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.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

AIM: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. MATERIALS AND METHODS: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. RESULTS: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. CONCLUSION: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling 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.

Acupoints catgut embedding recovers leptin resistance via improving autophagy progress mediated by AMPK-mTOR signaling in obese mice.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

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.

Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection.

BACKGROUND: Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. PURPOSE: This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. METHODS: BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. RESULTS: Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. CONCLUSION: Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.