Journal of the Endocrine Society最新文献

{"title":"Ablation of PC1/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity.","authors":"Jana Moeller, Daniel T Meier","doi":"10.1210/jendso/bvae171","DOIUrl":"10.1210/jendso/bvae171","url":null,"abstract":"<p><p>Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neuropeptide and endocrine peptide precursors; it is expressed in neuroendocrine tissues as well as in immune cells. In response to endotoxemia, global PC1/3 knockout mice mount a cytokine storm and die rapidly. Further, immune cells isolated from these mice have a pro-inflammatory signature, suggesting that PC1/3 activates an unknown anti-inflammatory peptide precursor in immune cells. Here, we tested this hypothesis using tissue-specific PC1/3 ablation models. Knocking out PC1/3 in the myeloid or the hematopoietic compartment did not induce any phenotype. In contrast, proopiomelanocortin (POMC)-specific PC1/3 knockout mice phenocopied global PC1/3 knockout mice, including an enlarged spleen size and a hyperinflammatory sepsis phenotype in response to mild endotoxemia. This phenotype was prevented by steroid therapy and mimicked by blocking corticoid receptors in wild-type mice. Thus, our data suggest that sepsis hypersensitivity in PC1/3 deficiency is uncoupled from immune cell intrinsic PC1/3 expression and is driven by a lack of anti-inflammatory glucocorticoids due to an impairment in the hypothalamic-pituitary-adrenal axis.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae171"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen Exhibits a Protective Role Against Focal Erosions in Murine TNF-induced Inflammatory Arthritis.","authors":"Kiana Chen, H Mark Kenney, Edward Schwarz, Homaira Rahimi","doi":"10.1210/jendso/bvae169","DOIUrl":"10.1210/jendso/bvae169","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is characterized by erosive pathology associated with joint inflammation and a sexual dimorphism with increased prevalence in females. Here, we aim to determine whether androgen is protective against inflammatory-erosive disease in TNF-transgenic (TNF-Tg) mice. Wild-type (WT) and TNF-Tg male mice underwent sham (WT, n = 3; TNF-Tg, n = 7) or orchiectomy (WT, n = 3; TNF-Tg, n = 7) surgery at 1 month old to remove androgen production confirmed by serum testosterone concentration. Cohorts of orchiectomized TNF-Tg males were treated with either 5ɑ-dihydrotestosterone (.025 mg/day) (n = 3) or placebo (n = 3) via subcutaneous pellet insertion. Weekly clinical measures, along with mid-hindpaw bone volumes and ankle histology at 3 months old were evaluated for all groups. Orchiectomies in TNF-Tg males significantly decreased serum testosterone (<i>P</i> < .05), weight gain (<i>P</i> < .001), and mid-hindpaw bone volumes (<i>P</i> < .05) in comparison to sham TNF-Tg mice. The cuboid bone also had increased synovitis by histology with the loss of androgen (<i>P</i> < .05). Treatment of orchiectomized TNF-Tg males with 5ɑ-dihydrotestosterone protected against the changes in weight gain (<i>P</i> < .01) and bone erosion (<i>P</i> < .05) associated with decreased osteoclast number in the cuboid (<i>P</i> < .01). In the TNF-Tg model of chronic inflammatory arthritis, androgen is protective in erosive disease. The loss of endogenous androgen significantly accelerated the progression of inflammatory-erosive arthritis in male TNF-Tg mice to a similar severity as age-matched female mice. In addition, treatment with exogenous androgen prevented this observed bone loss in orchiectomized TNF-Tg males. Overall, androgen delays and limits bone erosion even in the presence of active inflammation and future studies are warranted to elucidate the associated mechanisms.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae169"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic Consultations for Endocrine Conditions: A Scoping Review.","authors":"Bahaa Abdellatif, Varun Natarajan, Alison J Leibowitz, Kailyn E Sitter, Varsha G Vimalananda","doi":"10.1210/jendso/bvae170","DOIUrl":"https://doi.org/10.1210/jendso/bvae170","url":null,"abstract":"<p><p>Electronic consultations (e-consults) are a mode of referral increasingly used to provide access to endocrine specialty care without the need for a patient in-person visit. This scoping review aimed to describe the models being used to deliver endocrine care via e-consult, what is known about outcomes of endocrine e-consult, and research gaps. The review was completed using an established methodological framework. PubMed, Embase, CINAHL, and Cochrane were searched for articles published in English between January 1, 2000, and March 21, 2024, that reported on e-consults for endocrine specialty care. The database search yielded 2522 articles, of which 19 underwent data extraction and synthesis. The