American journal of physiology. Endocrinology and metabolism最新文献

{"title":"The impact of maternal metabolic flexibility during gestation on infant adiposity in individuals with obesity.","authors":"Kaja Falkenhain, Nicholas T Broskey, Jasper Most, Leanne M Redman","doi":"10.1152/ajpendo.00048.2026","DOIUrl":"10.1152/ajpendo.00048.2026","url":null,"abstract":"<p><p>Maternal metabolism adapts during pregnancy to support fetal growth, yet how variability in maternal substrate oxidation influences neonatal adiposity is not well understood. Metabolic flexibility-the ability to adapt to substrate availability-may be a critical determinant of fetal nutrient supply. Therefore, the objective of this study was to examine associations between maternal metabolic flexibility and infant adiposity. Forty-seven pregnant women (28 ± 5 yr) with obesity (35.8 ± 5.8 kg/m²) were assessed in early (14.8 ± 0.7 wk) and late (35.9 ± 0.6 wk) gestation. Maternal substrate oxidation was measured overnight in a whole room indirect calorimeter. Metabolic flexibility was calculated as the difference in respiratory exchange ratio (RER) between peak postprandial RER following a standardized dinner and RER during sleep. Maternal body mass and composition were recorded at the same time points, and infant adiposity was measured within 10 days of birth by air displacement plethysmography. Maternal metabolic flexibility in late gestation was positively associated with infant birth weight [β = 169; 95% confidence interval (CI): 18-320; <i>P</i> = 0.03] and adiposity (β = 2.4; 95% CI: 0.4-4.3; <i>P</i> = 0.02), independent of gestational weight gain. Lower fasting RER was inversely associated with infant adiposity (β = -2.4; 95% CI: -4.3 to -0.4; <i>P</i> = 0.02). Postprandial RER was not predictive. Associations with infant adiposity were attenuated when birth weight was included, suggesting maternal substrate oxidation primarily influences adiposity via fetal growth. Maternal metabolic flexibility and fasting reliance on lipid oxidation in late pregnancy are key determinants of fetal growth and adiposity, highlighting the importance of maternal metabolism on developmental programming with implications for long-term offspring health.<b>NEW & NOTEWORTHY</b> This study revealed that maternal metabolic flexibility-the ability to switch between fuel sources depending on availability-and greater reliance on lipid oxidation during fasting in late pregnancy were linked to higher infant birth weight and adiposity, independent of gestational weight gain. These findings suggest that maternal substrate oxidation influences fetal nutrient supply and, consequently, growth, thereby playing a key role in shaping neonatal body composition and long-term health outcomes.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E14-E19"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004241","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":"Placental discrepancies between Black and White patients with preeclampsia in a southeastern US cohort.","authors":"Madison Ives, Gibson Cooper, Cayman Bickerstaff, Mona Elgazzaz, Cassandra Sam, Amalia Brawley, Safia Ogbi, Elisabeth Mellott, Desmond Moronge, Stephanie Stokes, Joanna Hitchings, Luis Valesquez Zarate, Sravankumar Kavuri, Padmashree C Woodham, James Maher, Jessica L Faulkner","doi":"10.1152/ajpendo.00476.2025","DOIUrl":"10.1152/ajpendo.00476.2025","url":null,"abstract":"<p><p>Preeclampsia is a devastating hypertensive disorder of pregnancy with a high prevalence in the southern regions of the United States. Black pregnant patients are disproportionally at higher risk for preeclampsia onset and severity of disease than other racial groups. The underlying mechanism(s) for this racial disparity are unclear. In our current study, we were able to obtain a cohort of patients of self-identifying Black or White race who were overall matched for body mass index (BMI), blood pressure, gestational and maternal age, and parity, and we hypothesized that placentas from Black patients with preeclampsia would demonstrate elevated preeclampsia-associated placental gene expressions compared with White patients with preeclampsia. We collected placenta tissue from both healthy individuals and preeclampsia Black and White patients (<i>n</i> = 13-17) who delivered in Augusta, GA. We measured expressions of several preeclampsia-implicated genes and performed placental morphological analysis and bulk RNA sequencing. Contrary to our hypothesis, ddPCR analysis demonstrated that leptin, preproendothelin-1 (<i>PPET-1</i>), endothelial converting enzyme-1 (<i>ECE-1</i>), and soluble FMS-like tyrosine kinase-1 (<i>sFlt-1</i>) were higher in White preeclamptic women than in Black preeclamptic women. Our RNA sequencing analysis revealed that 288 genes differed between healthy Black individuals and preeclamptic Black patients. A striking 2,394 gene expressions significantly differed between healthy and preeclamptic White patients. Placental histology analysis revealed that Black patients with preeclampsia demonstrated a lower scoring of morphological pathologies associated with preeclampsia compared with White patients with preeclampsia. Collectively, these data indicate that gene expressions and placental injury markers associated with preeclampsia are more pronouncedly elevated in White patients compared with Black patients.