{"title":"Gut hormone secretion in a new meal tolerance test on insulin, glucagon, and glycemic excursions in patients with morbid obesity undergone sleeve gastrectomy.","authors":"Yukako Yamamoto, Masaki Kobayashi, Takeshi Togawa, Osamu Sekine, Yuki Ozamoto, Junko Fuse, Jun Ito-Kobayashi, Yasumitsu Oe, Akeo Hagiwara, Masanori Iwanishi, Akira Shimatsu, Tadahiro Kitamura, Atsunori Kashiwagi","doi":"10.1152/ajpendo.00492.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00492.2024","url":null,"abstract":"<p><p>We have reported that hypoglycemia during a 75-g oral glucose tolerance test (OGTT) in patients who underwent a laparoscopic sleeve gastrectomy (LSG) is prevented by a new mixed meal tolerance test (MTT) containing lipid, protein, and carbohydrate equivalent to 75 g glucose. We investigated whether the secretions of gut hormones including glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glicentin during OGTT involved in reactive hypoglycemia observed in post-LSG patients through changes in plasma insulin and glucagon secretions. Thus, we compared these gut hormone secretions during the OGTT and MTT in 30 Japanese patients pre- and 1-year post-LSG. Both GLP-1 and glicentin secretions were glucose-dependently stimulated in pre-LSG patients and were enhanced by the LSG. This enhancement was associated with postprandial hypoglycemia through both enhanced acute insulin secretion and suppressed glucagon secretion during the OGTT in the post-LSG patients whose calculated disposition index improved. Conversely, the MTT in the post-LSG patients attenuated the insulin secretion and fsecretion and the baseline GIP levels were positively correlated with HOMA-R in both Tg secretion and the baseline GIP levels were positively correlated with HOMA-R in both pre- and post-LSG patients. In conclusion, the glucose-induced glicentin and GLP-1 secretions were associated with glucose-induced postprandial hypoglycemia through an overstimulation of acute insulin secretion in post-LSG patients. The new MTT is useful to evaluate normalization of glucose tolerance through attenuation of glucose-stimulated glicentin and GLP-1 secretions and enhanced GIP and glucagon secretions in post-LSG patients.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140971","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":"Leptin in the VMH contributes to the initial overconsumption of palatable diets by rats.","authors":"Emily E Noble, Ruth B S Harris","doi":"10.1152/ajpendo.00090.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00090.2025","url":null,"abstract":"<p><p>Deleting leptin receptors from VMH SF1-expressing neurons exaggerates diet-induced obesity in mice. Experiments described here tested whether VMH leptin receptors prevent obesity in rats. Male, but not female, Sprague Dawley rats increased energy intake for 3 days when offered a 45% kcal fat HF diet. There was no change in body composition of either sex during 60 days of HF-feeding. Basal leptin signaling was not changed during overeating, but hindbrain leptin activity was down-regulated when HF-fed rats corrected energy intake. Male and female rats exhibited increased sensitivity to VMH leptin only during the early days of being offered HF diet. Deletion of VMH leptin receptor expressing cells using leptin-saporin (Lep-Sap) prevented the initial hyperphagia in males, but did not change subsequent energy intake, expenditure, adiposity or glucose clearance compared with rats fed 10% kcal fat diet. Surprisingly, HF-fed Lep-Sap rats responded to peripheral injection of leptin, whereas LF-fed Lep-Sap rats did not. Male Lep-Sap rats showed increased preference for 2% sucrose solution, but were more accurate than control Blank-Sap rats in compensating for consumption of a 10% sucrose solution. Similarly, Lep-Sap rats offered choice diet of lard, 30% sucrose and chow increased energy intake and body fat mass, but consumed less than Blank-Sap rats during the first 4 days on the diet by decreasing chow intake. These results suggest that VMH leptin receptors in rats contribute to the early overconsumption of palatable diets and that this is reversed when leptin signaling in the NTS and VMH are down-regulated.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140997","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}
Alessandro Brunasso, Chiara Dalla Man, Simone Poli, Jeanine J Prompers, David Herzig, Roland Kreis, Lia Bally, Michele Schiavon
