Journal of Endocrinology最新文献_第4页

Endocrine response in cardiogenic shock complicating myocardial infarction: the prognostic value of growth hormone and IGF-1. 心源性休克并发心肌梗死的内分泌反应：生长激素和IGF-1的预后价值。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-05-16 Print Date: 2025-06-01 DOI: 10.1530/JOE-25-0077

Priyanka Boettger, Laura Pallmann, Patrick Kellner, Isabell Schellinger, Uwe Raaz, Nils Schulz, Thomas Karrasch, Henning Lemm, Arnd Christoph, Roland Prondzinsky, Karl Werdan, Michael Buerke

{"title":"Endocrine response in cardiogenic shock complicating myocardial infarction: the prognostic value of growth hormone and IGF-1.","authors":"Priyanka Boettger, Laura Pallmann, Patrick Kellner, Isabell Schellinger, Uwe Raaz, Nils Schulz, Thomas Karrasch, Henning Lemm, Arnd Christoph, Roland Prondzinsky, Karl Werdan, Michael Buerke","doi":"10.1530/JOE-25-0077","DOIUrl":"10.1530/JOE-25-0077","url":null,"abstract":"Cardiogenic shock (CS) is a life-threatening complication of acute myocardial infarction (AMI) with high mortality. Hormonal alterations during CS may offer prognostic insights. While growth hormone (GH) dynamics have been studied in heart failure, the role of insulin-like growth factor-1 (IGF-1) in CS remains unclear. IGF-1 exerts cardioprotective effects, including reducing myocardial apoptosis after ischemia-reperfusion injury. This study examines temporal changes in GH and IGF-1 levels in CS and their prognostic value. The Halle-Cardiogenic Shock Registry included 41 AMI patients with CS. GH and IGF-1 levels were measured at admission and on day 1, 2 and 4 post-percutaneous coronary intervention. Differences were analyzed between survivors and non-survivors, as well as by age (<70 vs ≥70 years) and sex. We found that at admission, GH levels (2.86 ± 0.78 μg/L) were within the normal range in 75.6% of patients and showed no significant differences between survivors and non-survivors. IGF-1 levels (76.23 ± 5.67 μg/L) were at the lower end of normal and declined to 66.8 μg/L at 48-72 h (P = 0.14). Non-survivors had a more rapid IGF-1 decline, while survivors maintained stable levels. IGF-1 was higher in younger and male patients, while older and female patients showed a greater decline. We conclude that GH levels remained stable and lacked prognostic value, while IGF-1 decline correlated with disease severity and possible hepatic dysfunction. IGF-1 may serve as a biomarker for risk stratification and a therapeutic target for metabolic regulation and recovery in CS, warranting further investigation.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single cell resolution of neurosteroidogenesis in the murine brain: de novo biosynthesis. 小鼠脑内神经甾体生成的单细胞分解：新生生物合成。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-05-07 Print Date: 2025-06-01 DOI: 10.1530/JOE-24-0318

