American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Higher AMPK activation in mouse oxidative compared with glycolytic muscle does not correlate with LKB1 or CaMKKβ expression.","authors":"Romain Bernasconi, Kärol Soodla, Alex Sirp, Kairit Zovo, Maria Kuhtinskaja, Tiit Lukk, Marko Vendelin, Rikke Birkedal","doi":"10.1152/ajpendo.00261.2024","DOIUrl":"10.1152/ajpendo.00261.2024","url":null,"abstract":"<p><p>AMP-activated protein kinase (AMPK) is an energy-sensing serine/threonine kinase involved in metabolic regulation. It is phosphorylated by the upstream liver kinase B1 (LKB1) or calcium/calmodulin-dependent kinase kinase 2 (CaMKKβ). In cultured cells, AMPK activation correlates with LKB1 activity. The phosphorylation activates AMPK, shifting metabolism toward catabolism and promoting mitogenesis. In muscles, inactivity reduces AMPK activation, shifting the phenotype of oxidative muscles toward a more glycolytic profile. Here, we compared the basal level of AMPK activation in glycolytic and oxidative muscles and analyzed whether this relates to LKB1 or CaMKKβ. Using Western blotting, we assessed AMPK expression and phosphorylation in soleus, gastrocnemius (GAST), extensor digitorum longus (EDL), and heart from C57BL6J mice. We also assessed LKB1 and CaMKKβ expression, and CaMKKβ activity in tissue homogenates. AMPK activation was higher in oxidative (soleus and heart) than in glycolytic muscles (gastrocnemius and EDL). This correlated with AMPK α1-isoform expression, but not LKB1 and CaMKKβ. LKB1 expression was sex dependent and lower in male than female muscles. CaMKKβ expression was very low in skeletal muscles and did not phosphorylate AMPK in muscle lysates. The higher AMPK activation in oxidative muscles is in line with the fact that activated AMPK maintains an oxidative phenotype. However, this could not be explained by LKB1 and CaMKKβ. These results suggest that the regulation of AMPK activation is more complex in muscle than in cultured cells. As AMPK has been proposed as a therapeutic target for several diseases, future research should consider AMPK isoform expression and localization, and energetic compartmentalization.<b>NEW & NOTEWORTHY</b> It is important to understand how AMP-activated kinase, AMPK, is regulated, as it is a potential therapeutic target for several diseases. AMPK is activated by liver kinase B1, LKB1, and calcium/calmodulin-dependent kinase kinase 2, CaMKKβ. In cultured cells, AMPK activation correlates with LKB1 expression. In contrast, we show that AMPK-activation was higher in oxidative than glycolytic muscle, without correlating with LKB1 or CaMKKβ expression. Thus, AMPK regulation is more complex in highly compartmentalized muscle cells.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E21-E33"},"PeriodicalIF":4.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic NPY boosts thermogenic adipocytes.","authors":"Luis Leon-Mercado, Laurent Gautron","doi":"10.1152/ajpendo.00377.2024","DOIUrl":"10.1152/ajpendo.00377.2024","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E44-E45"},"PeriodicalIF":4.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early exposure to a cholinergic receptor blocking agent mitigates adult obesity and protects pancreatic islet function in male rats.","authors":"Ananda Malta, Camila Cristina Ianoni Matiusso, Lucas da Silva de Lima, Tatiane Aparecida Ribeiro, Laize Peron Tófolo, Douglas Lopes Almeida, Veridiana Mota Moreira, Isabela Peixoto Martins, Audrei Pavanello, Paulo Cezar de Freitas Mathias","doi":"10.1152/ajpendo.00191.2024","DOIUrl":"10.1152/ajpendo.00191.2024","url":null,"abstract":"<p><p>We tested the hypothesis that attenuation of the circulating insulin level in rats during early life can provide sustained protection against diet-induced obesity and metabolic dysfunction in adulthood. Male Wistar rats received intraperitoneal scopolamine butylbromide (SB) during the first 12 days of suckling, whereas control rats received 0.9% saline injections. The animals were weaned on <i>day 21</i> and fed a normal chow diet. At 60 days of age, the control and SB groups were fed a normal chow diet (ND; 4.5% fat) or a high-fat diet (HF; 35% fat) until 90 days of age to induce obesity and metabolic dysfunction. Insulin secretion, food intake, and body weight were measured. Pancreatic islet function, autonomic