American journal of physiology. Endocrinology and metabolism最新文献

{"title":"The GLP-1 analog, exendin-4, improves bone material properties and strength through a central relay in ovariectomized mice.","authors":"Morgane Mermet, Jessica Denom, Aleksandra Mieczkowska, Méline Wery, Emma Biggs, Fiona M Gribble, Frank Reimann, Christophe Magnan, Céline Cruciani-Guglielmacci, Guillaume Mabilleau","doi":"10.1152/ajpendo.00086.2025","DOIUrl":"10.1152/ajpendo.00086.2025","url":null,"abstract":"<p><p>Glucagon-like peptide-1 (GLP-1) has previously been shown to be indispensable for optimal bone strength by acting at the bone material level. However, it was not fully clear whether the effects of GLP-1 were mediated by direct or indirect actions on bone cells. In the present study, we were unable to demonstrate the expression of the GLP-1 receptor (GLP-1r) in bone tissue at the gene expression level using qPCR and in situ hybridization, or at the protein level. Furthermore, the peripheral administration of exendin-4, a specific GLP-1r agonist, in ovariectomized BALB/c mice enhanced postyield displacement (18%) and energy-to-fracture (24%), as well as bone volume/total volume (BV/TV) (11%), trabecular number (Tb.N) (6%), and collagen maturity (18%). These bone effects were still observed when exendin-4 was centrally administered into the lateral cerebral ventricle. On the contrary, the peripheral administration of exendin-4 coupled to bovine serum albumin, a GLP-1r agonist that cannot penetrate the brain, failed to replicate the positive effects on bone despite increased calcitonin secretion. Altogether, these data confirm that GLP-1r agonists represent an interesting approach for managing bone fragility due to ovariectomy but also suggest that GLP-1r agonists require a central relay-yet to be identified-to exert positive effects on bone physiology. Further studies are needed to decipher the mechanisms of action of GLP-1 and GLP-1r agonists on bone physiology.<b>NEW & NOTEWORTHY</b> This study discovered that medications mimicking GLP-1, like exendin-4, improve bone strength and structure in mice, including better bone volume and collagen quality. Interestingly, exendin-4's effects were observed when delivered to the brain but not when prevented from reaching it. This suggests GLP-1 influences bones through brain signals rather than acting directly on bone. Although GLP-1 treatments show promise for preventing bone weakness, more research is needed to understand this brain-bone connection.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E522-E536"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820364","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":"Distinct endothelial gene responses to acute exercise in skeletal muscle.","authors":"Adele K Addington, Rebecca M Wall, Xiaoran Wei, Sarah D Frate, Michelle L Olsen, Joshua C Drake, Siobhan M Craige","doi":"10.1152/ajpendo.00250.2025","DOIUrl":"10.1152/ajpendo.00250.2025","url":null,"abstract":"<p><p>Acute exercise causes a short-term stress, activating immediate gene expression responses. These responses are essential for cellular adaptation and resilience. Endothelial cells, positioned throughout the vasculature, play a central role in sensing and responding to these stress signals. As dynamic regulators of vascular tone, nutrient delivery, and cellular communication, endothelial cells are key integrators of metabolic adaptation. They coordinate intra- and interorgan communication through the release of signaling molecules, shaping systemic responses to exercise. Despite their importance, the endothelial cell-specific transcriptional response to exercise remains poorly understood. To interrogate the transcriptional response to exercise in endothelial cells, we used NuTRAP (Nuclear Tagging and Translating Ribosome Affinity Purification) mouse technology that expresses EGFP/L10a under control of the vascular endothelial-cadherin promoter (<i>NuTRAP^EC</i>). Following a single bout of acute exercise, ribosome-associated mRNA was isolated from endothelial cells from gastrocnemius of both exercised and sedentary animals. RNA sequencing confirmed endothelial cell-specific enrichment and revealed robust changes in gene expression. Exercise induced canonical early response genes (<i>Nr4a2</i>, <i>Sik1</i>, and <i>Slc25a25</i>) and activated pathways related to angiogenesis, oxidative stress, stress kinase signaling, vascular remodeling, and metabolic stress signaling. For context, we analyzed skeletal muscle fiber responses using NuTRAP mice driven by the human α-skeletal actin (<i>NuTRAP^SMF</i>) mice. Although some genes overlapped, skeletal muscle fiber-enriched pathways included hypoxia response and muscle development. These findings reveal a distinct microvascular endothelial transcriptional signature in skeletal muscle tissue in response to acute exercise, providing insight into the cell-type-specific mechanisms that underlie vascular adaptation and intercellular communication in response to physiological stressors like exercise.