American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Promotion of obesity by fibroblast growth factor 21-oxytocin system dysfunction due to sugar-specific hyperphagia.","authors":"Hajime Mori, Kanako Inoue, Sho Matsui, Yasuo Oguri, Satoshi Tsuzuki, Tsutomu Sasaki","doi":"10.1152/ajpendo.00138.2025","DOIUrl":"10.1152/ajpendo.00138.2025","url":null,"abstract":"<p><p>Fibroblast growth factor (FGF) 21 activates oxytocin (OXT) neurons in the hypothalamus and suppresses simple sugar preference; however, alterations in the FGF21-OXT system in obesity remain unclear. In this study, we examined alterations in FGF21 secretion to systemic circulation and FGF21 sensitivity of OXT neurons in obesity, and the effects of FGF21-OXT dysfunction on feeding and body weight regulation. High-fat high-sucrose diet (HFHSD) feeding promoted hypersecretion of FGF21. The administration of recombinant FGF21 to normal diet-fed mice significantly activated OXT neurons in the paraventricular nucleus of the hypothalamus; this response was attenuated in HFHSD-fed mice. OXT neuron-specific FGF21 receptor-deficient (OXT<i>-Klb</i> cKO) mice were used as a model of FGF21-OXT dysfunction. The preference and appetite for sugar and fat were assessed using two-food choice test, two-bottle choice test, and lick microstructure analyses. The cKO mice showed an increased preference and appetite for FGF21-inducing simple sugars but not fat. These mice gained more weight when fed an HFHSD, which caused hyperphagia, but not when fed a high-fat diet. Therefore, obesity causes FGF21-OXT dysfunction, which promotes diet-induced obesity by increasing sugar appetite, suggesting that the dysfunction of the FGF21-OXT system plays a role in the vicious cycle of sugar-based diet-induced obesity in mice.<b>NEW & NOTEWORTHY</b> FGF21 activates OXT neurons and suppresses simple sugar preference, but the relationship between FGF21-OXT system and obesity is unknown. Here, we showed that obesity causes FGF21-OXT dysfunction and promotes sugar appetite and diet-induced obesity, suggesting that there is a vicious cycle of FGF21-OXT dysfunction and obesity in mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E18-E24"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186296","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":"Regulation of perinatal estrogen levels on primordial follicle formation and activation in mouse.","authors":"Rui Xu, Lu Yin, Yiqian Zhang, Yinxiang Niu, Sihai Lu, Yaju Tang, Sha Peng, Menghao Pan, Baohua Ma","doi":"10.1152/ajpendo.00026.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00026.2025","url":null,"abstract":"<p><p>Primordial follicle formation and activation are key for the reproductive ability of females. In mice, primordial follicles are formed and begin to activate during the perinatal period, when the levels of estrogen are fluctuating. Whether estrogen plays a role in primordial follicle formation and activation, and its mechanism are still not fully elucidated. In this study, estrogen remained at high levels before birth and declined after birth. When fetal mouse ovaries (E16.5) were cultured in vitro, higher levels (10 nM) of estrogen maintained the germ cell cysts, prevented primordial follicles from forming prematurely, and promoted the full differentiation of oocytes. Furthermore, it was found that estrogen-regulated JNK-signal pathway through both nuclear and membrane receptors, thereby inhibited the degradation of E-cadherin and maintained the germ cell cysts. After birth, ovarian estrogen concentration decreases and is accompanied by the activation of primordial follicles. Hence, the ovaries of newborn mice (P3) were treated with lower concentrations (0.1 nM) of estrogen to investigate the effect of estrogen on primordial follicle activation. The results demonstrated that estrogen regulated the protein expression of cAMP synthase adenylyl cyclase 3 (ADCY3) through the membrane receptor G-protein-coupled estrogen receptor (GPER), increased the level of cAMP in the ovary, and activated the cAMP-PKA signaling pathway to promote the activation of primordial follicles. This study revealed the regulatory role of perinatal estrogen levels on primordial follicle formation and activation before and after birth, which would help to better understand the potential physiological effect of estrogen in vivo.