nervous system function, and glucose homeostasis were evaluated at 90 days of age. During lactation, the plasma insulin concentration was significantly lower in the SB groups than in the control group. SB rats also exhibited reduced body weight. The HF diet resulted in obesity, glucose intolerance, insulin resistance, disruption of insulin secretion, and vagal hyperactivity in adult control rats. Remarkably, SB-treated rats fed the HF diet showed attenuated body weight and adiposity and did not develop diet-induced glucose/insulin imbalance. In addition, vagal activity and adequate pancreatic islet insulin secretion were preserved. Offspring exposed to SB during early life are provided with long-lasting protection against obesity and metabolic complications induced by an HF diet. An attenuated circulating insulin level in early life may have far-reaching consequences on metabolic programming.<b>NEW & NOTEWORTHY</b> High insulin levels during early life may lead to the late development of obesity and diabetes. We investigated whether attenuation of insulin levels by using an antimuscarinic agent could prevent diet-induced obesity and diabetes. Rats' early exposure to an antimuscarinic agent reduced insulin levels during the lactation period and promoted protection against obesity and metabolic dysfunctions. Independent of the programming mechanisms, insulin levels during early life may be a defining factor of health or diseases later in life.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E34-E43"},"PeriodicalIF":4.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species differences of fatty liver diseases: comparisons between human and feline.","authors":"Like Ling, Ruilin Li, Mengqiong Xu, Junjie Zhou, Manli Hu, Xin Zhang, Xiao-Jing Zhang","doi":"10.1152/ajpendo.00014.2024","DOIUrl":"10.1152/ajpendo.00014.2024","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) has emerged as the most widespread chronic liver disease that poses significant threats to public health due to changes in dietary habits and lifestyle patterns. The transition from simple steatosis to nonalcoholic steatohepatitis (NASH) markedly increases the risk of developing cirrhosis, hepatocellular carcinoma, and liver failure in patients. However, there is only one Food and Drug Administration-approved therapeutic drug in the world, and the clinical demand is huge. There is significant clinical heterogeneity among patients with NAFLD, and it is challenging to fully understand human NAFLD using only a single animal model. Interestingly, felines, like humans, are particularly prone to spontaneous fatty liver disease. This review summarized and compared the etiology, clinical features, pathological characteristics, and molecular pathogenesis between human fatty liver and feline hepatic lipidosis (FHL). We analyzed the key similarities and differences between those two species, aiming to provide theoretical foundations for developing effective strategies for the treatment of NAFLD in clinics.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E46-E61"},"PeriodicalIF":4.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating interleukin-33 levels in obesity and type 2 diabetes: a systematic review and meta-analysis.","authors":"Ghalia Missous, Nicholas Van Panhuys","doi":"10.1152/ajpendo.00157.2024","DOIUrl":"10.1152/ajpendo.00157.2024","url":null,"abstract":"<p><p>Obesity and type 2 diabetes (T2D) are increasingly prevalent worldwide, and there is a critical need for novel interventions. Interleukin-33 (IL-33), an anti-inflammatory cytokine that regulates metabolism, is a promising biomarker for these conditions. The goal of this systematic review and meta-analysis is to examine the role of IL-33 in obesity and T2D, assessing its potential in predicting disease progression. A systematic search was performed on Scopus, Web of Science, and PubMed up until May 30, 2023. Each study was assessed for quality and sources of bias using the relevant critical appraisal checklists. Meta-analyses were conducted to compare IL-33 levels in individuals with obesity and T2D versus healthy controls (HC), and in obesity alone versus HC. Eighteen studies were included in the systematic review, and nine qualified for meta-analyses. The analyses showed insufficient evidence to suggest a significant difference in