overall body of endocrine e-consult literature is small and largely observational. Various models for endocrine e-consult programs exist. Findings on feasibility, acceptability, and timeliness are positive and consistent with the larger body of e-consult literature. Data on outcomes are limited but suggest that e-consults are no worse than other referral approaches to lowering A1C. Improvements in outcomes are greater for patients whose primary care providers implement e-consult recommendations. In summary, existing studies support the benefits of e-consults in various aspects of endocrine care quality, but the literature is nascent and there are significant research gaps. Future research should examine how e-consults can best address specific endocrine conditions, with a broad set of outcomes that addresses multiple quality dimensions. Advanced study designs and qualitative methods can help address unresolved questions about e-consults relevant to all specialties, including impact on care coordination and costs and best practices for reimbursement and workflow.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae170"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments.","authors":"Grant M Tinsley, Steven B Heymsfield","doi":"10.1210/jendso/bvae164","DOIUrl":"10.1210/jendso/bvae164","url":null,"abstract":"<p><p>During weight loss, reductions in body mass are commonly described using molecular body components (eg, fat mass and fat-free mass [FFM]) or tissues and organs (eg, adipose tissue and skeletal muscle). While often conflated, distinctions between body components established by different levels of the 5-level model of body composition-which partitions body mass according to the atomic, molecular, cellular, tissue/organ, or whole-body level-are essential to recall when interpreting the composition of weight loss. A contemporary area of clinical and research interest that demonstrates the importance of these concepts is the discussion surrounding body composition changes with glucagon-like peptide-1 receptor agonists (GLP-1RA), particularly in regard to changes in FFM and skeletal muscle mass. The present article emphasizes the importance of fundamental principles when interpreting body composition changes experienced during weight loss, with a particular focus on GLP-1RA drug trials. The potential for obligatory loss of FFM due to reductions in adipose tissue mass and distribution of FFM loss from distinct body tissues are also discussed. Finally, selected countermeasures to combat loss of FFM and skeletal muscle, namely resistance exercise training and increased protein intake, are presented. Collectively, these considerations may allow for enhanced clarity when conceptualizing, discussing, and seeking to influence body composition changes experienced during weight loss.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae164"},"PeriodicalIF":3.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic Activation of RFRP Neurons Reduces LH Pulse Frequency in Female but not Male Mice.","authors":"India L Sawyer, Maggie C Evans, Asha Mamgain, Caroline Decourt, Karl J Iremonger, Greg M Anderson","doi":"10.1210/jendso/bvae159","DOIUrl":"https://doi.org/10.1210/jendso/bvae159","url":null,"abstract":"<p><strong>Context: </strong>The neuropeptide RFRP-3 (RFamide-related peptide-3) is thought to play a role in the negative regulation of fertility. However, the exogenous administration of RFRP-3 yields varying results depending on the dose and route of administration, sex of the subject, and many other variables. Manipulation of in vivo neuronal activity using DREADDs (designer receptor exclusively activated by designer drugs) technology enables investigation of cell type-specific neuronal activation in a manner that better reflects endogenous neuronal activity.</p><p><strong>Objective: </strong>To test the effects of RFRP neuronal activation on pulsatile luteinizing hormone (LH) secretion.</p><p><strong>Methods: </strong>We generated mice expressing the stimulatory hM3Dq designer receptor exclusively in RFRP cells using 2 different Cre-loxP-mediated approaches: (1) we bred mice to express hM3Dq in all <i>Rfrp</i>-Cre-expressing cells, including some that transiently expressed <i>Rfrp</i>-Cre neonatally (RFRP × hM3Dq mice), and (2) we stereotaxically injected Cre-dependent hM3Dq into the dorsomedial nucleus of RFRP-Cre mice to drive hM3Dq expression exclusively in a subpopulation of adult <i>Rfrp</i>-Cre neurons (RFRP-AAV-hM3Dq mice). We then investigated the effects of acute hM3Dq activation on LH pulse frequency in RFRP × hM3Dq mice, RFRP-AAV-hM3Dq mice, and their respective controls.