<b>NEW & NOTEWORTHY</b> In this study, the roles and underlying mechanisms of perinatal estrogen level changes in primordial follicle formation and activation in mice were elucidated. The elevated estrogen levels before birth inhibited the premature formation of primordial follicles and enhanced the quality of oocyte differentiation. Conversely, the reduced estrogen levels following birth promoted the activation of primordial follicles.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 6","pages":"E772-E786"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956570","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":"Catabolic to anabolic transition during nutritional rehabilitation of female adolescents with anorexia nervosa.","authors":"Yael Levy-Shraga, Idit Ron, Adi Enoch-Levy, Rina Hemi, Hannah Kanety, Ido Wolf, Daniel Stein, Amir Tirosh, Tami Rubinek, Dalit Modan-Moses","doi":"10.1152/ajpendo.00523.2024","DOIUrl":"10.1152/ajpendo.00523.2024","url":null,"abstract":"<p><p>Anorexia nervosa (AN) is associated with profound changes in glucose homeostasis, activity of the GH-IGF-1 axis, and adipose tissue, bone, and protein metabolism. We aimed to characterize the transition from a catabolic to anabolic state during the nutritional rehabilitation of female adolescent inpatients with AN. The study comprised 41 patients (aged 15.6 ± 1.6 yr). Blood samples were obtained at the time of admission and upon attainment of target weight. A subgroup of 18 patients also had blood samples obtained during the early refeeding period. Changes in body mass index (BMI) and BMI-SDS during hospitalization (5.1 ± 2.0 mo) were positively correlated with changes in markers of anabolism including IGF-1 (<i>r</i> = 0.424, <i>P</i> = 0.006), procollagen type I N-terminal propeptide (P1NP) (<i>r</i> = 0.375, <i>P</i> = 0.016), klotho (<i>r</i> = 0.468, <i>P</i> = 0.002), and alkaline phosphatase (ALP) (<i>r</i> = 0.051, <i>P</i> = 0.001) and were negatively correlated with the change in cortisol levels (<i>r</i> = -0.331, <i>P</i> = 0.035). Furthermore, changes in markers of anabolism were intercorrelated. IGF-1 increased consistently throughout the study period (<i>P</i> < 0.001); however, other variables showed a biphasic pattern. During the early refeeding period, there was a decrease in C-terminal telopeptides of type I collagen (CTX-1) (<i>P</i> < 0.001), uric acid (<i>P</i> < 0.001), cortisol (<i>P</i> = 0.056), fatty acid-binding protein 4 (FABP4) (<i>P</i> = 0.04), and klotho (<i>P</i> = 0.038) levels, whereas urea/creatinine ratio (UCR) (<i>P</i> = 0.045) increased. During the later phase, there was an increase in ALP (<i>P</i> = 0.039), insulin (<i>P</i> = 0.04), homeostatic model assessment for insulin resistance (HOMA-IR) (<i>P</i> = 0.06), and klotho levels (<i>P</i> = 0.02). In conclusion, the early refeeding period was characterized by a decrease in markers of catabolism, whereas the later phase was characterized by an increase in anabolic markers. We suggest that IGF-1, UCR, and klotho may be used as markers of reversal of catabolism and shift toward anabolism in patients with severe malnutrition.<b>NEW & NOTEWORTHY</b> We provide a comprehensive temporal characterization of changes in biochemical markers of glucose homeostasis, GH-IGF-1 axis activity, and adipose tissue, bone, and protein metabolism during refeeding of adolescents with anorexia nervosa. Although IGF-I levels increased continuously, other markers showed a biphasic pattern: an early decrease in catabolic markers, followed by an increase in anabolic markers later during hospitalization. IGF-1, urea/creatinine ratio, and klotho emerged as potential clinical biomarkers of catabolic to anabolic transition in patients with severe malnutrition.