IL-33 levels between individuals with T2D and HC (mean difference, MD = -79.95, 95% CI [-241.38; 81.48]), with substantial heterogeneity across the studies observed (<i>I</i>² = 97.1%, τ² = 33,549.15). Similarly, there was insufficient evidence to suggest a significant difference between nondiabetic individuals with obesity and HC (MD = -7.31, 95% CI [-25.74; 11.13]), and heterogeneity was noted (<i>I</i>² = 86.2%, τ² = 342.45). There is insufficient evidence to indicate significant differences in IL-33 levels in individuals with T2D or obesity compared with HC. The results suggest a need for improved IL-33 measurement methods to reduce heterogeneity, enhancing understanding of the role of IL-33 in obesity and T2D, and informing future research and therapeutic strategies.<b>NEW & NOTEWORTHY</b> Our research finds an inconclusive relationship between IL-33 serum levels in individuals with type 2 diabetes (T2D) and nondiabetic individuals with obesity. In addition, we note a potential gender association with IL-33 serum levels. Further studies with larger cohorts are required to assess the significance of serum IL-33 in T2D and obesity. Urgent standardization is needed in IL-33 quantification and reporting methods for reliable comparisons.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E686-E699"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic shifts in ratio of ucOcn to cOcn toward bone resorption contribute to age-dependent bone loss in male mice.","authors":"Matthew Bernhard, Obinna Okorie, Wei-Ju Tseng, Mengcun Chen, Julia Danon, Mingshu Cui, Elisabeth Lashbrooks, Yanmei Yang, Bin Wang","doi":"10.1152/ajpendo.00294.2024","DOIUrl":"10.1152/ajpendo.00294.2024","url":null,"abstract":"<p><p>The study of the senile osteoporosis in men still lags significantly behind that in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 mo to delineate the mechanisms of aging effects on bone loss. We used the microcomputed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with the ratios of ucOcn-to-cOcn in mice from different age groups. The results showed that mouse trabecular bone mass reduced gradually with age, whereas cortical bone loss and mechanical property changes mostly occurred in advanced age. Our findings further demonstrated that the increase in osteoclast activity and the decrease in osteoblast function were significantly corelated with blood levels of ucOcn and cOcn, respectively. The dynamic metabolic changes of ucOcn to cOcn ratio were correlated with age-dependent bone loss in mice. In summary, metabolic shifts in the ratio of ucOcn to cOcn toward bone resorption from young adult to elderly mice contribute to the pathogenesis of age-related bone loss. Simultaneously monitoring blood ratios of ucOcn-to-cOcn may be useful to predict the status of bone mass in vivo.<b>NEW & NOTEWORTHY</b> To our knowledge, our finding in this study shows for the first time that metabolic shifts in ratio of ucOcn to cOcn toward bone resorption are markedly correlated with age-dependent bone loss in male mice. These findings for the effects of aging on bone loss will assist in studying the pathogenesis of human type II osteoporosis.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E711-E722"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of the gut microbiota, metabolites, and epigenetics in the effects of maternal exercise on offspring metabolism.","authors":"Jing Ren, Liyuan Zhou, Shunhua Li, Qian Zhang, Xinhua Xiao","doi":"10.1152/ajpendo.00200.2024","DOIUrl":"10.1152/ajpendo.00200.2024","url":null,"abstract":"<p><p>Metabolic diseases, including obesity, dyslipidemia, and type 2 diabetes, have become severe challenges worldwide. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that an adverse intrauterine environment can increase the risk of metabolic disorders in offspring. Studies have demonstrated that maternal exercise is an effective intervention for improving the offspring metabolic health. However, the pathways through which exercise works are unclear. It has been reported that the gut microbiota mediates the effect of maternal exercise on offspring metabolism, and epigenetic modifications have also been proposed to be important molecular mechanisms. Microbial metabolites can influence epigenetics by providing substrates for DNA or histone modifications, binding to G-protein-coupled receptors to affect downstream pathways, or regulating the activity of epigenetic modifying enzymes. This review aims to summarize the intergenerational effect of maternal exercise and proposes that gut microbiota-metabolites-epigenetic regulation is an important mechanism by which maternal exercise improves offspring metabolism, which may yield novel targets for the early prevention and intervention of metabolic diseases.