{"title":"Modeling Hepatic Glucose Tracer Kinetics from Isotope Dilution Technique and Deuterium Metabolic Imaging in Post-Bariatric-Surgery and Non-Operated Individuals.","authors":"Alessandro Brunasso, Chiara Dalla Man, Simone Poli, Jeanine J Prompers, David Herzig, Roland Kreis, Lia Bally, Michele Schiavon","doi":"10.1152/ajpendo.00511.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00511.2024","url":null,"abstract":"<p><p>Despite extensive research on liver metabolism, mathematical models describing hepatic glucose kinetics are currently limited due to the lack of organ-level data. Here, we propose a model of postprandial hepatic glucose kinetics exploiting liver Deuterium Metabolic Imaging (DMI) data combined with plasma isotope dilution analysis in humans. We used data from 10 individuals who had previously undergone Roux-en-Y Gastric Bypass surgery (RYGB) and 10 healthy controls (HC). The experimental setting included a labeled Oral Glucose Tolerance Test consisting of 60g of [6,6'-<sup>2</sup>H<sub>2</sub>]-glucose in combination with liver DMI at 7T. The hepatic glucose tracer signal was frequently quantified over 150 min, while peripheral plasma insulin and glucose tracer concentrations were measured in venous blood. The model was able to describe both liver and peripheral glucose tracer data well and provided estimates of postprandial glucose appearance and disposal in both the liver and the systemic circulation. The model predicted that almost all the ingested glucose had appeared in the liver in RYGB, but not in HC (89.0% vs. 64.0%, p=0.008) after 150 min, while total hepatic disposal (RYGB=26.4% vs. HC=29.7%) and first-pass extraction (RYGB=10.7% vs. HC=11.4%) were similar between populations. The fraction of glucose eliminated in the periphery was greater in RYGB (49.9% vs. 25.3%, p=0.003). Lastly, no differences were observed in hepatic blood flow and GLUT2 transport rates. Although further studies are needed to validate and extend the model to include endogenous glucose production and disposal, it can be used to quantify parameters, and possibly reveal defects, of hepatic glucose handling.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141002","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":"Optimizing Measures of Insulin-Regulated Lipolysis in Humans.","authors":"Yilin Song, Kelli A Lytle, Michael D Jensen","doi":"10.1152/ajpendo.00078.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00078.2025","url":null,"abstract":"<p><p>The goals of these studies were to test for errors in measuring the insulin concentration resulting in 50% suppression from baseline free fatty acid palmitate rate of appearance (FFA<sub>palmitate</sub> IC<sub>50</sub>) when measured with a two-step, euglycemic, hyperinsulinemic clamp (EHC). We also determined the reproducibility of FFA<sub>palmitate</sub> IC<sub>50</sub> in weight stable adults and assessed the magnitude of the change in FFA<sub>palmitate</sub> IC<sub>50</sub>in response to weight loss. To accomplish this we analyzed data from 46 studies of 27 volunteers enrolled in two ongoing clinical research studies that included weight loss by lifestyle intervention or bariatric surgery. FFA palmitate kinetics were measure using an intravenous infusion of [U-<sup>13</sup>C]palmitate under basal (fasting) and a two-step EHC. For 40 of 46 studies, calculating FFA<sub>palmitate</sub> IC<sub>50</sub> using data from both steps of a EHC overestimated FFA<sub>palmitate</sub> IC<sub>50</sub> compared with the first (low) dose, which suppressed palmitate Ra by > 50%. FFA<sub>palmitate</sub> IC<sub>50</sub> did not change and was reproducible after 4 months (r = 0.70, P = 0.02) for 10 weight stable volunteers. Weight loss by either intervention reduced FFA<sub>palmitate</sub> IC<sub>50</sub> and the reduction was correlated with fat loss and change in adipocyte size. We conclude that, although a 2-step EHC (with an initial low dose) allows accurate assessment of FFA<sub>palmitate</sub> IC<sub>50</sub>, careful scrutiny of each set of study data is needed. These data will improve the ability of investigators to design studies that can detect small, but important differences or changes in adipose tissue insulin action.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136260","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":"https://doi.org/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 sub-analysis of our prospective observational study, subjects with obesity and T2D underwent oral glucose tolerance tests (OGTT) 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 (r=-0.49, P<0.05). In 16 subjects without severe fibrosis, changes in DI correlated with preoperative MRI-estimated proton density fat fraction (r=-0.52, P<0.05). Neither as glycemic control nor visceral fat were 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.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-16","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}
Chai-Chi Chuang Key, Lanazha Belfield, Jennifer Krall, Kevin Gibbs, Chun Liu, Lina Purcell, Renee D Stapleton, Matthew E Poynter, Michael J Toth, Matthew Quinn, Swapan K Das, D Clark Files