<b>NEW & NOTEWORTHY</b> Black patients in United States are at a discrepant high risk for preeclampsia, via mechanisms unknown. We found that White patients with preeclampsia had significantly higher changes in gene and placental morphological expressions compared with healthy pregnancy than observed in Black patients with preeclampsia. These data indicate that placental damage in preeclampsia in our cohort was less evident in Black patients with preeclampsia compared with White patients with preeclampsia and that nonplacental mechanisms for disease may be predominate in Black patients with preeclampsia.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E87-E97"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142396","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":"ATF3 in metabolic homeostasis and vascular disease: integrating bibliometric evidence with therapeutic potential.","authors":"Heng Lin, Hsi-Hsien Chen, Yu-Pei Lin, Hsiao-Fen Li, Jung-Hsuan Lin, Kuan-Han Lee, Tzu-Ling Tseng","doi":"10.1152/ajpendo.00006.2026","DOIUrl":"10.1152/ajpendo.00006.2026","url":null,"abstract":"<p><p>Activating transcription factor 3 (ATF3) functions as a central regulator of metabolic homeostasis across multiple physiological systems. A bibliometric analysis of ATF3 research (1993-2025) demonstrates an exponential growth trend, particularly in metabolic disease research, demonstrating a robust 14.15% annual growth rate, underscoring ATF3's emerging importance in metabolic regulation. This review synthesizes current knowledge of ATF3's multisystem regulatory functions, spanning endocrine, cardiovascular, nervous, immune, respiratory, digestive, and urogenital systems, and explores the molecular mechanisms by which ATF3 coordinates cellular stress responses, metabolic adaptation, and tissue-specific homeostasis. Particular emphasis is placed on ATF3's regulation of perivascular adipose tissue (PVAT) and its contribution to obesity-related vascular dysfunction. <i>Atf3</i> deficiency profoundly alters PVAT structure, adipocyte browning capacity, inflammatory signaling, and insulin sensitivity, establishing ATF3 as a critical determinant of adipose-vascular cross talk. We further evaluate emerging therapeutic strategies targeting ATF3, including natural compounds (<i>Salvia miltiorrhiza</i> derivatives and sulfuretin) and synthetic modulators (SW20.1 and ST32 series), that show promise in experimental metabolic disorders. Current challenges in therapeutic translation include achieving tissue-specific targeting and optimizing drug delivery systems. This comprehensive analysis positions ATF3 as a master regulator linking stress responses with metabolic homeostasis, highlighting its potential as a therapeutic target for obesity-related metabolic and vascular disorders.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E110-E130"},"PeriodicalIF":4.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222662","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":"Muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICU-acquired weakness.","authors":"Tom S O Jameson, Benjamin T Wall, Tomáš Urban, Adéla Krajčová, Bob Bakalář, Michal Fric, Kateřina Jiroutková, Valér Džupa, Jan Gojda, Craig Porter, Barbora Miznerová, František Duška, Francis B Stephens","doi":"10.1152/ajpendo.00022.2026","DOIUrl":"10.1152/ajpendo.00022.2026","url":null,"abstract":"<p><p>The association of perturbed skeletal muscle metabolism with intensive care unit (ICU)-acquired weakness (ICUAW) is not clear. The objective of the present study was to characterize temporal changes in skeletal muscle mitochondrial function, ATP concentration, and substrate utilization during and up to 6 mo post-ICU admission in critically ill patients, and to delineate mechanisms underpinning ICUAW by comparing the expression of genes involved in skeletal muscle mitochondrial function and substrate utilization in the critically ill patients to control groups that had either undergone elective surgery or leg immobilization (i.e., muscle disuse). The study design was a randomized controlled trial of functional electrical stimulation-assisted cycle ergometry (FESCE) versus standard care, with skeletal muscle mitochondrial respirometry defined a priori in a nested subgroup of patients as the primary outcome. Mitochondrial respirometry did not change 7 days or 6 mo after ICU admission and was not impacted by FESCE. However, a 20% reduction in muscle ATP content by <i>day 7</i> of ICU stay persisted after 6 mo and tended to associate with ICUAW (<i>P</i> = 0.078, <i>R</i>² = 0.582). Moreover, a 40% lower muscle glycogen and 2.5-fold greater muscle lactate were observed earlier at <i>day 1</i> compared with elective surgery patients. These changes reflected expression of genes related to glycogen metabolism when disuse was accounted for, and a greater expression of the gene encoding glycogen phosphorylase (PYGM) was predictive of mortality. We conclude that muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICUAW.