Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.

Effect characteristics of electroacupuncture at the acupoints of different regions in regulating gastric motility of the rats: response time. / ç”µé’ˆä¸åŒéƒ¨ä½è §ç©´è°ƒèŠ‚å¤§é¼ èƒƒè¿åŠ¨æ•ˆåº”ç‰¹å¾ç ”ç©¶ï¼šå“åº”æ—¶é—´.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Zhongwan" (CV 12) and "Zusanli" (ST 36) on gastric motility and explore the response time of the acupoints at different regions for regulating gastric motility and its neuromechanism. METHODS: Thirty-three SD rats were randomly divided into a normal group, a vagectomy group and a splanchnicotomy group, 11 rats in each one. Vagectomy and splanchnicotomy were operated in the rats of the vagectomy group and the splanchnicotomy group, respectively. In each group, EA was delivered at "Zhongwan" (CV 2) and "Zusanli"(ST 36) on the left successively (with disperse-dense wave, 2 Hz/15 Hz in frequency and 2 mA in intensity); and it was performed at one acupoint for 1 min. Using multiple physiological signal collecting system, the intragastric pressure was measured 1 min before EA and in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA in the rats of each group, separately. The change rate of intragastric pressure was calculated to compare the effect size among groups. RESULTS: 1) Compared with that before intervention, in the normal group, the intragastric pressure was dropped in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12) (P<0.01); and it was elevated in 0 s to 60 s and 30 s to 60 s of EA at "Zusanli" (ST 36) (P<0.01). 2) In 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12), the intragastric pressure decreased when compared with that before intervention in both the vagectomy group and the splanchnicotomy group (P<0.01, P<0.05); and it increased in 0 s to 60 s, 0 s to 30 s and 30 s to 60 s of EA at "Zusanli" (ST 36) in the splanchnicotomy group (P<0.05). 3) Compared with the normal group, the inhibition effect size was reduced in 30 s to 60 s of EA at "Zhongwan" (CV 12) in the vagectomy group (P<0.01), and in 0 s to 30 s and 30 s to 60 s of EA at "Zhongwan" (CV 12) in the splanchnicotomy group (P<0.01). During EA at "Zhongwan" (CV 12) for 0 s to 30 s and 30 s to 60 s, the inhibition effect size was declined more obviously in the splanchnicotomy group when compared with that in the vagectomy group (P<0.01). The excitation effect size was dropped in the vagectomy group when EA at "Zusanli" (ST 36) for 30 s to 60 s compared with the normal group (P<0.01), while it increased during 0 s to 30 s in the splanchnicotomy group (P<0.05). Compared with that of the vagectomy group, the excitation effect size increased more remarkably in the splanchnicotomy group when EA at "Zusanli" (ST 36) for 0 s to 30 s and 30 s to 60 s (P<0.01). CONCLUSIONS: Electroacupuncture at the acupoints of different regions differ in the response time and neuromechanism for regulating gastric motility of normal rats. The response time at "Zhongwan" (CV 12) is short and the effect of this acupoint works fast within 30 s; while that at "Zusanli" (ST 36) is prolonged and the effect starts 30 s later. In 0 s to 30 s of EA, the effect of "Zhongwan" (CV 12) and "Zusanli" (ST 36) is predominated by the splanchnic nerve; and in 30 s to 60 s, the effect of "Zhongwan" (CV 12) may be co-innervated by the splanchnic nerve and the vagus nerve, and that of "Zusanli" (ST 36) only by the vagus nerve.

Electroacupuncture stimulation ameliorates cognitive impairment induced by long-term high-fat diet by regulating microglial BDNF.