Prasanthi P Koganti, Vimal Selvaraj

{"title":"Single cell resolution of neurosteroidogenesis in the murine brain: de novo biosynthesis.","authors":"Prasanthi P Koganti, Vimal Selvaraj","doi":"10.1530/JOE-24-0318","DOIUrl":"10.1530/JOE-24-0318","url":null,"abstract":"Neurosteroids synthesized within the central nervous system play essential roles in modulating neurotransmission, providing neuroprotection, regulating immune responses, influencing behavior and cognition and mediating stress physiology. Despite their broad significance, the specific brain cell types capable of de novo steroid synthesis from cholesterol remain poorly defined. In this study, we analyzed single-cell transcriptomic data to map steroidogenic gene expression across cell populations in the murine brain, focusing on the de novo production of the neurosteroid pregnenolone. Our findings reveal that de novo steroidogenesis, as marked by Cyp11a1 expression, is predominantly confined to specific neuronal subtypes, particularly glutamatergic neurons of the intra- and extra-telencephalic regions and the corticothalamic layer. In contrast, Star expression, which is essential for mitochondrial cholesterol import, was more broadly distributed, occurring in both neuronal and non-neuronal cells (including oligodendrocytes, astrocytes, immune cells and vascular cells). In these non-neuronal populations, Star was notably co-expressed with mitochondrial Cyp27a1, indicative of bile acid synthesis rather than neurosteroidogenesis. This distinction highlights that Star expression alone is not a reliable marker of de novo neurosteroidogenic capacity in the brain, as its functional significance depends on the broader enzymatic context in which it occurs. The resulting single-cell map of de novo neurosteroid biosynthetic capacity across brain regions, including modest sex-associated differences, provides a foundational framework for understanding neurosteroid signaling in distinct cell types and its relevance to brain physiology and pathophysiology.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"265 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single cell resolution of neurosteroidogenesis in the murine brain: intermediary biosynthesis. 小鼠脑内神经甾体生成的单细胞分解：中间生物合成。

IF 3.9 3区医学

Journal of Endocrinology Pub Date : 2025-05-07 Print Date: 2025-06-01 DOI: 10.1530/JOE-24-0333

Prasanthi P Koganti, Vimal Selvaraj

{"title":"Single cell resolution of neurosteroidogenesis in the murine brain: intermediary biosynthesis.","authors":"Prasanthi P Koganti, Vimal Selvaraj","doi":"10.1530/JOE-24-0333","DOIUrl":"10.1530/JOE-24-0333","url":null,"abstract":"Neurosteroids synthesized within the central nervous system modulate neurotransmission, enhance neuroprotection, regulate immune responses and influence cognitive and behavioral processes. Beyond de novo synthesis of pregnenolone (PREG) from cholesterol, the brain also engages in intermediary synthesis, converting local or circulating precursors into active neurosteroids. However, the specific cell types and brain regions involved remain poorly defined. In this study, we used single-cell transcriptomic data to map the expression of steroidogenic genes and identify cell populations in the murine brain responsible for intermediary neurosteroid biosynthesis. Our findings reveal that the synthesis of bioactive steroids downstream of PREG is not streamlined but selectively compartmentalized. Notably, cells involved in de novo neurosteroid biosynthesis are largely disjointed from intermediary steps, indicating reliance on regional diffusion and/or systemic sources. Capacity for synthesis of androgens and corticosteroids anew are practically absent. While sterol sulfotransferases are expressed, sterol sulfatase required for desulfation is absent, indicating irreversible sulfonation of PREG and dehydroepiandrosterone (DHEA). Other enzymes involved in bioconversions of pregnanes and androstanes, when expressed, showed cell type- and region-specific ramifications. Although certain limitations exist in fully deciphering these results due to certain gaps in enzyme substrate specificity and isoform catalytic preferences, our study reveals valuable insights into the brain's intermediary neurosteroid pathways. The distinct compartmentalization of these processes suggests precise control over steroid regulation, which could have far-reaching functional implications. By mapping the neurosteroidogenic potential in the murine brain and sex-associated variations, this study sets the stage for future investigations into the roles of neurosteroids in brain function and their therapeutic potential in neurological disorders.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"265 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The multifaceted landscape of the StAR protein in steroid biosynthesis: from development to degeneration. 类固醇生物合成中StAR蛋白的多面景观：从发育到退化。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-04-30 Print Date: 2025-05-01 DOI: 10.1530/JOE-24-0380