{"title":"Muscle wasting and the response to exercise in lung-injured mice is not primarily driven through the glucocorticoid axis.","authors":"Chai-Chi Chuang Key, Lanazha Belfield, Jennifer Krall, Kevin 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":"https://doi.org/10.1152/ajpendo.00039.2025","url":null,"abstract":"<p><p><i>Background</i>: 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. <i>Methods</i>: Intratracheal lipopolysaccharides were instilled into wild type (WT) mice. Mice exercised for prescribed intensity and duration on a treadmill. GR knockdown was achieved through pharmacologic inhibition and the use of muscle specific GR knockout mice. Muscle structure and function was evaluated using physiologic and histochemical techniques and GR activation was assessed under multiple conditions. <i>Results</i>: 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. <i>Conclusion</i>: GR signaling is dispensable for both ALI muscle wasting and its partial mitigation by exercise in mice.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Balnis, Emily L Jackson, Lisa A Drake, Catherine E Vincent, Lee Hwajeong, Harold A Singer, Ariel Jaitovich
{"title":"Chronic succinate exposure does not cause liver injury.","authors":"Joseph Balnis, Emily L Jackson, Lisa A Drake, Catherine E Vincent, Lee Hwajeong, Harold A Singer, Ariel Jaitovich","doi":"10.1152/ajpendo.00129.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00129.2025","url":null,"abstract":"<p><p>Patients with metabolic syndrome and liver dysfunction demonstrate elevated levels of succinate in the circulation. Succinate has been causally associated with non-alcoholic fatty liver disease (NAFLD) in multiple animal models and via different mechanisms including interaction with succinate receptor-1 (SUCNR-1) in hepatic stellate cells (HSCs), activity of AMP-associated protein kinase (AMPK) and others. While skeletal muscle is a major source of endogenous succinate, here, using a transgenic mouse with muscle specific ablation of succinate dehydrogenase (SDHC knockout animal) we show that sustained, long term endogenous elevation of blood succinate does not cause liver injury. Both macroscopically and histologically, livers from transgenic animals appear similar to wild-type counterparts. Moreover, tests for liver function and other biochemical serum surrogates of organ integrity; and measurements of oxygen consumption by high resolution respirometry, do not indicate evidence of succinate-induced liver toxicity in transgenic animals. This data suggests that chronically elevated endogenous succinate causes no conspicuous evidence of liver dysfunction at histological, biochemical or metabolic levels.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957251","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}
Jia-Mu Zhao, Qing Han, Chunyi Chen, Xuede Yan, Song Yu, Xian-Hua Ma, Chun-Chun Wei, Weiping J Zhang, Dongmei Cao
{"title":"Characterization of the Recombination Activity in the Pituitary and Ovary of Prop1-iCre Knockin Mice.","authors":"Jia-Mu Zhao, Qing Han, Chunyi Chen, Xuede Yan, Song Yu, Xian-Hua Ma, Chun-Chun Wei, Weiping J Zhang, Dongmei Cao","doi":"10.1152/ajpendo.00049.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00049.2025","url":null,"abstract":"<p><p>The pituitary gland plays a central role in the regulation of development, metabolism, stress, reproduction, and homeostasis in the mammalians. All the endocrine cells secreting distinct pituitary hormones are derived from Prop1-expressing progenitors. Prop1 promoter-driven Cre transgenic mice are useful in the field of pituitary biology based on the Cre/LoxP system, however their ectopic activity complexes data interpretation. Here we demonstrate the robust and specific recombination activity of a Prop1-iCre knockin line in pituitary endocrine cells as well as in ovarian granulosa cells. Prop1-iCre mice were generated by introducing IRES-Cre cassette immediately downstream of the stop codon of the <i>Prop1</i> gene by CRISPR/Cas9 system, which allows for the bicistronic expression of Prop1 and Cre recombinase simutanously. The Cre insertion had no effect on the expression of the <i>Prop1</i> gene per se or the development of pituitary endocrine cells. When crossed onto a Rosa-tdTomato reporter line, Prop1-iCre mice exhibited a robust recombination activity in all the pituitary endocrine cells, with no activity in hypothalamus, thyroid, adrenal gland, testis, heart, lung, liver, or kidney. Of note, the recombination activity was also detected in some of ovarian granulosa cells in female Prop1-iCre mice, which is consistent with their <i>Prop1</i> mRNA expression based on single-cell RNA sequencing analysis. Our findings support that the Prop1-iCre mouse line serves as a valuable tool for gene manipulation in pituitary endocrine cells, and also raise a caution regarding to its activity in the ovary.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960949","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}