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E760-E772"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal surge of adipose-secreted leptin is a robust predictor of fat mass trajectory in mice.","authors":"Olga Horakova, Petra Janovska, Ilaria Irodenko, Jana Buresova, Inge van der Stelt, Sara Stanic, Eliska Haasova, Nivasini Shekhar, Tatyana Kobets, Jaap Keijer, Petr Zouhar, Martin Rossmeisl, Jan Kopecky, Kristina Bardova","doi":"10.1152/ajpendo.00237.2024","DOIUrl":"10.1152/ajpendo.00237.2024","url":null,"abstract":"<p><p>The transient postnatal increase in circulating leptin levels, known as leptin surge, may increase later susceptibility to diet-induced obesity in rodents. However, the source of leptin during the surge needs to be better characterized, and the long-term effects of leptin are contradictory. Characterization of the interaction of leptin with the genetic background, sex, and other factors is required. Here, we focused on the impact of circulating leptin levels and several related variables, measured in 2- and 4-wk-old <i>i</i>) obesity-prone C57BL/6 (B6) and <i>ii</i>) obesity-resistant A/J mice. In total, 264 mice of both sexes were used. Posttranscriptionally controlled leptin secretion from subcutaneous white adipose tissue, the largest adipose tissue depot in mice pups, was the primary determinant of plasma leptin levels. When the animals were randomly assigned standard chow or high-fat diet (HFD) between 12 and 24 wk of age, the obesogenic effect of HFD feeding was observed in B6 but not A/J mice. Only leptin levels at 2 wk, i.e., close to the maximum in the postnatal leptin surge, correlated with both body weight (BW) trajectory throughout the life and adiposity of the 24-wk-old mice. Leptin surge explained 13 and 7% of the variance in BW and adiposity of B6 mice, and 9 and 35% of the variance in these parameters in A/J mice, with a minor role of sex. Our results prove the positive correlation between the leptin surge and adiposity in adulthood, reflecting the fundamental biological role of leptin. This role could be compromised in subjects with obesity.<b>NEW & NOTEWORTHY</b> The postnatal surge in circulating leptin levels in mice reflects particularly posttranscriptionally controlled release of this hormone from subcutaneous white adipose tissue. Leptinemia in 2-wk-old pups predicts both body weight and adiposity in adult mice fed a high-fat diet. The extent of these effects depends on genetically determined differences in propensity to obesity between C57BL/6 and A/J mice. The leptin effect on adiposity is compromised in the obesity-prone C57BL/6 mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E729-E745"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial β1-integrins are necessary for microvascular function and glucose uptake.","authors":"Nathan C Winn, Deborah A Roby, P Mason McClatchey, Ian M Williams, Deanna P Bracy, Michelle N Bedenbaugh, Louise Lantier, Erin J Plosa, Ambra Pozzi, Roy Zent, David H Wasserman","doi":"10.1152/ajpendo.00322.2024","DOIUrl":"10.1152/ajpendo.00322.2024","url":null,"abstract":"<p><p>Microvascular insulin delivery to myocytes is rate limiting for the onset of insulin-stimulated muscle glucose uptake. The structural integrity of capillaries of the microvasculature is regulated, in part, by a family of transmembrane adhesion receptors known as integrins, which are composed of an α and a β subunit. The integrin β1 (itgβ1) subunit is highly expressed in endothelial cells (ECs). EC itgβ1 is necessary for the formation of capillary networks during embryonic development, and its knockdown in adult mice blunts the reactive hyperemia that manifests during ischemia reperfusion. In this study, we investigated the contribution of EC itgβ1 in microcirculatory function and glucose uptake, with an emphasis on skeletal muscle. We hypothesized that loss of EC itgβ1 would impair