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E845-E855"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966207","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":"Urinary exosomes exacerbate diabetic kidney disease by promoting NLRP3 inflammasome activation via the microRNA-516b-5p/SIRT3/AMPK pathway.","authors":"Haiying Zhang, Yubo Jiang, Jun Song, Shaoqing Wang, Jianhong Lu, Fuxin Wei, Xiu Li","doi":"10.1152/ajpendo.00527.2024","DOIUrl":"10.1152/ajpendo.00527.2024","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus. Urinary exosomal miRNAs play a prominent regulatory role in the pathogenesis of DKD, but the potential mechanisms remain largely unknown. Our research was designed to explain the pathogenesis of urine-derived exosomal microRNA-516b-5p (miR-516b-5p) in the DKD development. Urine-derived exosomes were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Immunofluorescence staining was used to detect cellular internalization. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis was performed to measure the levels of miR-516b-5p and SIRT3. The secretion of inflammatory cytokines and Caspase-1 activity were evaluated via ELISA and flow cytometry, respectively. Expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome markers and genes associated with the SIRT3/AMPK signaling pathway were measured using Western blot. Bioinformatics tools and dual-luciferase reporter gene assay were used to confirm the correlation between miR-516b-5p and SIRT3. Blood glucose and renal function indexes were determined by the corresponding commercial kits. Hematoxylin and eosin (H&E) staining was exploited to examine the renal pathological changes. MiR-516b-5p was memorably upregulated in HKB-20 cells exposed to DKD-Exo. DKD-Exo introduction led to an increase in Caspase-1 activity, promoted inflammatory response and NLRP3 inflammasome activity, and inactivation of SIRT3/AMPK signaling pathway, which was partially reversed by silencing miR-516b-5p. SIRT3 was identified as a target gene of miR-516b-5p. SIRT3 overexpression reversed the influences of DKD-Exo and miR-516b-5p mimic. In the in vivo model, DKD-Exo exacerbated streptozotocin (STZ)-induced kidney injury through promoting inflammatory response and activating the NLRP3 inflammasome. Urinary exosomal miR-516b-5p plays a key role in DKD by promoting inflammatory response and activating the NLRP3 inflammasome through the SIRT3/AMPK pathway.<b>NEW & NOTEWORTHY</b> Urinary exosomal miR-516b-5p plays a key role in diabetic kidney disease (DKD) by promoting inflammatory response and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation through the SIRT3/AMPK pathway.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E911-E923"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959922","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":"Impact of preoperative NAFLD status on restoration of pancreatic β-cell function after laparoscopic sleeve gastrectomy.","authors":"Yuki Oe, Akinobu Nakamura, Kyu Yong Cho, Takahiro Takase, Koji Ogawa, Yuma Ebihara, Masato Yoshikawa, Aika Miya, Hiroshi Nomoto, Hiraku Kameda, Goki Suda, Kohsuke Kudo, Naoya Sakamoto, Satoshi Hirano, Tatsuya Atsumi","doi":"10.1152/ajpendo.00484.2024","DOIUrl":"10.1152/ajpendo.00484.2024","url":null,"abstract":"<p><p>Although pancreatic beta-cell insufficiency is ameliorated after bariatric and metabolic surgery in subjects with obesity and type 2 diabetes (T2D), the mechanism and preoperative factors related to this amelioration have been uncertain. This study investigated the effect of laparoscopic sleeve gastrectomy (LSG) on beta-cell function. The preoperative characteristics and factors associated with the degree of postoperative changes in beta-cell function in those subjects were explored as well. In this subanalysis of our prospective observational study, subjects with obesity and T2D underwent oral glucose tolerance tests (OGTTs) and magnetic resonance imaging (MRI), at the baseline and the end of the 1-year follow-up period. Beta-cell function was evaluated by the insulin secretion-sensitivity index-2 (ISSI-2) and disposition index (DI), and the preoperative factors associated with these changes were examined. In 18 eligible subjects, glucose tolerance improved, ISSI-2 increased significantly, and DI also tended to increase 1 year after LSG. The change in ISSI-2 correlated with preoperative liver fibrosis assessed by MR elastography (<i>r</i> = -0.49, <i>P</i> < 0.05). In 16 subjects without severe fibrosis, changes in DI correlated with preoperative MRI-estimated proton density fat fraction (<i>r</i> = -0.52, <i>P</i> < 0.05). Neither as glycemic control nor visceral fat was significantly associated with the degree of amelioration in beta-cell function. Pancreatic beta-cell function improved at 1-year postoperative to LSG in subjects with obesity and T2D. Preoperative liver fibrosis and steatosis were associated with a lower degree of postoperative pancreatic beta-cell improvement.