Long-term high-fat diet (HFD) in adolescents leads to impaired hippocampal function and increases the risk of cognitive impairment. Studies have shown that HFD activates hippocampal microglia and induces hippocampal inflammation, which is an important factor for cognitive impairment. Electroacupuncture stimulation (ES), a nerve stimulation therapy, is anti-inflammatory. This study explored its therapeutic potential and mechanism of action in obesity-related cognitive impairment. 4-week-old C57 mice were given either normal or HFD for 22 weeks. At 19 weeks, some of the HFD mice were treated with ES and nigericin sodium salt. The cognitive behavior was assessed through Morris water maze test at 23 weeks. Western blotting was used to detect the expression levels of pro-inflammatory molecules IL-1ß and IL-1R, synaptic plasticity related proteins synaptophysin and Postsynaptic Density-95 (PSD-95), and apoptotic molecules (Caspase-3 and Bcl-2), in the hippocampus. The number, morphology, and status of microglia, along with the brain-derived neurotrophic factor（BDNF） content, were analyzed using immunofluorescence. ES treatment improved cognitive deficits in HFD model mice, and decreased the expressions of microglial activation marker, CD68, and microglial BDNF. Inhibition of proinflammatory cytokine, IL-1ß, and IL-1R promoted PSD-95 and synaptophysin expressions. Peripheral NLRP3 inflammasome agonist injections exacerbated the cognitive deficits in HFD mice and promoted the expressions of IL-1ß and IL-1R in the hippocampus. The microglia showed obvious morphological damage and apoptosis. Collectively, our findings suggest that ES inhibits inflammation, regulates microglial BDNF, and causes remodeling of hippocampal function in mice to counteract obesity-like induced cognitive impairment. Overexcitation of peripheral inflammasome complexes induces hippocampal microglia apoptosis, which hinders the effects of ES.

Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol.

INTRODUCTION: Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. METHODS AND ANALYSIS: A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2 test and I2 statistic will be used for assessing heterogeneity between studies. ETHICS AND DISSEMINATION: No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. PROSPERO REGISTRATION NUMBER: CRD42022384348.

Neuromechanical Dimorphism of Hypoglycemic Effect of Electroacupuncture.

INTRODUCTION: Electroacupuncture (EA) has a favorable impact on blood glucose stability. Blood glucose homeostasis is linked to sexual dimorphism. The majority of research has, however, focused on male participants, and sex differences have not been adequately taken into account. METHODS: Here, we investigated how EA intervention affected pancreatic metabolic stress and explored if there were any sex-related changes in the maintenance of pancreatic function following intraperitoneal injection of a 10 g/kg glucose solution. RESULTS: The transient receptor potential vanilloid 1 (TRPV1) calcitonin gene-related peptide (CGRP)-ß cell pathway of the male pancreas is vital to maintain glucose metabolism in mice. In contrast, there is a sex bias in TRPV1, which implies that female mice have additional routes for preserving glucose homeostasis. EA is ineffective on Trpv1-/- male mice. It also revealed that TRPV1 in male mice served as a crucial mediator for the EA control of blood glucose. Meanwhile, the sympathetic marker tyrosine hydroxylase showed higher expression in the male pancreas, while the cholinergic marker choline acetyltransferase is expressed predominantly in female mice. Injecting γ-aminobutyric acid into the paraventricular nucleus of male mice caused a disruption in blood glucose and a lack of response to EA. It verified that male mice had a more pronounced sympathetic innervation of the pancreas than female mice. CONCLUSION: Our research has demonstrated that the TRPV1 sensory afferent nerve and sympathetic efferent nerve are capable of maintaining glucose homeostasis, exhibiting a distinct sexual dimorphism. Furthermore, this regulation is contingent on the EA effect.

[Mechanism and protocol optimization of acupuncture in treatment of obesity based on sympathetic nerve system].

The physiological function of adipose tissue is dominated by the sympathetic nerve system (SNS), but obesity and other diseases may cause the abnormality of the SNS signaling pathway. Acupuncture has been proved to be an effective the-rapy to improve the function of SNS in adipose tissue. Based on the physiological and pathological significance of SNS, this paper reviewed the molecular pathways in which acupuncture directly or indirectly regulated the function of SNS in adipose tissue. As the mechanism of electroacupuncture in regulating autonomic nerves was continuously illuminated, the adjustment of acupuncture mode, such as selection of acupoints in different nerve segments and adjustment of stimulation parameters of electroacupuncture, presumedly induced different content ratios of neurotransmitters released by SNS efferent axons, including noradrenaline and neuropeptide Y, thereby producing different effects on weight loss. Therefore, the specific connections between various acupuncture modes and neurotransmitters released by SNS enriched the intrinsic nerve coding of acupoints, thus optimizing the acupoint selection protocol for the treatment of obesity.