<b>NEW & NOTEWORTHY</b> The association of skeletal muscle metabolism with intensive care unit (ICU)-acquired weakness (ICUAW) is not clear. We report for the first time that reduced muscle ATP content by <i>day 7</i> of ICU stay persisted after 6 mo and tended to be associated with ICUAW. Moreover, lower muscle glycogen and greater muscle lactate were observed earlier at <i>day 1</i> compared with elective surgery patients. These changes reflected the expression of genes related to glycogen metabolism, which were predictive of mortality.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E782-E795"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759892","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":"Undernutrition-related diabetes in mice is linked to early undernutrition.","authors":"Elvia Janeth Osorio, Zbigniew Gugala, Ichiaki Ito, Thomas Heathman, Sara M Dann, Erika Cordova, Ashanti Concepción Uscanga-Palomeque, Bruno L Travi, Peter C Melby","doi":"10.1152/ajpendo.00310.2025","DOIUrl":"10.1152/ajpendo.00310.2025","url":null,"abstract":"<p><p>The classification of undernutrition-related diabetes as a distinct entity separate from type 1 and type 2 diabetes remains under debate. Here, we show that postnatal undernutrition induces coordinated transcriptional, metabolic, and pathophysiological alterations that mediate the development of undernutrition-related diabetes in young animals. Undernourished mice exhibited hypoglycemia, reduced insulin (<i>P</i> < 0.01), and impaired glucose tolerance (<i>P</i> < 0.05), consistent with pancreatic insufficiency. Micro-computer tomography analysis revealed skeletal fragility, with significant reductions in bone mineralization (<i>P</i> < 0.01), trabecular integrity (<i>P</i> < 0.05), and increased porosity (<i>P</i> < 0.001), as commonly reported in type 1 diabetes. Liver tissue histology revealed substantial triglyceride accumulation (<i>P</i> < 0.001) and histopathological features consistent with hepatic steatosis, including hepatocyte ballooning (<i>P</i> < 0.001). RNA sequencing of liver tissue revealed a gene expression pattern hallmarked by upregulated fatty acid metabolism (<i>P</i> = 0.031) and downregulation of the PI3K/AKT/mTOR signaling pathway (<i>P</i> = 0.05). This metabolic shift was associated with <i>Pparg</i> activation (<i>Z</i> = 2.3) and increased fatty acid oxidation (<i>P</i> < 0.01). Conversely, genes involved in insulin secretion (<i>Z</i> = -3.6) and glucose metabolism (<i>Z</i> < -1.6) were downregulated. Strikingly, transitioning from early undernutrition to a standard diet for 28 days resulted in mild hyperglycemia (<i>P</i> < 0.05), accompanied by persistent hypoinsulinemia due to impaired pancreatic catch-up growth. These findings suggest that early undernutrition fosters a distinct trajectory toward insulin deficiency and undernutrition-related diabetes, while also increasing susceptibility to metabolic comorbidities. These mechanisms could serve as foundational drivers of the double burden of malnutrition, with consequences for both metabolic and skeletal health.<b>NEW & NOTEWORTHY</b> Early-life undernutrition plays a critical role in the development of undernutrition-related diabetes. Undernourished mice exhibited a metabolic shift from the glucose metabolism toward the fatty acid metabolism, leading to bone fragility and hepatic steatosis. Paradoxically, undernutrition-related diabetes emerged after transition to a regular diet due to a persistent compromised insulin production and impaired pancreatic catch-up growth. Early-life undernutrition is a pivotal contributor to metabolic disorders and comorbidities in populations facing the double burden of malnutrition.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E813-E829"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13257247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866288","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":"Correction for Boscolo et al., volume 330, 2026, p. E530-E539.","authors":"","doi":"10.1152/ajpendo.00389.2025_COR","DOIUrl":"10.1152/ajpendo.00389.2025_COR","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"330 6","pages":"E810"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142352","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":"Influence of metformin on exercise metabolism and capacity: a systematic review and meta-analysis.","authors":"Emily E Grammer, Macy E Stahl, Joaquin Ortiz de Zevallos, Craig Paterson, Arthur Weltman, Jason D Allen","doi":"10.1152/ajpendo.00012.2026","DOIUrl":"10.1152/ajpendo.00012.2026","url":null,"abstract":"<p><p>Metformin and exercise are often coprescribed in adults with prediabetes and type 2 diabetes mellitus. However, metformin may alter metabolic responses to exercise. This systematic review and meta-analysis evaluated the impact of metformin on exercise metabolism, including