<b>NEW & NOTEWORTHY</b> This study profiles the endothelial-specific transcriptional response to acute exercise at cell-type resolution. Comparative analysis with skeletal muscle fibers revealed distinct gene expression and upstream regulators. Key findings include endothelial-specific expression of exerkines, metabolic genes, and nitric oxide signaling. These results uncover a molecular basis for endothelial adaptation to exercise and suggest a potential role in mediating systemic exercise benefits.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E560-E570"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820362","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":"Estrogen signaling is necessary for the sex difference in simulated jet lag in mice.","authors":"Maria A Venegas, Nicholas Westray, Samuel Nwadialo, Yuriko Katsumata, Julie S Pendergast","doi":"10.1152/ajpendo.00268.2025","DOIUrl":"10.1152/ajpendo.00268.2025","url":null,"abstract":"<p><p>The circadian system coordinates 24-h cycles of internal biological processes with the environmental light-dark cycle. Abrupt shifts in the timing of the light-dark cycle misalign internal circadian clocks with the environment and cause jet lag until resynchronization occurs. The objective of this study was to investigate the sex difference in simulated jet lag in mice. Female mice resynchronized faster than male mice to 6-h advances of the light-dark cycle that mimicked eastward travel. Circulating estradiol was necessary and sufficient for rapid resynchronization in female mice since ovariectomized females resynchronized slower than mice treated with estradiol. Disabling estrogen receptor α (ERα), but not estrogen receptor β (ERβ) or G-protein-coupled estrogen receptor 1 (GPER1), abolished the sex difference in resynchronization. To investigate ERα-dependent mechanisms that regulate the rate of resynchronization, we measured the endogenous circadian period and the magnitudes of phase shifts to light pulses in male and female wild-type and ERα knockout mice. Wild-type females had shorter periods and greater phase delays in response to light pulses given in the early subjective night than male mice. Disabling ERα abolished these sex differences by lengthening the circadian period and reducing the magnitudes of phase delays. Together, these data suggest that ERα alters the rate of resynchronization to shifted light-dark cycles by regulating period length and phase shift magnitude in female mice. Understanding the mechanisms underlying the sex difference in resynchronization to shifted light-dark cycles can be used to develop strategies to alleviate jet lag and circadian misalignment.<b>NEW & NOTEWORTHY</b> Coordination of circadian rhythms with environmental cycles of light and dark is critical to well-being and healthspan. Jet lag is circadian misalignment that causes fatigue, insomnia, poor mood, impaired alertness, and gastrointestinal symptoms after travel across time zones. We show there is a sex difference in simulated jet lag in mice that is regulated by ERα signaling. Our findings reveal novel mechanisms that underlie jet lag to understand and develop interventions for circadian misalignment.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E551-E559"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939019","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":"Resilience of the mitochondrial reticulum in aging.","authors":"Robert G Leija, José Pablo Vázquez-Medina, George A Brooks","doi":"10.1152/ajpendo.00110.2025","DOIUrl":"10.1152/ajpendo.00110.2025","url":null,"abstract":"<p><p>Resting and maximal exercise respiratory rates (V̇o₂) decline in aging. Those losses have been attributed to impaired mitochondrial function, but the data are inconsistent with healthy aging. To interrogate the hypothesis of mitochondrial dysregulation in aging, we studied hind limb skeletal muscles from young and older, male and female, NIA C57BL/6JN mice. We observed no age-associated changes in coupling efficiency (ADP:O) of mitochondrial reticulum preparations, but respiratory control (RCR) was decreased in