Qingfei oral liquid alleviates RSV-induced lung inflammation by promoting fatty-acid-dependent M1/M2 macrophage polarization via the Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Respiratory syncytial virus (RSV) is a common pathogen that causes lower respiratory tract disease in infants and the elderly, and no vaccination is presently available. Qingfei oral liquid (QF), a traditional Chinese medicine formula, has been shown in clinic to have anti-inflammatory properties. AIM OF THE STUDY: The present study investigated whether QF can suppress RSV-induced lung inflammation in mice models via fatty acid-dependent macrophage polarization. MATERIAL AND METHODS: BALB/c mice were given a low, medium, or high dose of QF intragastrically for four consecutive days following RSV infection. The lung inflammatory status was assessed using H&E staining and cytokine assays. The active components of QF and fatty acid metabolism were analyzed using ultra-high-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). A lipid metabolism-related pathway was found through network pharmacology and molecular docking investigations. Western blotting assays were used to determine the levels of ATP-citrate lyase (ACLY), peroxisome proliferation-activated receptor alpha (PPAR), Akt protein kinase B and its phosphorylated form in Akt signaling. Flow cytometry was used to quantify the number of macrophage subtypes (M1/M2), and immunohistochemistry was used to examine the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). RESULTS: In the lung tissues of RSV-infected mice, QF suppressed the transcription of pro-inflammatory proteins such as interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), while increasing the level of anti-inflammatory factors such as interleukin-10 (IL-10). The alterations in metabolic enzyme activity mediated by Akt signaling were linked to QF's significant reduction in lung fatty acid accumulation. Lower ACLY expression and higher PPAR expression were found after QF treatment, showing that these two enzymes were downstream targets of Akt signaling, controlling fatty acid synthesis (FAS) and fatty acid oxidation (FAO), respectively. The reprogramming of fatty acid metabolism resulted in the polarization of macrophages from M1 to M2, with lower expression of iNOS and higher expression of Arg-1. Additionally, application of an Akt agonist (SC-79) reduced QF's anti-inflammatory effects by increasing FAS and decreasing macrophage polarization. CONCLUSIONS: QF inhibited Akt-mediated FAS and polarized M1 to M2 macrophages, resulting in an anti-inflammatory impact.

Hypoglycemic Effect of Electroacupuncture at ST25 Through Neural Regulation of the Pancreatic Intrinsic Nervous System.

Electroacupuncture (EA) is considered to have potential antidiabetic effects; however, the role of the pancreatic intrinsic nervous system (PINS) in EA-induced amelioration of type 2 diabetes (T2DM) remains unclear. Therefore, we investigated whether EA at ST25 exerts any beneficial effects on insulin resistance (IR), inflammation severity, and pancreatic ß cell function via the PINS in a rat model of a high-fat diet-streptozotocin (HFD/STZ)-induced diabetes. To this end, Sprague Dawley rats were fed with HFD to induce IR, followed by STZ (35 mg/kg, i.p.) injection to establish the T2DM model. After hyperglycemia was confirmed as fasting glucose level > 16.7 mmol/L, the rats were treated with EA (2 mA, 2/15 Hz) for the next 28 days. Model rats showed increased serum glucose, insulin, IR, and TNF-α levels with a concomitant decrease in ß cell function. Microscopy examination of the pancreas revealed pathological changes in islets, which reverted to near-normal levels after EA at ST25. EA improved islet cell morphology by increasing islet area and reducing vacuolation. EA at ST25 decreased transient receptor potential vanilloid 1 (TRPV1) and increased substance P (SP) and calcitonin gene-related peptide (CGRP) expression. Subsequently, insulin secretion decreased and impaired pancreatic endocrine function was restored through the TRPV1 channel (SP/CGRP)-insulin circuit. EA increased choline acetyltransferase and neuropeptide Y expression and controlled inflammation. It also enhanced the cocaine and amphetamine-regulated transcript prepropeptide expression and promoted glucagon-like peptide-1 secretion. Additionally, the electrophysiological activity of PINS during acupuncture (2.71 ± 1.72 Hz) was significantly increased compared to the pre-acupuncture frequency (0.32 ± 0.37 Hz, P < 0.05). Thus, our study demonstrated the beneficial effect of EA on ß cell dysfunction via the PINS in rat models of HFD-STZ-induced T2DM.

Electroacupuncture at ST36 Improve the Gastric Motility by Affecting Neurotransmitters in the Enteric Nervous System in Type 2 Diabetic Rats.