<b>NEW & NOTEWORTHY</b> In the present study, pancreatic beta-cell function improved at 1 year postoperatively in subjects with obesity and type 2 diabetes (T2D) who underwent laparoscopic sleeve gastrectomy. Preoperative liver fibrosis and steatosis were associated with a lower degree of postoperative pancreatic beta-cell improvement. Considering that amelioration of pancreatic beta-cell function leads to better outcome of T2D, the finding of this association would be clinically significant.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E1013-E1020"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075440","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":"FOXM1 cooperates with ERα to regulate functional β-cell mass.","authors":"Guihong Peng, Elham Mosleh, Andrew Yuhas, Kay Katada, Devi Kasinathan, Christopher Cherry, Maria L Golson","doi":"10.1152/ajpendo.00438.2024","DOIUrl":"10.1152/ajpendo.00438.2024","url":null,"abstract":"<p><p>The transcription factor forkhead box (FOX)M1 regulates β-cell proliferation and insulin secretion. Our previous work demonstrates that expressing a constitutively active form of FOXM1 (FOXM1*) in β-cells increases β-cell function, proliferation, and mass in male mice. However, in contrast to what is observed in males, we demonstrate here that in female mice expression of FOXM1* in β-cells does not affect β-cell proliferation or glucose tolerance. Similarly, FOXM1* transduction of male but not female human islets enhances insulin secretion in response to elevated glucose. We therefore examined the mechanism behind this sexual dimorphism. Estrogen contributes to diabetes susceptibility differences between males and females, and estrogen receptor (ER)α is the primary mediator of β-cell estrogen signaling. Moreover, in breast cancer cells, ERα and FOXM1 work together to drive gene expression. We therefore examined whether FOXM1 and ERα functionally interact in β-cells. FOXM1* rescued elevated fasting glucose, glucose intolerance, and homeostatic model assessment of β-cell function (HOMA-B) in female mice with a β-cell-specific ERα deletion. Furthermore, in the presence of estrogen, the FOXM1 and ERα cistromes exhibit significant overlap in βTC6 β-cells. In addition, FOXM1 and ERα binding sites frequently occur in complex enhancers co-occupied by other islet transcription factors. These data indicate that FOXM1 and nuclear ERα cooperate to regulate β-cell function and suggest a general mechanism contributing to the lower incidence of diabetes observed in women.<b>NEW & NOTEWORTHY</b> Here we investigate why the effects of increasing FOXM1 activity in β-cells observed in male mice are not seen in female mice. ERα likely collaborates with FOXM1 and other transcription factors to enhance gene expression related to β-cell function. Higher estrogen levels in females may contribute to their increased insulin secretion and the more severe consequences of losing transcription factors like FOXM1 in males. Overall, these findings shed light on sex differences in diabetes susceptibility.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"328 6","pages":"E804-E821"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953477","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":"Muscle wasting and the response to exercise in lung-injured mice is not primarily driven through the glucocorticoid axis.","authors":"Chia-Chi Chuang Key, Lanazha Belfield, Jennifer Thi Wing Krall, Kevin W Gibbs, Chun Liu, Lina Purcell, Renee D Stapleton, Matthew E Poynter, Michael J Toth, Matthew Quinn, Swapan K Das, D Clark Files","doi":"10.1152/ajpendo.00039.2025","DOIUrl":"10.1152/ajpendo.00039.2025","url":null,"abstract":"<p><p>Muscle wasting is common in patients with acute respiratory distress syndrome (ARDS). We have previously shown that acute lung-injured (ALI) mice develop muscle atrophy driven by muscle E3 ubiquitin ligase muscle RING-finger protein 1 (MuRF1). The muscle atrophy response in ALI mice can be partially alleviated by short durations