of SIRT1/PGC-1α pathway.Methods Thirty 4-month-old guinea pigs were randomly divided into three groups including the control group (n=10),D-galactose group (model group,n =10),and D-galactose and electroacupuncture group (electroacupuncture group,n =10).The elderly group (n=10) was composed of 18-month-old guinea pigs.The guinea pigs in model group and electroacupuncture group had been subcutaneously injected with D-galactose(300 mg· kg-1· d-1)for 6 weeks.Moreover,the guinea pigs in electroacupuncture group electroacupunctured at Tinggong and Yifeng for 15 minutes half an hour later once a day.After 6 weeks,the ABR threshold of guinea pigs in each group was detected.The mRNA and protein expression of SIR1 and PG-C-1α in auditory cortex of guinea pigs were detected by real -time fluoreacence quantitative PCR and Western Blot.Results There was a significant increase in the ABR threshold of the model group and elderly group (P＜0.001,compared with the control group),decrease in the electroacupuncture group (P＜0.001,compared with the model group),and no significant difference between model group and elderly group(P＞0.05).There was significant decrease in the expression of SIRT1 and PGC-1α in the model groupand elderly group(P＜0.05,compared with the control group),and significant increase at mRNA and protein levels in the electroacupuncture group (P＜0.05,compared with the model group).Conclusion SIRT1/PG-C-1α pathway may play a role in aging process of the auditory cortex in the aged guinea pigs induced by D-galactose,and electroacupuncture at Tinggong and Yifeng may increase the antioxidant capacity of auditory cortex by activating SIRT1/PGC 1α in guinea pigs with age-related hearing loss,thus delaying the aging process of auditory cortex.
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The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1 (AMPKα1) and peroxisome proliferator-activated receptor 1α (PGC-1α). Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3 were decreased (P < 0.05) in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.
Subject(s)
Animals , AMP-Activated Protein Kinases , Metabolism , Adenosine Triphosphate , Metabolism , Aorta , Metabolism , Cardiovascular Diseases , Metabolism , Caspase 3 , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Diptera , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Endothelial Cells , Metabolism , Endothelium, Vascular , Metabolism , Energy Metabolism , Leeches , Mitochondria , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Metabolism , Phytotherapy , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Prunus persica , Rats, Sprague-Dawley , Rheum , Signal TransductionABSTRACT
Objective To observe the effects of sports with different strength combined with traditional Chinese medicine on expression of PGC-1α and function of vascular endothelium of IGT rats; To discuss the synergistic action and its mechanism.Methods Seventy healthy male SD rats were randomly divided into blank group (10 rats), which were given regular diet, and the other 60 rats were given high-glucose and high-lipoid diet to establish the IGT model rats, which were then randomly divided into 5 groups, including IGT model group (model group), simple Chinese medicine group (Chinese medicine group), low strength sports+Chinese medicine (low strength group), middle strength+Chinese medicine (middle strength group), and high strength sports+Chinese medicine groups (high strength group), 10 rats in each group. Rats in blank group, model group and Chinese medicine group exercised freely. While rats in different sport strength groups conducted treadmill exercise with different strength, and were givenDanzhi Jiangtang Capsules for gavage. Changes of NO, eNOS, vWF and EMP before and after the treatment were compared, the PGC-1α level was detected.Results Compared with the blank group, levels of NO, eNOS and PGC-1α decreased, while the levels of vWF and EMP increased in model group (P<0.05). Compared with the model group, levels of NO, eNOS and PGC-1α increased in all treatment groups, while the levels of vWF and EMP decreased (P<0.05,P<0.01). Conclusion Middle strength sports combined withDanzhi Jiangtang Capsules may effectively improve function of vascular endothelium.
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The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P < 0.05), including blood glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and insulin. Our further results also indicated that oral BF administration increased the expression of PGC-1α and UCP1 in BAT. Moreover, BF also reduced the expression of inflammatory cytokines in WAT, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These findings suggested that the mechanism of BF against obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.