Mazvita R Nyasha, Juri Tachikawa, Hikaru Komatsuzaki, Weijian Chen, Maya Onodera, Daiki Kojima, Fukie Yaoita, Makoto Kanzaki
{"title":"CEFIP-deficiency in mice enhances glucose tolerance despite compromised muscle function.","authors":"Mazvita R Nyasha, Juri Tachikawa, Hikaru Komatsuzaki, Weijian Chen, Maya Onodera, Daiki Kojima, Fukie Yaoita, Makoto Kanzaki","doi":"10.1152/ajpendo.00302.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00302.2024","url":null,"abstract":"<p><p>Mechanotransduction in skeletal muscles is crucial for promoting global physical performance by coordinating muscular strength and metabolic properties, yet the underlying mechanisms and key regulatory molecules remain poorly understood. We identified CEFIP, a Z-disc localized protein upregulated upon contractility acquisition, as a potential integrator maintaining the balance between muscular performance and glucose metabolism. CEFIP deficiency resulted in decreased physical fitness, including lower running capabilities and weaker grip strength, even with no apparent myofiber disorganization. At the molecular levels, CEFIP-deficient mice exhibited dampened expression of STARS, a key mechanosensitive factor, while FHL1 and FHL3 were upregulated, with FHL1 expression further increasing in response to exercise. Despite the overall compromised physical performance, CEFIP-deficient mice unexpectedly led to enhanced insulin responsiveness, and increased muscular AMPK phosphorylation. Moreover, CEFIP-deficient mice exhibited heightened susceptibility to an exercise load, as evidenced by PGC-1a upregulation and augmented GLUT4 regulation, and enhanced insulin sensitivity, as indicated by sarcolemmal GLUT4 translocation. Taken together, our findings suggest that CEFIP serves as a key regulatory link between exercise performance and metabolic properties, potentially through Z-disc-mediated mechanosensitive processes in exercising skeletal muscles.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962058","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}
Natascha Berger, Anna Rieder, Katharina Brugger, Bettina Amtmann, Martina Kollmann, Irmgard Oreskovic, Slave Trajanoski, Ursula Hiden, Herbert Fluhr
{"title":"Novel link between plasma bilirubin and anti-inflammatory miRNA profiles in follicular fluid of IVF patients.","authors":"Natascha Berger, Anna Rieder, Katharina Brugger, Bettina Amtmann, Martina Kollmann, Irmgard Oreskovic, Slave Trajanoski, Ursula Hiden, Herbert Fluhr","doi":"10.1152/ajpendo.00479.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00479.2024","url":null,"abstract":"<p><p>Maternal metabolic factors are increasingly recognized as critical pre-conceptional determinants of fertility outcomes. To investigate how metabolic health influences female fertility, we investigated the molecular composition of follicular fluid (FF), with a focus on microRNA (miRNA) expression. Blood and FF samples from 15 women undergoing controlled ovarian stimulation were examined in a pilot study. Clinical traits (glucometabolic markers, lipid profiles, liver function markers, inflammatory cytokines, and hormonal parameters) and oocyte outcomes were measured and recorded. Elevated plasma bilirubin levels were associated with a distinct miRNA profile in FF, characterized by an enrichment of anti-inflammatory miRNAs, including miR-146a-5p, miR-146b-5p, miR-487b-3p, and miR-21-5p. Bioinformatic analysis revealed that these miRNAs directly target key inflammatory mediators, including IL6, COX2, TLR4, IRAK1, and NFKB1, suggesting a regulatory role in intra-follicular inflammation. Furthermore, patients with a fertilization rate of ≤50% exhibited higher transcript levels of miRNAs associated with elevated plasma bilirubin. Our findings provide a novel perspective on the growing body of evidence supporting bilirubin's regulatory properties, including anti-oxidative and anti-inflammatory effects and highlight the relationship between plasma bilirubin and FF miRNA expression. The observed associations between bilirubin levels, follicular fluid miRNA composition, and oocyte quality underscore the critical influence of metabolic factors on reproductive outcomes. This exploratory work provides a foundation for further studies to investigate the functional role of plasma bilirubin in follicular physiology and its potential as a biomarker to optimize fertility treatments.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952626","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}