lactate, glucose, insulin, and free fatty acids, along with exercise capacity. Electronic databases (Web of Science, PubMed/Medline, Embase, and SPORTDiscus) were searched through January 2025. Twenty-one studies that involved acute (single dose), nonacute (multiple doses), and habitual metformin (prescribed) intake were included in the systematic review. Study quality and risk of bias were assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were conducted on lactate, glucose, insulin, and exercise capacity during acute and nonacute studies, and effects are reported as standardized mean differences (SMDs) with 95% confidence intervals. Across 325 participants (female, <i>n</i> = 125), metformin doses ranged from 500 to 3,000 mg/day and interventions ranged from 1 dose to 12 wk. Acute studies were primarily in young, healthy males, whereas habitual studies involved older adults (predominantly female) on long-term metformin treatment. Metformin was associated with greater lactate concentrations during exercise (SMD = 0.98, 95% CI: 0.36, 1.60, <i>P</i> = 0.002). Metformin modulates exercise metabolism, with the largest impact being on lactate accumulation during exercise. The direction of these interactions may depend on dose, duration, and participant characteristics. This review provides the first critical synthesis of available literature combining metformin and exercise metabolism, capacity, and training adaptations, offering insights to clinicians and exercise practitioners on potential implications of coprescribing metformin and exercise.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E842-E859"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947498","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":"Pregnancy negates thyroid hormone-induced pyrexia.","authors":"Nuria López-Alcántara, Lena Adam, Julia Resch, Susanne Keipert, Jens Mittag, Rebecca Oelkrug","doi":"10.1152/ajpendo.00569.2025","DOIUrl":"10.1152/ajpendo.00569.2025","url":null,"abstract":"<p><p>Thyroid hormone (TH) is a key regulator of body temperature; however, its role in the tightly controlled maternal thermoregulatory system that safeguards fetal viability remains unknown. To address this gap, we investigated how maternal hyperthyroidism affects thermoregulation, metabolic tissues, and endocrine signaling in pregnant C57BL/6NCrl mice. Treatment with 3,3',5-triiodo-l-thyronine (T3) from conception to late gestation initially elevated maternal core temperature, reflecting a hypothalamic pyrexic set point. However, this effect was gradually attenuated toward term, permitting the normal prepartum drop in core body temperature. Despite elevated TH levels, brown and white adipose tissues showed no thermogenic activation, whereas skeletal muscle exhibited selective metabolic remodeling, including glycogen depletion and increased mitochondrial capacity in glycolytic muscles, without changes in SERCA2 expression. Notably, maternal T3 treatment further boosted the pregnancy-associated increase in FGF21, whereas adipose tissue remained nonthermogenic, indicating a role of TH-induced FGF21 in sustaining maternal metabolic requirements. Together, these findings reveal a hierarchical adaptation in which central TH effects are overridden, peripheral thermogenic activation is partially suppressed, and endocrine signaling is redirected to maintain maternal-fetal energy balance. In summary, this study identifies a pregnancy-specific mechanism that protects the fetus from hyperthermia while sustaining maternal metabolic demands, with important implications for thyroid dysfunction and fetal programming.<b>NEW & NOTEWORTHY</b> We show that pregnancy attenuates thyroid hormone (TH)-induced pyrexia, consistent with a hierarchical adaptation. This pregnancy-specific mechanism appears to protect the fetus from maternal hyperthermia while redirecting endocrine signaling to meet maternal-fetal energy demands. Importantly, it involves a reprogramming of TH and hepatic FGF21 actions, providing new insights into maternal-fetal energy regulation and the management of thyroid dysfunction during gestation.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E796-E809"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832315","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":"Correction of hypoxemia and hypoglycemia restores muscle mitochondrial respiration and remodels mitochondrial proteome in growth-restricted sheep fetuses.","authors":"Weicheng Zhao, Daniel B Chrisenberry, Mariangel Varela, Rosa I Luna-Ramirez, Miranda J Anderson, Paul R Langlais, Laura D Brown, Sean W Limesand","doi":"10.1152/ajpendo.00073.2026","DOIUrl":"10.1152/ajpendo.00073.2026","url":null,"abstract":"<p><p>Placental insufficiency causes fetal hypoxemia and hypoglycemia and is a major driver of fetal growth restriction (FGR). In FGR skeletal muscle, mitochondrial respiration is reduced, partially due to altered mitochondrial protein abundance. We have shown that maternal oxygen and fetal glucose supplementation alleviate fetal hypoxemia and hypoglycemia and improve skeletal muscle satellite cell