of moderate-intensity treadmill exercise through unclear mechanisms. Glucocorticoid receptor (GR) signaling has been implicated in muscle wasting and repair, and the MuRF1 promoter contains a glucocorticoid response element. We examined the contribution of muscle GR signaling in ALI-associated muscle wasting and the response to exercise. Intratracheal lipopolysaccharides were instilled into wild-type (WT) mice. Mice exercised for prescribed intensity and duration on a treadmill. GR knockdown was achieved through pharmacological inhibition and the use of muscle-specific GR knockout mice. Muscle structure and function was evaluated using physiological and histochemical techniques, and GR activation was assessed under multiple conditions. Muscle wasting in ALI mice was associated with a GR transcriptional response, which was suppressed by exercise. However, neither pharmacological inhibition of muscle GR signaling, nor genetic deletion of muscle GR prevented skeletal muscle wasting or recapitulated the benefits of exercise in WT ALI mice. Moreover, RNAseq of tibialis anterior and diaphragm skeletal muscle in WT mice revealed that exercise influenced genes related to skeletal muscle tissue remodeling, but pathway analysis suggested that this was unrelated to the glucocorticoid axis. GR signaling is dispensable for both ALI muscle wasting and its partial mitigation by exercise in mice.<b>NEW & NOTEWORTHY</b> The endogenous glucocorticoid axis is known to influence skeletal muscle structure and function and is activated during stress. Its role in driving muscle wasting and the response to exercise in the context of lung injury is unknown. Here we find that despite a strong muscle transcriptional glucocorticoid response, this axis appears dispensable for muscle wasting or the favorable response to exercise.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E1041-E1051"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972839","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":"Low-frequency ultrasound reverses insulin resistance and diabetes-induced changes in the muscle transcriptome in aged mice.","authors":"Erik D Marchant, Ekta Singh, Sanjay Kureel, Brandon Blair, Hanna Kalenta, Zachary D Von Ruff, Korri S Weldon, Zhao Lai, Michael P Sheetz, Blake B Rasmussen","doi":"10.1152/ajpendo.00470.2024","DOIUrl":"10.1152/ajpendo.00470.2024","url":null,"abstract":"<p><p>The risk for developing insulin resistance and type II diabetes increases with age. Although lifestyle factors contribute to age-related insulin resistance, aging itself independently reduces insulin sensitivity, partially via an increase in inflammation and cellular senescence. Low-frequency ultrasound (LFU) has been shown to rejuvenate senescent cells and to reduce the proinflammatory senescence-associated secretory phenotype. Because diabetes is more common in aged individuals, there is an increased need to develop effective therapeutics for aged individuals with this condition. This study investigated the effects of LFU treatment on muscle function, blood glucose control, and skeletal muscle gene expression in aged, insulin-resistant, and diabetic mice. Insulin resistance was induced via a high-fat, high-sucrose (HFHS) diet, and diabetes was induced via an HFHS diet plus a low dose of streptozotocin. Insulin-resistant and diabetic mice exhibited impaired glucose metabolism and physical function, as well as an altered transcriptomic profile in skeletal muscle, indicating an increase in inflammation and an immune response. LFU treatment reversed much of the transcriptomic changes that occurred with insulin resistance and diabetes but had no effect on blood glucose control or physical function. LFU demonstrates potential as a noninvasive therapy for reducing inflammation and altering immune cell function in skeletal muscle in insulin-resistant and diabetic populations.<b>NEW & NOTEWORTHY</b> This study introduces low-frequency ultrasound (LFU) as a novel, noninvasive therapy that attenuates insulin resistance- and diabetes-induced transcriptional changes in aged skeletal muscle. LFU primarily reduced inflammatory and immune-related gene expression, potentially by promoting a shift toward an anti-inflammatory (M2) macrophage profile. These findings suggest that LFU may target underlying inflammatory mechanisms of insulin resistance and diabetes in aging muscle.