</p><p><strong>Results: </strong>In both female RFRP × hM3Dq and RFRP-AAV-hM3Dq mice, chemogenetic activation of Cre-driven hM3Dq led to a significant 35% to 50% reduction in LH pulse frequency compared with controls, while no differences in pulse amplitude or mean LH concentration were observed. In marked contrast, RFRP activation did not cause any changes to LH pulse dynamics in male mice.</p><p><strong>Conclusions: </strong>These data show for the first time that activation of neurons that have expressed <i>Rfrp</i>, or of a subset of adult RFRP neurons, can independently suppress LH pulsatility in female, but not male mice.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae159"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome.","authors":"Daniel A Dumesic, Melody A Rasouli, Jessica D Katz, Gwyneth G Lu, Devyani Dharanipragada, Adina F Turcu, Tristan R Grogan, Kimberly E Flores, Clara E Magyar, David H Abbott, Gregorio D Chazenbalk","doi":"10.1210/jendso/bvae162","DOIUrl":"https://doi.org/10.1210/jendso/bvae162","url":null,"abstract":"<p><strong>Context: </strong>Adipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS).</p><p><strong>Objective: </strong>To determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting: </strong>Academic center.</p><p><strong>Patients: </strong>Eighteen normal-weight PCOS women; 17 age- and BMI-matched controls.</p><p><strong>Interventions: </strong>Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy, immunohistochemistry.</p><p><strong>Main outcome measures: </strong>Clinical characteristics, hormonal concentrations, body fat distribution, SC adipose AKR1C3, AR, and AP-1 protein expression.</p><p><strong>Results: </strong>Women with PCOS had significantly higher serum androgen levels and greater android/gynoid fat mass ratios than controls. SC adipose AKR1C3, AR, and AP-1 protein expressions were comparable between the study groups, but groups differed in correlations. In PCOS women vs controls, SC adipose AKR1C3 protein expression correlated positively with android and gynoid fat masses and negatively with SC adipose AP-1 protein expression. SC adipose AR protein expression correlated negatively with fasting serum free fatty acid and high-density lipoprotein levels. In both study groups, SC adipose AKR1C3 protein expression negatively correlated with serum cortisol levels.</p><p><strong>Conclusion: </strong>In normal-weight PCOS women, SC abdominal adipose AKR1C3 protein expression, in combination with intra-adipose AP-1 and AR-dependent events, predicts fat accretion in the presence of physiological cortisol levels.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae162"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extending the Therapeutic Potential: Romosozumab in Osteoporosis Management.","authors":"Livia Liu, Roderick J Clifton-Bligh, Christian M Girgis, Matti L Gild","doi":"10.1210/jendso/bvae160","DOIUrl":"10.1210/jendso/bvae160","url":null,"abstract":"<p><p>Current therapeutic approaches for osteoporosis predominantly involve antiresorptive agents, but the emergence of bone anabolic therapy, such as romosozumab, presents a promising alternative. Romosozumab, a monoclonal antibody targeting sclerostin, exhibits both bone anabolic and antiresorptive effects, offering the potential to enhance bone mineral density and mitigate fracture risk. Evidence from several studies demonstrating the efficacy of romosozumab is now established in improving bone mineral density and reducing fracture rates in postmenopausal women and men. This review critically evaluates the role of romosozumab in osteoporosis management, emphasizing findings from real-world studies to facilitate its practical application in clinical settings. Adverse effects, comparative effectiveness with other osteoporotic agents, and challenges in sequential therapy are also discussed, providing insights for informed decision-making by physicians, particularly in the context of pre-treatment considerations. Additionally, the review examines global prescribing guidelines and highlights challenges associated with romosozumab utilization in special patient subgroups, aiming to optimize its clinical use.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae160"},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Adiposity Alterations in Postmenopausal Women With Type 2 Diabetes Are Site-Specific.","authors":"Sammy Badr, Anne Cotten, Daniela Lombardo, Stefan Ruschke, Dimitrios C Karampinos, Nassima Ramdane, Michael Genin, Julien Paccou","doi":"10.1210/jendso/bvae161","DOIUrl":"https://doi.org/10.1210/jendso/bvae161","url":null,"abstract":"<p><strong>Context: </strong>Bone marrow adiposity (BMAT) alterations in patients with type 2 diabetes mellitus (T2DM) may contribute to adverse bone effects.</p><p><strong>Objective: </strong>Characterization of BMAT content and composition in patients with well-controlled T2DM.