older mice. In addition, older skeletal muscle exhibited subtle yet significant reductions in the expression of proteins functionally related to substrate uptake and oxidation (mMCT1, mPC1, CPT1b, and HADH). Although there were no differences in mitochondrial contents per mg of muscle in older mice, there were significant losses of muscle, and hence, mitochondrial mass and proteins associated with membrane dynamics (Drp1, Fis1, and Mfn2). Furthermore, two-dimensional and three-dimensional, cross- and longitudinal muscle sections showed alterations in mitochondrial reticulum organization in muscles of older mice. Therefore, aging is associated with subtle but significant changes in the organization and functioning of muscle mitochondrial reticulum.<b>NEW & NOTEWORTHY</b> We interrogated numerous structural and functional aspects of the mitochondrial reticulum using a standard mouse model of aging. We observed no age-associated changes in the coupling efficiency of mitochondrial preparations, but respiratory control decreased, and there were numerous subtle changes in mitochondrial morphology in aging mouse muscles. Overall mitochondrial functioning is well preserved in aging, indicating the performance decrements are related to loss of muscle mass and cardiovascular function.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E477-E494"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833645","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":"Loss of hepatocyte-specific RECK exacerbates metabolic dysfunction-associated steatohepatitis.","authors":"Ryan J Dashek, Taylor J Kelty, Rory P Cunningham, Jack Flink, Alexa A Krause, Grace Shryack, Christopher L Taylor, Grace M Meers, Tadashi Yoshida, Srinivas Mummidi, Bysani Chandrasekar, R Scott Rector","doi":"10.1152/ajpendo.00031.2025","DOIUrl":"10.1152/ajpendo.00031.2025","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) continues to be a major health crisis worldwide due to increases in obesity and insulin resistance. The role of the extracellular matrix regulator reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in metabolic liver disease is poorly understood. We previously reported that RECK gain-of-function, specifically in hepatocytes, protects against diet-induced MASH. Here, we hypothesized that hepatocyte-specific RECK loss-of-function exacerbates liver injury in a preclinical model of diet-induced MASH. Using two novel mouse models of hepatocyte-specific RECK depletion, we demonstrate that <i>RECK</i> gene deletion significantly increased inflammation, ballooning, and fibrosis in the liver. Transcriptomic and proteomic analysis supported these findings, revealing gene/protein networks associated with inflammation and fibrosis. Targeted assessment revealed that RECK depletion results in elevated hepatic mRNA levels of several genes associated with inflammation, extracellular matrix remodeling, and fibrogenesis. Furthermore, levels of phosphorylated epidermal growth factor receptor (EGFR) and its ligand amphiregulin (AREG) were also increased with RECK germline deletion, suggesting a potential link between RECK and EGFR activity. These studies reveal RECK as a critical regulator of hepatic inflammation and fibrosis and highlight its potential as a novel therapeutic in MASH.<b>NEW & NOTEWORTHY</b> Deletion of the <i>RECK</i> gene in hepatocytes induced hepatic injury in preclinical models of diet-induced MASH. Transcriptomic and proteomic analysis revealed enrichment of pathways involved in liver inflammation and fibrotic remodeling. Targeted assessment validated multi-omic findings, showing an increase in genes associated with inflammation, extracellular matrix remodeling, and fibrosis with loss of RECK. These studies reveal RECK as a critical regulator of hepatic inflammation and fibrosis and underscore its potential as novel therapeutic in MASH.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E537-E550"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783219","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":"Effects of physiological doses of atrial natriuretic peptide on lipolysis, ketogenesis, and glucose metabolism in men.","authors":"Emil List Larsen, Ulrik Ø Andersen, Gerrit van Hall, Carsten Lundby, John C Burnett, Jens P Goetze, Peter Plomgaard","doi":"10.1152/ajpendo.00341.2024","DOIUrl":"10.1152/ajpendo.00341.2024","url":null,"abstract":"<p><p>Atrial natriuretic peptide (ANP) is secreted from the heart and the circulating concentrations increases during an acute bout of exercise. ANP is suggested to stimulate lipolysis, which