Pulak R Manna

{"title":"The multifaceted landscape of the StAR protein in steroid biosynthesis: from development to degeneration.","authors":"Pulak R Manna","doi":"10.1530/JOE-24-0380","DOIUrl":"https://doi.org/10.1530/JOE-24-0380","url":null,"abstract":"Regulation of steroid hormone biosynthesis is principally mediated by the steroidogenic acute regulatory (StAR) protein and involves endocrine, autocrine and paracrine signaling in a variety of classical and non-classical tissues. Cholesterol is the precursor of all steroid hormones. The StAR protein, by mobilizing the transport of intramitochondrial cholesterol, regulates the biosynthesis of steroid hormones which play pivotal roles in diverse processes. Steroid biosynthesis is primarily mediated by mechanisms that enhance transcription, translation, or activation of StAR. These processes are primarily regulated by the cAMP/protein kinase A (PKA) pathway, in which a plethora of signaling plays permissible roles. Whereas gain-of-function of StAR, involving phosphorylation and/or acetylation, enhances the activity of StAR in optimal steroid biosynthesis; its loss-of-function, connecting mutations, markedly decreases the biosynthesis of steroid hormones. Deterioration in the steroidogenic machinery, including hormonal homeostasis, modulates immunosenescence and results in the development of various health complications and diseases. Recent advances provide evidence that aberrant expression of StAR-driven estrogen, especially 17β-estradiol (E2), biosynthesis promotes breast tumorigenesis, in which StAR is uncovered as an acetylated protein. Moreover, age-associated progressive suppression of StAR-governed sex neurosteroids influences the most prevalent neurological disorder, Alzheimer's disease, in both women and men. This review summarizes significant findings and the current understanding of the regulation of StAR in a variety of steroid-coupled events, ranging from organogenesis to carcinogenesis to neurodegeneration, and helps unravel the mechanistic insights into relevant physiological and pathophysiological implications.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"265 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteoprotective effects of lifestyle interventions against obesity-induced bone dyshomeostasis and bone loss in rats. 生活方式干预对大鼠肥胖引起的骨平衡失调和骨质流失的骨保护作用。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-04-23 Print Date: 2025-05-01 DOI: 10.1530/JOE-25-0023

Napatsorn Imerb, Patcharapong Pantiya, Chanisa Thonusin, Krittikan Chanpaisaeng, Nipon Chattipakorn, Narattaphol Charoenphandhu, Siriporn C Chattipakorn

{"title":"Osteoprotective effects of lifestyle interventions against obesity-induced bone dyshomeostasis and bone loss in rats.","authors":"Napatsorn Imerb, Patcharapong Pantiya, Chanisa Thonusin, Krittikan Chanpaisaeng, Nipon Chattipakorn, Narattaphol Charoenphandhu, Siriporn C Chattipakorn","doi":"10.1530/JOE-25-0023","DOIUrl":"10.1530/JOE-25-0023","url":null,"abstract":"Graphical abstract: Abstract: Unhealthy lifestyles and chronic metabolic stress are key contributors to obesity and the increased risk of osteoporotic fractures, both of which are significant global health concerns. This study aimed to evaluate the time-dependent effects of exercise and caloric restriction (CR) on bone homeostasis and quality in high-fat diet (HFD)-induced obesity. Seven-week-old male Wistar rats were fed either a normal diet (ND; n = 6) or an HFD (n = 30) for 28 weeks to induce obesity. At week 13, the HFD-fed rats were further divided into five groups (n = 6/group): i) HFD without intervention (HFNI), ii) 6 weeks of exercise followed by ND for 10 weeks (HFEX-S), iii) 16 weeks of continuous exercise (HFEX-L), iv) 40% CR for 6 weeks followed by a ND ad libitum for 10 weeks (HFCR-S), and v) 40% CR for 16 weeks (HFCR-L). Metabolic parameters were reassessed and samples from serum, tibia and femur were collected for analysis. Compared to ND, HFNI rats exhibited significantly elevated serum CTX-I, TRAP5b, bone malondialdehyde levels, and increased expression of p16, p21, p53, IL1-β, tnfrsf11a, tnfsf11, ctsk, fgf23 and Sost mRNA (P < 0.05). Conversely, markers of antioxidant defense (GSH-Px), Wnt signaling (Wnt1, LRP5), and bone strength were reduced (P < 0.05). Both exercise and CR improved bone parameters by reducing oxidative stress and inflammatory markers (P < 0.05). Notably, long-term exercise provided the greatest benefit by enhancing bone strength, cortical quality and trabecular microarchitecture (P < 0.05). These findings suggest that sustained lifestyle changes, particularly long-term exercise, are effective strategies for mitigating obesity-induced bone fragility.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cold aerobic exercise mitigates NAFLD fibrosis through UBAP2L-regulated TGF-β/SMAD2 signaling. 低温有氧运动通过ubap2l调控的TGFβ/Smad2信号通路减轻NAFLD纤维化。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-04-16 Print Date: 2025-05-01 DOI: 10.1530/JOE-24-0351