proliferation. However, its effects on muscle mitochondrial respiratory function and proteomic profiles remain unknown. Here, we tested whether correcting fetal hypoxemia and hypoglycemia restores mitochondrial oxidative phosphorylation and normalizes mitochondrial proteomic profiles in FGR sheep skeletal muscle. Placental insufficiency and FGR were induced by maternal hyperthermia during gestation. Near-term fetuses were chronically catheterized and received 7-10 days of maternal tracheal oxygen insufflation and fetal intravenous (IV) glucose infusion (FOG) or maternal air insufflation and fetal IV saline infusion (FAS). Both were compared with normally grown control fetuses without supplementation (CON). Principal component analysis of the mitochondrial proteome indicated that FOG clustered closer to CON than to FAS. Abundances of 48 of 80 proteins that were differentially expressed in FAS versus CON returned to CON levels with FOG supplementation. Mitochondria isolated from CON and FOG muscle had similar glutamate/malate-driven <i>state 3</i> (ADP-stimulated) respiration, and both rates were greater than FAS mitochondria. Mitochondrial complex I activity was lower in FAS compared with CON, and FOG showed an intermediate level that was not different from either group. Together, these findings indicate that prenatal oxygen and glucose supplementation rescued mitochondrial respiratory dysfunction and partially normalized mitochondrial proteome in FGR skeletal muscle.<b>NEW & NOTEWORTHY</b> Using a sheep model of placental insufficiency, we showed that prenatal oxygen and glucose supplementation improved mitochondrial respiration and partially normalized mitochondrial proteomic profiles in growth-restricted fetal skeletal muscle. These findings highlight that targeted prenatal correction of hypoxemia and hypoglycemia can mitigate mitochondrial deficits associated with fetal growth restriction.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E774-E781"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13207194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759885","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":"Acute overfeeding impairs meal-stimulated adipose tissue microvascular blood flow in healthy adults independent of changes in adiposity.","authors":"Barbara Brayner, Shaun Mason, Elmira Karimi, Michelle A Keske, Katherine M Roberts-Thomson, Lewan Parker, Andrew C Betik, Hannah J Thomas, Kimberley L Way, Katherine M Livingstone, D Lee Hamilton, Gunveen Kaur","doi":"10.1152/ajpendo.00028.2026","DOIUrl":"10.1152/ajpendo.00028.2026","url":null,"abstract":"<p><p>Subcutaneous adipose tissue microvascular blood flow (MBF) increases in response to insulin or a meal, with gastric inhibitory polypeptide (GIP) being a proposed mechanism. This vascular response is blunted in people with insulin resistance, obesity, and type 2 diabetes. The blunted MBF response is implicated in reduced nutrient delivery and increased chronic disease risk. Recently, we have shown that acute overfeeding causes hyperinsulinemia and impairs meal-induced skeletal muscle MBF in healthy people without inducing adiposity. But it is not known if acute overfeeding impacts adipose tissue MBF and plasma GIP concentrations. We studied the impact of a 7-day high-calorie high-fat (HCHF) diet intervention on body composition, postprandial plasma GIP concentrations, and truncal subcutaneous adipose tissue MBF responses to a mixed meal challenge (MMC) in healthy adults (<i>n</i> = 14). Experimental procedures were performed on <i>days 0</i> (pre-), <i>4</i> (mid-), and <i>8</i> (postintervention). Seven days of HCHF diet intervention did not change total, trunk, gynoid, android, or visceral fat. Adipose tissue MBF increased above baseline at 60 min following the MMC at pre- (<i>P</i> = 0.002) and midintervention (<i>P</i> = 0.007), but not at postintervention (<i>P</i> = 0.231). Plasma GIP concentrations significantly increased at all time points (all <i>P</i> < 0.001) from 0 to 120 min following the MMC with no differences between pre- and postintervention. In conclusion, acute overfeeding in healthy individuals leads to a blunting of meal-induced adipose tissue MBF without changes in adiposity or changes in plasma GIP. Future studies should investigate other potential mechanisms behind the HCHF diet-induced vascular impairments to prevent chronic disease risk.<b>NEW & NOTEWORTHY</b> This is the first study to investigate adipose tissue microvascular blood flow responses in healthy individuals after a short-term high-calorie high-fat (HCHF) diet intervention. We found that 7 days of HCHF diet leads to a blunting of meal-induced adipose tissue microvascular blood flow responses without any changes in adiposity or differences in fasting or postprandial circulating concentrations of gut hormone gastric inhibitory polypeptide, suggesting potentially other mechanisms are at play.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E830-E841"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939676","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}