has been demonstrated administering supraphysiological doses of ANP to humans. However, it is not known whether an acute increase in circulating ANP within the physiological range affects lipolysis in healthy humans, and thereby play a role in mobilization of energy in healthy humans. To determine the effects of physiological doses of ANP on lipolysis, ketogenesis, and glucose metabolism in resting, healthy men. Ten healthy men were randomized to a 1-h infusion of ANP vs. placebo in a crossover design while infused with the stable isotopes: [1,1,2,3,3-D₅]-glycerol, potassium-¹³C₁₆]-palmitate, sodium-D-β-[2,4-¹³C₂]-hydroxybutyrate, and [6,6-D₂]-glucose to determine changes in rate of appearance and disappearance of glycerol, palmitate, β-hydroxybutyrate, and glucose. Plasma ANP concentration increased from 2.8 pmol/L to a peak of 11.1 pmol/L with ANP infusion. This was compiled by an increase in the plasma concentration of the secondary messenger, 3',5'-cyclic guanosine monophosphate (cGMP), from 6.5 nmol/L to 12.5 nmol/L. No effects of ANP infusion were observed in the rate of appearance and rate of disappearance of glycerol, palmitate, β-hydroxybutyrate, or glucose. The blood volume and blood pressure remained unaffected during the study. In the present study, physiological doses of ANP had no effect on lipolysis, ketogenesis, and glucose metabolism in healthy men. The lipid turn-over does, therefore, not seem to be regulated by ANP in healthy individuals.<b>NEW & NOTEWORTHY</b> Atrial natriuretic peptide (ANP) is suggested to stimulate lipolysis, which has been demonstrated using supraphysiological doses of ANP. We explored the effects of physiological doses of ANP, as observed during an acute exercise bout, on lipolysis, ketogenesis, and glucose metabolism. Ten healthy men was randomized to infusion of ANP vs. placebo using stable isotope labeled tracers. The present study indicates that lipid metabolism does not seem to be regulated by ANP in men.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E512-E521"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939067","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":"Downregulation of the mitochondrial tRNA-derived fragment mt-tRF-Leu^TAA enhances skeletal muscle insulin sensitivity.","authors":"Chris Donnelly, Véronique Menoud, Bengt Kayser, Cecile Jacovetti, Romano Regazzi","doi":"10.1152/ajpendo.00284.2025","DOIUrl":"10.1152/ajpendo.00284.2025","url":null,"abstract":"<p><p>The mitochondrial tRNA-derived fragment mt-tRF-Leu^TAA couples mitochondrial metabolism to insulin secretion. While its role in pancreatic β-cell function is well established, its broader impact on multiorgan glucose homeostasis remains unclear. In insulin target tissues, the presence, regulation, and mechanism of action of mt-tRF-Leu^TAA are entirely unexplored. This study addresses this gap by investigating the impact of diet, nutritional status, and diabetes on mt-tRF-Leu^TAA regulation and by assessing its role in insulin sensitivity. We examined mt-tRF-Leu^TAA levels in different insulin target tissues, including skeletal muscle, liver, and epididymal white adipose tissue, of rodents under physiological and pathological conditions. In skeletal muscle myotubes, we combined subcellular fractionation, antisense oligonucleotide-mediated knockdown, and glucose uptake assays to determine mt-tRF-Leu^TAA's mitochondrial localization and its influence on insulin sensitivity. mt-tRF-Leu^TAA levels in mouse skeletal muscle decreased twofold in response to fasting. In myotubes, this tRNA fragment was enriched in mitochondria, and its downregulation enhanced glucose uptake. While the levels of mt-tRF-Leu^TAA remained unchanged in insulin target tissues of diabetic mice, we observed a skeletal muscle-specific downregulation of mt-tRF-Leu^TAA in young adult rats exhibiting insulin hypersensitivity. This study identifies mt-tRF-Leu^TAA as a candidate regulator of skeletal muscle insulin response. By modulating both insulin secretion and action, mt-tRF-Leu^TAA appears to play a notable role in systemic metabolic control and may represent a promising target for diabetes treatment.<b>NEW & NOTEWORTHY</b> Fasting downregulates levels of mt-tRF-Leu^TAA in skeletal muscle. While this small RNA fragment is enriched in the mitochondria of myotubes, inhibition of mt-tRF-Leu^TAA in myotubes enhances insulin-mediated glucose uptake. Consistently, mt-tRF-Leu^TAA is also downregulated in the skeletal muscle of insulin-hypersensitive rats. Together, these findings highlight mt-tRF-Leu^TAA as a key metabolic regulator influencing both insulin secretion and action.