Jianhong Zhang, Chaoyang Li, Zhijian Rao, Xue Geng, Chen Liang, Shijie Liu, Peng Huang, Dongzhe Wu, Yiwei Feng, Jiexiu Zhao

{"title":"Cold aerobic exercise mitigates NAFLD fibrosis through UBAP2L-regulated TGF-β/SMAD2 signaling.","authors":"Jianhong Zhang, Chaoyang Li, Zhijian Rao, Xue Geng, Chen Liang, Shijie Liu, Peng Huang, Dongzhe Wu, Yiwei Feng, Jiexiu Zhao","doi":"10.1530/JOE-24-0351","DOIUrl":"10.1530/JOE-24-0351","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) can progress to fibrosis and hepatocellular carcinoma, with TGF-β playing a key role. UBAP2L regulates TGF-β expression, but its role in NAFLD remains unclear. While exercise improves NAFLD and cold exposure enhances lipid metabolism, their combined effects on NAFLD-induced fibrosis are unknown. This study examines whether exercise with cold exposure attenuates NAFLD-induced fibrosis via the UBAP2L-mediated TGF-β/SMAD2/3 pathway. Fifty 5-week-old male C57BL/6N mice were assigned to five groups: normal control (C), high-fat diet (H), high-fat diet with cold exposure (HC), high-fat diet with exercise (HE), and high-fat diet with exercise and cold exposure (HCE). After 8 weeks of a high-fat diet, the HE and HCE groups underwent treadmill exercise (50 min/session, 5 days/week for 8 weeks). H&E, Oil Red O, Masson staining, biochemical analyses, proteomics, Western blot and RT-qPCR were used to assess fibrosis-related markers. We found that body weight, liver weight, hepatic TG, TC, LDL, Glu, CHO, AST and ALT were significantly elevated in the H group. In the HCE group, hepatic TG and BUN decreased, while HDL increased. Proteomics identified UBAP2L as the most upregulated protein in the H group, but it was downregulated in the HCE group. Western blot confirmed UBAP2L overexpression in the H group and its reduction in the HCE group, with decreased α-SMA. RT-qPCR showed elevated Tgf-β, α-Sma, Smad2, Smad3, Col1a2 and Ubap2l in the H group, which were downregulated by exercise with cold exposure. Exercise with cold exposure can reduce NAFLD-induced hepatic fibrosis, probably by downregulating UBAP2L and suppressing the TGF-β/SMAD2 pathway. These suggest exercise with cold exposure may be more effective than exercise at normal temperatures in mitigating NAFLD-related fibrosis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice. GFRAL的缺失会减弱FGF21对雌性小鼠的减肥作用。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-04-15 Print Date: 2025-05-01 DOI: 10.1530/JOE-25-0017

Alberte Silke Buch-Rasmussen, Helle Andersen, Christina Stage, Ann Maria Kruse Hansen, Sarah J Paulsen, Matthew Paul Gillum, Birgitte Andersen, Anna Secher, Markus Latta, Christoffer Clemmensen, Sebastian Beck Jørgensen