</p><p><strong>Methods: </strong>This cross-sectional study included 2 groups of postmenopausal women: one with T2DM and the other without. The proton density fat fraction (PDFF) of the lumbar spine and proximal femur, comprising the femoral head, neck, and diaphysis, was assessed using chemical shift-based water-fat separation imaging (WFI). Magnetic resonance imaging with spectroscopy (¹H-MRS) was performed in a subgroup of participants to confirm the PDFF measurements and determine the apparent lipid unsaturation level (aLUL) at the L3 vertebrae and femoral neck. The association of imaging-based PDFFs and aLUL between diabetes groups was investigated by adjusting for confounding factors using a linear mixed model.</p><p><strong>Results: </strong>Among 199 participants, patients with T2DM (n = 29) were significantly heavier (<i>P</i> < .001) and had a higher bone mineral density (BMD) (<i>P</i> < .001 for all sites) than nondiabetic patients (n = 170). When PDFFs were compared after adjusting for age, body mass index (BMI), and BMD, the femoral head WFI-based PDFF was lower in patients with T2DM (mean [standard error] 88.0% [0.7] vs 90.6% [0.3], <i>P</i> < .001). Moreover, the aLUL at the L3 vertebrae was lower in patients with T2DM (n = 16) than in without (n = 97) (mean [standard error] 3.9% [0.1] vs 4.3% [0.1], <i>P</i> = .02).</p><p><strong>Conclusion: </strong>The content and composition of BMAT are modified in postmenopausal women with T2DM and these changes occur at specific sites.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 11","pages":"bvae161"},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Incidence of Cancers in Patients With Nonfunctional Adrenal Tumors: A Swedish Population-Based National Cohort Study.","authors":"Jekaterina Patrova, Buster Mannheimer, Martin Larsson, Jonatan D Lindh, Henrik Falhammar","doi":"10.1210/jendso/bvae154","DOIUrl":"10.1210/jendso/bvae154","url":null,"abstract":"<p><strong>Context: </strong>It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence.</p><p><strong>Objective: </strong>To analyze the cancer incidence in patients with NFAT.</p><p><strong>Methods: </strong>In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded.</p><p><strong>Results: </strong>Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors.</p><p><strong>Conclusion: </strong>The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 10","pages":"bvae154"},"PeriodicalIF":3.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Crosstalk in Multimorbidity: Identifying Compensatory Effects Among Diabetes, Hypertension, and Dyslipidemia.","authors":"Erica Pitti, Domitilla Vanni, Nicola Viceconte, Angelo Lembo, Gaetano Tanzilli, Valeria Raparelli, Greta Petrella, Daniel O Cicero","doi":"10.1210/jendso/bvae152","DOIUrl":"10.1210/jendso/bvae152","url":null,"abstract":"<p><strong>Context: </strong>Metabolomics is becoming increasingly popular for detecting markers that indicate the presence of a specific disease. However, it is usually applied to studying individual ailments, yielding results that may not be directly relevant to people with multiple health conditions.</p><p><strong>Objective: </strong>Our study proposes a different approach to explore metabolic crosstalk between various disease states.</p><p><strong>Design setting and patients: </strong>We conducted a study on subjects at medium to high risk of developing coronary artery disease. We measured the plasma levels of 83 metabolites using nuclear magnetic resonance and analyzed the connections between these metabolites and various risk factors such as diabetes, hypertension, and dyslipidemia. Linear regression and multivariate analysis were combined for this purpose.</p><p><strong>Results: </strong>Inspection of the metabolic maps created by our analysis helped us efficiently compare profiles. In this way, it was possible to discover opposing metabolic features among single conditions and their combination. Furthermore, we found compensating metabolic effects between diabetes, hypertension, and dyslipidemia involving mainly ketone body metabolism and fatty acid β-oxidation.</p><p><strong>Conclusion: </strong>Our study introduces a novel approach to investigating how metabolism reacts to the simultaneous presence of multiple health conditions. This has allowed the detection of potential compensatory effects between diabetes, hypertension, and dyslipidemia, highlighting the complexity of metabolic crosstalk in patients with comorbidities. A better understanding of metabolic crosstalk like this could aid in developing focused treatments, resulting in improved therapeutic results.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"8 10","pages":"bvae152"},"PeriodicalIF":3.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11388003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}