Electroacupuncture (EA) can effectively relieve hyperglycemia and gastric emptying disorders in diabetic gastroparesis (DGP). However, the effect of EA on type 2 diabetes mellitus (T2DM) gastroparesis and its mechanism in the enteric nervous system (ENS) are rarely studied. We investigated the therapeutic effect of EA at ST36 and its effect on the main inhibitory and excitatory neurotransmitters in the ENS in DGP rats. Male Sprague-Dawley (SD) rats were fed a high-fat diet for 2 weeks and injected with streptozotocin (STZ) at 35 mg/kg to induce T2DM. T2DM rats were divided into the diabetic mellitus (DM) group and the EA group. The control (CON) group comprised normal rats without any intervention. EA treatment was started 6 weeks after the induction of DM and continued for 5 weeks. The body weight and food intake of the rats were recorded every week. Blood glucose, insulin, glucose tolerance, gastric emptying, and antral motility were measured after treatment. The expression of protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT) in gastric antrum were quantified by western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The T2DM gastroparesis model was successfully established. EA treatment reduced the body weight, food intake, and blood glucose; improved glucose intolerance and insulin resistance; increased the gastric emptying rate, the mean antral pressure, and the amplitude of antral motility; and decreased the frequency of antral motility compared with those in the DM group. EA treatment increased the expression level of nNOS, ChAT, and PGP9.5 proteins, and nNOS and ChAT mRNA. The results suggested that EA at ST36 could ameliorate DGP, partly restore the damage to general neurons, and increase nNOS and ChAT in the gastric antrum. EA improved DGP partly via reducing the loss of inhibitory and excitatory neurotransmitters in the ENS.

Electroacupuncture Stimulation Regulates Adipose Lipolysis via Catecholamine Signaling Mediated by NLRP3 Suppression in Obese Rats.

Chronic low-grade inflammation of visceral adipose tissue can cause obesity-associated insulin resistance, leading to metabolic syndrome. However, anti-inflammatory drugs and those for obesity management can lead to serious side effects such as abnormal heart rate and blood pressure. Consequently, this study aimed to explore the therapeutic potential of electroacupuncture stimulation (ES) for obesity and associated chronic inflammation. Sprague-Dawley male rats were fed a high-fat diet (HFD) for ten weeks to build an obesity model, and half of the diet-induced obesity (DIO) rats were received ES. The levels of inflammatory factors were detected by ELISA and qPCR analysis. The nerve-associated macrophages were marked with immunofluorescence staining. The molecular mechanism of NLRP3 inflammasome in ES was determined by the NLRP3 inflammasome activation model. Compared to HDF rats, ES showed decreased body weight and chronic inflammatory damage. Specifically, this occurred via a decrease in monoamine oxidase-A (MAOA) expression, which suppressed noradrenaline degradation. MAOA is expressed in nerve-associated macrophages (NAMs), and ES attenuated NAMs by suppressing the NLRP3 inflammasome. The NLRP3 agonist blocked the noradrenaline degradation-reducing effect of ES, and an increase in lipolysis via the inhibition of the NLRP3 inflammasome attenuated NAMs. Thus, our findings suggest that ES induced lipolysis via activation of the NLRP3 inflammasome in nerve-associated macrophages (NAMs), independently of sympathetic nervous system activity.

Role of Neuro-Immune Cross-Talk in the Anti-obesity Effect of Electro-Acupuncture.

There is evidence to show that electro-acupuncture (EA) has a promotive effect on both lipolysis and thermogenesis, and that these mechanisms underlie the anti-obesity effect of EA. The sympathetic nervous system (SNS) is known to play a role in thermogenesis. Additionally, obesity is characterized by a chronic low-grade inflammatory state. Based on these findings, the aim of the present study is to investigate the potential neuro-immune mechanisms underlying the therapeutic effect of EA in obesity. In the experiment, we used a high fat diet (HFD) rats model to study the effect of EA in reducing body weight. EA increases the activity of sympathetic nerves in inguinal white adipose tissue (iWAT), especially in the HFD group. Compared to HFD rats, EA can decrease sympathetic associated macrophage (SAM) and the level of norepinephrine transporter protein (Slc6a2). The relative uncoupling protein 1 expression shows EA increases thermogenesis in iWAT, and increases ß3 receptors. Interestingly, injecting ß antagonist in iWAT increases Slc6a2 protein levels. Additionally, the SNS-macrophage cross-talk response to EA showed in iWAT but not in epididymis white adipose tissue. The results of the present study indicate that EA exerts its anti-obesity effect via three mechanisms: (1) inhibition of SAMs and the norepinephrine transporter protein SlC6a2, (2) promoting SNS activity and thermogenesis, and (3) regulating immunologic balance.