{"title":"Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice.","authors":"Alberte Silke Buch-Rasmussen, Helle Andersen, Christina Stage, Ann Maria Kruse Hansen, Sarah J Paulsen, Matthew Paul Gillum, Birgitte Andersen, Anna Secher, Markus Latta, Christoffer Clemmensen, Sebastian Beck Jørgensen","doi":"10.1530/JOE-25-0017","DOIUrl":"10.1530/JOE-25-0017","url":null,"abstract":"The role of the GDF15 receptor, GDNF family receptor alpha-like (GFRAL), in the metabolic effects of FGF21 was investigated by treating female GFRAL knockout mice with recombinant human FGF21. In contrast to FGF21-treated wild-type mice, which lost 12% body weight relative to the vehicle, the absence of GFRAL coincided with a greater compensatory increase in food intake, and accordingly, the weight-lowering effect of FGF21 treatment was blunted. Interestingly, the glycemic benefits of FGF21 persisted in the absence of GFRAL. Potential crosstalk between FGF21 and GDF15 was further investigated acutely in obese male rats, in which a single dose of FGF21 did not increase endogenous circulating GDF15 levels and vice versa. Finally, overexpression of GDF15 or FGF21 with hydrodynamic gene delivery in obese male mice did not alter the expression of the other's receptor complex in regions of the hypothalamus and hindbrain. Collectively, we demonstrate an impaired weight-lowering effect of exogenous FGF21 in female GFRAL, knockout mice. Yet, further examination of the interconnectedness between the GDF15 and FGF21 endocrine axes in male rodents implies that they largely operate in parallel and are not extensively intertwined. In future studies, it will be important to investigate the influence of sex, particularly on the role of GDF15-GFRAL signaling in regulating compensatory food intake induced by FGF21 pharmacology.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of GIP, GLP-1 and GLP-2 on markers of bone turnover: a review of the gut-bone axis. GIP、GLP-1和GLP-2对骨转换标志物的影响：肠-骨轴研究综述

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-03-26 Print Date: 2025-05-01 DOI: 10.1530/JOE-24-0231

Miriam Longo, David S Mathiesen, Lærke S Gasbjerg, Katherine Esposito, Asger B Lund, Filip K Knop

{"title":"The effects of GIP, GLP-1 and GLP-2 on markers of bone turnover: a review of the gut-bone axis.","authors":"Miriam Longo, David S Mathiesen, Lærke S Gasbjerg, Katherine Esposito, Asger B Lund, Filip K Knop","doi":"10.1530/JOE-24-0231","DOIUrl":"10.1530/JOE-24-0231","url":null,"abstract":"Bone is a dynamic tissue continuously undergoing remodeling processes of resorption and formation to maintain bone mass and health. Food intake and the release of the gut-derived incretin hormones, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) and its 'sister hormone' glucagon-like peptide 2 (GLP-2), appear to regulate bone turnover processes in the postprandial state as part of the so-called gut-bone axis. The effects of these gut hormones on bone metabolism depend on their circulating concentrations. While at physiological concentrations, elicited by nutrient intake, GIP seems to be the main contributor to postprandial bone resorption; supraphysiological concentrations of gut hormones induce more potent and robust antiresorptive effects. This review provides an overview of the literature describing the role of gut-derived hormones in the regulation and maintenance of bone tissue. In addition, we describe the effects of gut hormone-based treatment modalities on bone health and discuss the potential of gut hormone-based strategies for the treatment of bone disorders in the future.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucose and energy metabolism are impaired in mice deficient for orexins. 缺乏食欲素的小鼠葡萄糖和能量代谢受损。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-03-20 Print Date: 2025-05-01 DOI: 10.1530/JOE-24-0329

Mélodie Devère, Saloua Takhlidjt, David Godefroy, Jean-Luc do Rego, Jean-Claude do Rego, Alexandre Bénani, Emmanuelle Nedelec, Nicolas Chartrel, Marie Picot