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E571-E579"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939006","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":"Resistance training volume dictates distinct redox molecular signature in white adipose tissue: a high-sensitivity proteomics study.","authors":"Ivo Vieira de Sousa Neto, Isabelle Souza Luz, Adelino Sanchez Ramos da Silva, Wendy Assis Silveira, Muhammad Tahir, Fabiane Hiratsuka Veiga de Souza, Paulo Eduardo Narcizo de Souza, Ramires Alsamir Tibana, Bernardo Petriz, Thiago Dos Santos Rosa, Jonato Prestes, Arkadiusz Nawrocki, Martin Røssel Larsen, Wagner Fontes, Rita de Cassia Marqueti","doi":"10.1152/ajpendo.00231.2025","DOIUrl":"10.1152/ajpendo.00231.2025","url":null,"abstract":"<p><p>Although white adipose tissue (WAT) serves as a dynamic storage organ that regulates overall metabolism, the molecular impacts of resistance training (RT) on WAT are still not fully understood. Considering that training variables influence RT outcomes, understanding the relationship between exercise volume and WAT remodeling is crucial for elucidating adaptive mechanisms. The hypothesis posits that a higher volume of RT, specifically 8 wk of climbing a vertical ladder for eight sets (RT-8), will lead to more significant positive adaptations in WAT remodeling than a lower volume of four sets (RT-4). The investigation combined histological, molecular (proteomic), and biochemical analyses (electron paramagnetic resonance, zymography, and enzyme-linked immunosorbent assay) with bioinformatics tools. By high-throughput mass spectrometry-based proteomics, we quantified 4,434 proteins in WAT of male rats and revealed that the RT-8 group displayed increased protein abundance associated with lipid transport, fatty acid unsaturation, and lipolysis compared with RT-4. In addition, compared with sedentary controls, RT-8 showed enhanced antioxidant capacity through phase II antioxidant enzymes (thioredoxins, peroxiredoxins, glutathione transferases, and ferritin). In contrast, the RT-4 group did not significantly alter the redox proteome, but selectively upregulated first-line antioxidant defense via the α-Klotho/superoxide dismutase/catalase axis. RT-4 was also associated with a reduction in reactive oxygen species production (superoxide ion and hydrogen peroxide), matrix metalloproteinase-2 activity, and adipocyte cross-sectional area to a similar extent as RT-8, without disrupting redox balance, ubiquitin ligase complex activity, or inflammatory pathways. Our findings contribute to the growing body of literature, suggesting that RT volume is a key determinant of the WAT proteomic signature, with training volume eliciting distinct molecular adaptations.<b>NEW & NOTEWORTHY</b> This study is the first to analyze how resistance training (RT) volume modulates white adipose tissue (WAT) remodeling. RT decreases adiposity index and adipocyte size regardless of exercise volume. Higher-volume RT shows greater abundance linked to phase II antioxidant enzymes and lipolysis pathways. However, inflammatory mediators and redox imbalance may be related to increased volume. Conversely, lower volume induces first-line antioxidant defense through α-Klotho upregulation, revealing that each volume dictates distinct regulatory mechanisms in WAT.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E495-E511"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764372","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":"Oral glucose tolerance test-induced increases in femoral blood flow are absent in nonobese females with polycystic ovary syndrome.","authors":"Danielle E Berbrier, Will Huckins, Emily K Van Berkel, Shannon I Delage, Sarkis J Hannaian, Raychel Myara, Oluwakanyisola N Okafor, Ta Heh Chung, Togas Tulandi, Shauna L Reinblatt, Rachel N Lord, Tyler A Churchward-Venne, Charlotte W Usselman","doi":"10.1152/ajpendo.00286.2025","DOIUrl":"10.1152/ajpendo.00286.2025","url":null,"abstract":"<p><p>The oral glucose tolerance test (OGTT) promotes transient increases in peripheral blood flow via humoral mechanisms, including insulin. Polycystic ovary syndrome (PCOS) is associated with insulin resistance and vascular dysfunction, even in nonobese females. We therefore tested the hypothesis that OGTT-stimulated increases in femoral blood flow (FBF) would be impaired in females with PCOS. In the overnight postabsorptive state, plasma glucose, insulin, and FBF (duplex ultrasound and superficial femoral artery) were measured pre-OGTT and at 0, 15, 