[Effects of electroacupuncture on food intake and expression of lipid receptors of taste buds in the tongue and hippocampus in obese rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on food intake, body weight, number of taste bud cells and the expression of lipid taste bud receptor (CD36), Gα-gustducin, post-synaptic density protein 95 (PSD95) and neurofilament light chain (NFL) proteins in the tongue or hippocampus in obese rats, so as to explore its mechanism underlying reducing body weight. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups (n=10 in each group, 5 rats for H.E. staining and immunohistochemistry, and 5 for Western blot). The obesity model was established by feeding the rats with high fat diet for 11 weeks. Following successful modeling, EA (2 Hz/15 Hz, 1.0-1.2 mA) was applied to "Tianshu" (ST25) for 30 min, once a day, 5 times/week for 5 weeks. The body length, body weight and maximum daily food consumption were recorded every day, followed by calculating the lee's index. Histopathological changes of the circumvallate papillae (CVP) and number of taste bud cells and CD36 were detected by HE staining and immunohistochemistry (IHC), separately. The expression levels of CD36, PSD95 and NFL proteins in the hippocampus were detected by Western blot. RESULTS: The body weight, Lee's index and daily food consumption were significantly higher in the model group than in the control group (P<0.01), and were significantly lowered after EA intervention in comparison with the model group (P<0.01), suggesting an improvement of obesity. H.E. staining displayed that the CVP area and the number of taste bud cells were obviously decreased in the model group in contrast to the control group (P<0.01), and were notably increased in the EA group in contrast to the model group (P<0.05, P<0.01). IHC and Western blot showed that the expression levels of CD36 in the tongue and hippocampus were obviously up-regulated in the model group relevant to the control group (P<0.01, P<0.05), and considerably down-regulated in the EA group relevant to the model group (P<0.05, P<0.01). The expression levels of Gα-gustducin in the tongue, and PSD95 and NFL in the hippocampus were remarkably decreased in the model group relevant to the control group (P<0.01, P<0.05), and significantly increased in the EA group relevant to the model group (P<0.01, P<0.05). CONCLUSION: EA can reduce daily food consumption and body weight in obese rats, which is associated with its effects in down-regulating the expression of CD36 in taste buds and hippocampus, and up-regulating the expression of Gα-gustducin in the tongue, and PSD95 and NFL proteins in the hippocampus. It suggests that EA may regulate the feeding behavior of obese rats by influencing the cognitive memory mechanism involved in CD36 in hippocampus.

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis.

Background: Previous studies had suggested that electroacupuncture (EA) can promote white adipose tissue (WAT) browning to counter obesity. But the mechanism was still not very clear. Aim: In this study, we aim to study the effect of EA on promoting inguinal WAT (iWAT) browning and its possible mechanism. Method: Three-week-old rats were randomly divided into a normal diet (ND) group and a high-fat diet (HFD) group. After 10 weeks, the HFD rats were grouped into HFD + EA group and HFD control group. Rats in the EA group were electro-acupunctured for 4 weeks on Tianshu (ST25) acupoint under gas anesthesia with isoflurane, while the rats in HFD group were under gas anesthesia only. Body weight and cumulative food intake were monitored, and H&E staining was performed to assess adipocyte area. The effect of EA on WAT was assessed by qPCR, immunoblotting, immunoprecipitation and Co-immunoprecipitation. Mitochondria were isolated from IWAT to observe the expression of mitochondrial transcription factor A (TFAM). Results: The body weight, WAT/body weight ratio and cumulative food consumption obviously decreased (P < 0.05) in the EA group. The expressions of brown adipose tissue (BAT) markers were increased in the iWAT of EA rats. Nevertheless, the mRNA expressions of WAT genes were suppressed by 4-week EA treatment. Moreover, EA increased the protein expressions of SIRT-1, PPARγ, PGC-1α, UCP1 and PRDM16 which trigger the molecular conversion of iWAT browning. The decrease of PPARγ acetylation was also found in EA group, indicating EA could advance WAT-browning through SIRT-1 dependent PPARγ deacetylation pathway. Besides, we found that EA could activate AMPK to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. Conclusion: In conclusion, EA can remodel WAT to BAT through inducing SIRT-1 dependent PPARγ deacetylation, and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. This may be one of the mechanisms by which EA affects weight loss.

[Effect of electroacupuncture or moxibustion of "Tianshu" (ST25) on intragastric pressure in rats].