{"title":"Glucose and energy metabolism are impaired in mice deficient for orexins.","authors":"Mélodie Devère, Saloua Takhlidjt, David Godefroy, Jean-Luc do Rego, Jean-Claude do Rego, Alexandre Bénani, Emmanuelle Nedelec, Nicolas Chartrel, Marie Picot","doi":"10.1530/JOE-24-0329","DOIUrl":"10.1530/JOE-24-0329","url":null,"abstract":"Graphical abstract: Abstract: The present study aims to investigate the impact of orexin deficiency on the regulation of energy and glucose metabolism using a mouse model depleted of the prepro-orexin gene. Our data reveal that, despite a decrease in food consumption (at least in males), orexin deficiency induces a significant increase in body weight that is associated with an alteration in the body composition, as male and female orexin-deficient mice display increased fat mass compared to wild-type littermates. Nevertheless, no significant differences of global energy expenditure and locomotor activity were observed in the mutant mice relative to the control. Glucose homeostasis is also impaired in the absence of orexins, since glucose tolerance and insulin secretion are diminished, and insulin sensitivity is slightly reduced. In addition, the livers of male orexin-KO mice are significantly larger and heavier with more adipose tissue than wild-type mice. Interestingly, orexin-deficient mice present an upregulation of liver enzymes involved in gluconeogenesis and a downregulation of GCK, an enzyme that promotes glycogen storage, which may participate to the altered glucose metabolism of orexin mutant mice. To conclude, the present study indicates that orexin deficiency induces profound alterations in the regulation of energy and glucose metabolism, which is more pronounced in males than in females. These findings support the idea that dysfunction of this orexin system may promote obesity and diabetes, and could represent an interesting therapeutic target in the context of 'diabesity'.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TEDML: a new machine learning (ML) approach for predicting thyroid eye disease and identifying key biomarkers. TEDML：一种新的机器学习（ML）方法，用于预测甲状腺眼病和识别关键生物标志物。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-03-14 Print Date: 2025-05-01 DOI: 10.1530/JOE-24-0362

Jing Zhu, Shu Zhu, Bin Liu, Xin Zheng, Xiaofei Yin, Lingling Pu, Jing Yang

{"title":"TEDML: a new machine learning (ML) approach for predicting thyroid eye disease and identifying key biomarkers.","authors":"Jing Zhu, Shu Zhu, Bin Liu, Xin Zheng, Xiaofei Yin, Lingling Pu, Jing Yang","doi":"10.1530/JOE-24-0362","DOIUrl":"10.1530/JOE-24-0362","url":null,"abstract":"Thyroid eye disease (TED) features immune infiltration and metabolic dysregulation. Understanding these processes and identifying potential biomarkers are crucial for improving diagnosis and treatment. To this end, immune cell infiltration was analyzed and gene set variation analysis (GSVA) was conducted on the GSE58331 dataset to identify differences between TED and normal tissues. Differentially expressed genes were identified using GSE58331 and GSE105149. Subsequently, a prediction model (TEDML) was developed by combining 113 machine learning algorithms to identify key biomarkers. In addition, enrichment analyses were performed to understand biological functions and pathways involved in TED, and drug sensitivity analyses were conducted to identify potential therapeutic agents. Immune infiltration analysis revealed higher levels of CD4+ Tem, CD4+ Tcm, NKT, NK cells and neutrophils in TED patients compared to controls, with lower levels of macrophages M1 and M2. GSVA indicated significant enrichment in immune-related processes and metabolic pathways. The TEDML model, constructed from the Stepglm[forward] algorithm, demonstrated high accuracy (area under curve of 1 on the training set, 0.893 in validation set), identifying six key genes (CSF3R, ALDH1A1, MXRA5, VSIG4, DPP4 and MDH1). Drug sensitivity analysis suggested that azathioprine and methylprednisolone might be effective at different stages of TED, with CSF3R as a potential therapeutic target. Overall, the TEDML model is accurate and reliable, and the identification of CSF3R as a key biomarker and its correlation with drug sensitivity offers new insights into targeted therapy for TED.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0