30, 60, 90, and 120 min following a 75-g glucose bolus. We recruited females with PCOS [<i>n</i> = 10, age: 27 ± 5 yr, body mass index (BMI): 23.8 ± 3.1 kg/m²] and age- and BMI-matched females without PCOS (CTRL; <i>n</i> = 10, age: 27 ± 4 yr, BMI: 23.7 ± 2.0 kg/m²). Pre-OGTT glucose concentrations were not different between PCOS and CTRL (4.7 ± 0.4 vs. 4.7 ± 0.4 mmol/L, <i>P</i> = 0.74), nor were insulin concentrations (41.7 ± 12.0 vs. 32.4 ± 11.2 pmol/L, <i>P</i> = 0.11). However, OGTT glucose area under the curve (AUC; 938 ± 124 vs. 762 ± 113 mmol/L × 120 min, <i>P</i> = 0.01) and insulin AUC (45,121 ± 16,204 vs. 27,079 ± 11,527 pmol/L × 120 min, <i>P</i> = 0.01) were higher in PCOS than CTRL. Pre-OGTT, FBF was not different between PCOS and CTRL (211 ± 50 vs. 210 ± 44 mL/min, <i>P</i> = 0.95). FBF increased across all time points postbolus in CTRL but remained unchanged in PCOS (OGTT × group, <i>P</i> < 0.01). Indeed, FBF was lower in PCOS than CTRL at 30 (224 ± 33 vs. 277 ± 48 mL/min, <i>P</i> = 0.01), 60 (227 ± 37 vs. 305 ± 48 mL/min, <i>P</i> < 0.01), 90 (217 ± 45 vs. 308 ± 64 mL/min, <i>P</i> < 0.01), and 120 min (205 ± 47 vs. 258 ± 55 mL/min, <i>P</i> = 0.04) postbolus. In sum, nonobese females with PCOS demonstrated a complete absence of OGTT-stimulated increases in peripheral artery blood flow, suggesting that PCOS is associated with profound vascular dysfunction following acute hyperglycemia.<b>NEW & NOTEWORTHY</b> To the best of our knowledge, this is the first study to demonstrate that nonobese females with polycystic ovary syndrome (PCOS) do not exhibit oral glucose tolerance test-induced increases in peripheral blood flow, unlike healthy controls. These findings highlight the peripheral vasculature as a critical and overlooked component of cardiometabolic dysfunction in PCOS, even in the absence of obesity and other cardiometabolic risk factors (e.g., hypertension and diabetes).</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E463-E476"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939022","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":"Effect of a Low Volume Exercise Intervention on the Plasma Lipidome in People with Normal Glucose, Prediabetes or Type 2 Diabetes: A Randomised Controlled Trial.","authors":"Oana C Marian, Danqing Min, Callum J Baker, Christopher John Hodgkins, James Gerofi, Xiaoyu Wang, Nathan Anthony Johnson, Anthony S Don, Stephen M Twigg","doi":"10.1152/ajpendo.00171.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00171.2025","url":null,"abstract":"<p><p>High-intensity interval training (HIIT) may improve metabolic outcomes in people with type 2 diabetes (T2D) and prediabetes (PD). This randomised controlled trial assessed plasma lipidomic differences between overweight participants (BMI>25 kg/m²) with normal glucose tolerance (NGT) (n=74), PD (n=60) or newly-diagnosed T2D (n=26), and the effects of a combined HIIT and progressive resistance training (PRT) intervention on circulating lipids. Participants were randomized to either a stretching or HIIT+PRT protocol. Fasted plasma was collected at baseline and after 12-weeks. Plasma lipids, D- and L-serine, and D- and L-alanine, were quantified with liquid chromatography-tandem mass spectrometry. Plasma lipidomics revealed significantly lower levels of sphingomyelin and lysophosphatidylcholine (LPC) and higher diacylglycerol and deoxyceramide species in T2D compared to NGT or PD. The HIIT+PRT intervention significantly reduced circulating deoxyceramides in the T2D group. We investigated the basis for elevated atypical deoxyceramides in T2D, which utilise L-alanine rather than L-serine as biosynthetic substrates. Serine levels were unchanged; however, L-alanine and D-alanine were increased in T2D. Total diacylglycerol, L-alanine and D-alanine positively correlated with fasting glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), glycated hemoglobin and liver fat, whereas sphingomyelin and LPC inversely correlated with fasting glucose and HOMA-IR. The L-alanine:L-serine ratio positively correlated with deoxyceramide levels, but was unaltered by the HIIT+PRT intervention. This study reveals plasma lipidomic perturbations in T2D, establishing that excess L-alanine may underpin elevated metabolically-adverse deoxyceramide levels in T2D, and demonstrates that a 12-week HIIT+PRT protocol significantly reduces deoxyceramides in individuals with T2D independently of the plasma L-alanine:L-serine ratio.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190633","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}