microvascular hemodynamics and glucose uptake during insulin stimulation, creating \"delivery\"-mediated insulin resistance. An itgβ1 knockdown mouse model was developed to avoid the lethality of embryonic gene knockout and the deteriorating health resulting from early postnatal inducible gene deletion. We found that mice with (<i>itgβ1</i>^fl/flSCLcre) and without (<i>itgβ1</i>^fl/fl) inducible stem cell leukemia cre recombinase (SLCcre) expression at 10 days post cre induction have comparable exercise tolerance and pulmonary and cardiac functions. We quantified microcirculatory hemodynamics using intravital microscopy and the ability of mice to respond to the high metabolic demands of insulin-stimulated muscle using a hyperinsulinemic-euglycemia clamp. We show that <i>itgβ1</i>^fl/flSCLcre mice compared with <i>itgβ1</i>^fl/fl littermates have <i>1</i>) deficits in capillary flow rate, flow heterogeneity, and capillary density; <i>2</i>) impaired insulin-stimulated glucose uptake despite sufficient transcapillary insulin efflux; and <i>3</i>) reduced insulin-stimulated glucose uptake due to perfusion-limited glucose delivery. Thus, EC itgβ1 is necessary for microcirculatory function and to meet the metabolic challenge of insulin stimulation.<b>NEW & NOTEWORTHY</b> The microvasculature is an important site of resistance to muscle glucose uptake. We show that microvasculature integrins determine the exchange of glucose between the circulation and muscle. Specifically, a 30% reduction in the expression of endothelial integrin β1 subunit is sufficient to cause microcirculatory dysfunction and lead to insulin resistance. This emphasizes the importance of endothelial integrins in microcirculatory function and the importance of microcirculatory function for the ability of muscle to consume glucose.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E746-E759"},"PeriodicalIF":4.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine vasopressin induces analgesic effects and inhibits pyramidal cells in the anterior cingulate cortex in spared nerve injured mice.","authors":"Hua-Xing Si, Xiao-Die Liu, Chao-Yi Sun, Shan-Ming Yang, Han Zhao, Xian-Xia Yan, Tao Chen, Pan Wang","doi":"10.1152/ajpendo.00361.2024","DOIUrl":"10.1152/ajpendo.00361.2024","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a severe disease caused by a primary disease or lesion affecting the somatosensory nervous system. It is reported that NP is related to the increased activity of glutamatergic pyramidal cells and changed neural oscillations in the anterior cingulate cortex (ACC). Arginine vasopressin (AVP), a neurohypophyseal hormone, has been shown to cause pain-alleviating effects when applied to the peripheral system. However, the extent to which, and the mechanisms by which, AVP induces analgesic effects in the central nervous system remains unclear. In the present study, we observed that intranasal delivery of AVP inhibited mechanical pain, thermal pain, and spontaneous pain sensitivity in mice with spared nerve injury. Meanwhile, AVP application exclusively reduced the FOS expression in the pyramidal cells but not interneurons in the ACC. In vivo electrophysiological recording of the ACC further showed that AVP application not only inhibited the theta oscillation in local field potential analysis but also reduced the firing rate of spikes of pyramidal cells in the ACC in neuropathic pain mice. In summary, AVP induces analgesic effects by inhibiting neural theta oscillations and the spiking of pyramidal cells of the ACC in mice with neuropathic pain, which should provide new potential noninvasive methods for clinical treatment of chronic pain.<b>NEW & NOTEWORTHY</b> Following intranasal administration of arginine vasopressin (AVP), the pain thresholds for mechanical and thermal nociception significantly increased in the spared nerve injury (SNI) group; exogenous intranasal delivery of AVP improved the physical coordination of SNI mice, resulting in an analgesic effect; AVP treatment significantly reduced the increased firing rate of PYR^ACC of the SNI group; AVP treatment significantly inhibited the elevated theta oscillation in the anterior cingulate cortex (ACC) in SNI mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E700-E710"},"PeriodicalIF":5.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}