OBJECTIVE: To observe the effect of electroacupunctur (EA) and moxibustion of left or right "Tian-shu" (ST25) on intragastric pressure (IGP) in normal rats. METHODS: Twenty male SD rats were equally and randomly divided into EA group and moxibustion group. EA (2 Hz/15 Hz, 2 mA) or moxibustion (46-48 ℃) was applied to unilate-ral ST25 for 2 min. The IGP was detected by using a pressure-transducer and an amplifier before and after EA or moxibustion. RESULTS: Compared with pre-intervention, the IGP was significantly decreased after EA or moxibustion stimulation of both left and right ST25 (P<0.05). The IGP levels during 0-30 s and 30-60 s of EA stimulation of both left and right ST25 were significantly lower than those of moxibustion (P<0.05). The IGP-lowering effect of EA on the left ST25 was evidently stronger than that of the right ST25 (P<0.05), but without significant difference between the bilateral sides in moxibustion-induced IGP reduction (P>0.05). CONCLUSION: Both EA and moxibustion of ST25 can lower IGP, and the effect of EA is significantly stronger than that of moxibustion in normal rats. In addition, the IGP-lowering effect of EA of the left ST25 is markedly stronger than that of the right ST25, suggesting a lateral advantage effect.

EA at PC6 Promotes Gastric Motility: Role of Brainstem Vagovagal Neurocircuits.

BACKGROUND: We aimed to assess whether electroacupuncture (EA) at PC6 affects gastric motility via the vagovagal reflex and if so whether brainstem vagovagal neurocircuits and related transmitters are involved. METHODS: Gastric motility was measured in male Sprague-Dawley (SD) rats by placing a small manometric balloon in the gastric antrum. The rats were subjected to control, sham surgery, vagotomy, sympathectomy, and microinjection group, including artificial cerebrospinal fluid, gamma-aminobutyric acid (GABA), and glutamic acid (L-Glu). The effect of EA at PC6 on gastric motility was measured. Moreover, electrophysiological testing was used to measure the effect of EA at PC6 on the parasympathetic and sympathetic nerves. In addition, artificial cerebrospinal fluid, L-Glu, and GABA have been microinjected into the dorsal motor nucleus of the vagus (DMV) to measure the changes in gastric motility and parasympathetic nerve discharge induced by EA at PC6. KEY RESULTS: EA facilitated the gastric motility in control group. In the vagotomy group, gastric motility was not affected by EA at PC6. However, in the sympathectomy group, gastric motility was similar to control group. Acupuncture at PC6 increased parasympathetic nerve discharge but not sympathetic nerve discharge. Furthermore, the microinjection of L-Glu into the DMV increased gastric motility, although EA at PC6 showed no remarkable change in this group. The injection of GABA reduced gastric motility and parasympathetic nerve discharge, but EA at PC6 significantly increased gastric motility and the parasympathetic nerve discharge in this group. CONCLUSIONS AND INFERENCES: EA at PC6-primarily by inhibiting GABA transmission to DMV-reduced the inhibition of efferent vagal motor fibers and thus promoted efferent vagus nerve activity and increased gastric motility.

Electroacupuncture at ST36 modulates gastric motility via vagovagal and sympathetic reflexes in rats.

BACKGROUND: Electroacupuncture (EA) at ST36 can significantly improve gastrointestinal symptoms, especially in promoting gastrointestinal motility. The automatic nervous system plays a main role in EA, but few studies exist on how vagovagal and sympathetic reflexes affect EA to regulate gastrointestinal motility. AIM: To study the role of vagovagal and sympathetic reflexes in EA at ST36, as well as the associated receptor subtypes that are involved. METHODS: Gastric motility was measured with a manometric balloon placed in the gastric antrum area in anesthetized animals. The peripheral nervous discharge was measured using a platinum electrode hooking the vagus or greater splanchnic nerve, and the central nervous discharge was measured with a glass microelectrode in the dorsal motor nucleus of the vagus (DMV). The effects and mechanisms of EA at ST36 were explored in male Sprague-Dawley rats which were divided in to a control group, vagotomy group, sympathectomy group, and microinjection group [including an artificial cerebrospinal fluid group, glutamate (L-Glu) group, and γ-aminobutyric acid (GABA) group] and in genetically modified male mice [ß1ß2 receptor-knockout (ß1ß2-/-) mice, M2M3 receptor-knockout (M2M3-/-) mice, and wild-type control mice]. RESULTS: EA at ST36 promoted gastric motility during 30-120 s. During EA, both vagus and sympathetic nerve discharges increased, with a much higher frequency of vagus nerve discharge than sympathetic discharge. The gastric motility mediated by EA at ST36 was interdicted by vagotomy. However, gastric motility mediated by EA at ST36 was increased during 0-120 s by sympathectomy, which eliminated the delay effect of EA during 0-30 s, but it was lower than the control group during 30-120 s. Using gene knockout mice and their wild-type controls to explore the receptor mechanisms, we found that EA at ST36 decreased gastric motility in M2/3-/- mice, and promoted gastric motility in ß1/2-/- mice. Extracellular recordings showed that EA at ST36 increased spikes of the DMV. Microinjection of L-Glu into the DMV increased gastric motility, while EA at ST36 decreased gastric motility during 0-60 s, and promoted gastric motility during 60-120 s. Injection of GABA reduced or increased gastric motility, and reduced the promoting gastric motility effect of EA at ST36. CONCLUSION: These data suggest that EA at ST36 modulates gastric motility via vagovagal and sympathetic reflexes mediated through M2/3 and ß1/2 receptors, respectively. Sympathetic nerve activity mediated through ß1/2 receptors is associated with an early delay in modulation of gastric motility by EA at ST36.