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E899-E910"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963500","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":"<i>BRCA1</i> influences whole body metabolism in humanized mice.","authors":"Stacey Hembruff, Alexander Dekonenko, John P Thyfault, Mihaela E Sardiu, Michael P Washburn, Samuel G Mackintosh, Stephanie D Byrum, Roy A Jensen, Lisa M Harlan-Williams","doi":"10.1152/ajpendo.00222.2024","DOIUrl":"10.1152/ajpendo.00222.2024","url":null,"abstract":"<p><p>The role of <i>BRCA1</i> in cellular metabolism is not fully characterized and what we do understand has been primarily demonstrated in vitro. Our studies aimed to characterize the role of <i>BRCA1</i> in metabolic pathways in a whole body system. In vivo studies using C57BL/6 wild-type and transgenic humanized <i>BRCA1</i> mice demonstrate the effect of human <i>BRCA1</i> on the whole body metabolic phenotype and start to elucidate the mechanism by which this occurs. Promethion metabolic chambers and glucose tolerance tests measured a number of metabolic outputs of male and female mice that were either wild-type (normal mouse <i>Brca1</i> gene) or humanized <i>BRCA1</i> mice (knockout <i>Brca1</i>/knock-in human <i>BRCA1</i> gene). Humanized <i>BRCA1</i> mice are more lean, hyperactive, display higher energy expenditure, and demonstrate a sexual dimorphism in lean mass and glucose tolerance when compared with wild-type mice on the same genetic background. To begin to elucidate the mechanisms behind the observed metabolic phenotype, we performed mass spectrometry, SuperArray, and Western blot analysis using skeletal muscle, a metabolic organ that significantly impacts energy metabolism. Proteomic and genomic analysis revealed changes in a number of metabolic pathways that may be implicated in the observed whole body metabolic phenotype. We concluded that substituting <i>BRCA1</i> for <i>Brca1</i> in an in vivo model altered the overall metabolic profile of humanized <i>BRCA1</i> mice. Thus, the <i>Brca1/BRCA1</i> gene appears to have a significant impact on metabolic pathways, and these effects differ from mouse to human.<b>NEW & NOTEWORTHY</b> This is the first in vivo evidence demonstrating the complex effects of <i>BRCA1</i> expression in whole body metabolism.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E979-E993"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956245","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":"Follicular helper T cells in Graves' disease: pathogenic mechanisms and therapeutic implications.","authors":"Zhengrong Jiang, Linghong Huang, Lijun Chen, Huiyao Cai, Huibin Huang","doi":"10.1152/ajpendo.00023.2025","DOIUrl":"10.1152/ajpendo.00023.2025","url":null,"abstract":"<p><p>Graves' disease (GD) is a specific autoimmune disorder that primarily affects the thyroid gland, leading to thyrotoxicosis and potentially accompanied by extrathyroidal manifestations such as Graves' ophthalmopathy and pretibial myxedema. Its pathogenesis involves the abnormal proliferation of autoreactive B cells, which subsequently produce autoantibodies targeting the thyroid-stimulating hormone receptor (TSHR), resulting in excessive secretion of thyroid hormones. Helper T cells (Th cells) play a significant role in this process. In recent years, follicular helper T cells (Tfh cells) have been identified as a novel subset of Th cells, primarily residing in the germinal centers (GCs) of lymphoid organs and in peripheral blood. Tfh cells facilitate B cell development and antibody production, thus playing a crucial role in the pathogenesis of GD. Their aberrant proliferation and function may lead to the production of autoantibodies and pathological processes such as tissue damage. This review summarizes the latest advancements in the biology of Tfh cells and their role in GD, exploring their potential as therapeutic targets, thereby providing new insights into the pathogenesis and treatment of GD.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E952-E961"},"PeriodicalIF":4.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966609","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}