[Influence of electroacupuncture of "Zhongwan" (CV12) and "Zusanli" (ST36) in different combinations of stimulating strength and sequence on intragastric pressure in normal rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zhongwan" (CV12) and "Zusanli" (ST36) in different combinations of stimulating parameters on intragastric pressure (IGP) in normal rats so as to explore their best combinations for promoting gastrointestinal mobility. METHODS: A total of 90 male SD rats were randomly divided into 6 EA groups：CV12-1 mA＋ST36-1 mA, CV12-1 mA＋ST36-2 mA, CV12-1 mA＋ST36-4 mA, ST36-1 mA＋CV12-1 mA, ST36-2 mA＋CV12-1 mA, and ST36-4 mA＋CV12-1 mA which the first acupoint was stimulated first, followed by the second in each group (n＝15 rats/group). Before (1 min), and 0-30 s, 30-60 s, 60 -90 s, and 90-120 s during EA stimulation of the left ST36 or CV12 first or later, the IGP was measured via an inserted intragastric balloon, a connected pressure transducer and an amplifier. Changes of the IGP were analyzed using 2×3×4 factorial design. RESULTS: 1) During 0-30 s, EA-CV12 showed an obvious inhibitory effect on IGP(P<0.05) while EA-ST36 showed a mild exciting effect (P>0.05). 2) Compared with the IGP level of 0-30 s, the IGP levels of 30-120 s were significantly decreased in all the groups (P<0.01). 3) In the CV12-1 mA/ST 36-1 mA groups, only the IGP level of 0-30 s was affected by the EA-stimulating order (P<0.05). In the CV12-1 mA/ST36-2 mA groups, both the IGP levels during 0-30 s and 90-120 s were obviously affected by EA-stimulating sequence. In the CV12-1 mA/ST36-4 mA groups, the IGP level during 0-120 s was affected by EA-stimulating order. 4) Only in the condition of EA-CV12 stimulating first and EA-ST36 second and at 4 mA, the reduction effect of IGP of EA-CV12 was antagonized. There are marked interaction effects between the EA strength and acupoint EA stimulating sequence, and between the time course and acupoint EA stimulating sequence (P<0.01), but no significant interaction effects were found between the time course and stimulating strength, and among the EA stimulating strength, time course and acupoint EA stimulating sequence (P>0.05). CONCLUSION: Simultaneous EA stimulation of ST36 and CV12 has an antagonistic effect on IGP in normal rats, which is affected by the stimulating sequence, stimulating strength and time course.

[Discussion on the cognition and development process of experimental animal acupoints].

To review the development history of the experimental animal acupoints. To analyze different historical periods, the names of animal acupoints, positioningmethods and references, it is believed that the understanding of experimental animal acupoints has gone through four stages, including initiation, accumulation, specification and standards. At the same time, some important events in the development of experimental animal acupoints were sorted out, including the publication of key papers, books, teaching materials, and the convening of important conferences. In addition, the significance of the above stages of development and the relationship between them were also analyzed to provide basic clues and evidence for the rational understanding of the characteristics and laws of experimental animals. It is concluded that the development of experimental animal acupoints has evolved from simple to complex, from fuzzy to precise.