American journal of physiology. Endocrinology and metabolism最新文献

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Alpha cells transdifferentiate into delta cells during the progression of autoimmunity in non-diabetic NOD mice. 在非糖尿病NOD小鼠自身免疫过程中,α细胞向δ细胞转分化。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-26 DOI: 10.1152/ajpendo.00193.2025
Zhehui Li, Xinyun Wu, Qi Kang, Qi Ren, Yi Zhang, Quanwen Jin, F Susan Wong, Mingyu Li
{"title":"Alpha cells transdifferentiate into delta cells during the progression of autoimmunity in non-diabetic NOD mice.","authors":"Zhehui Li, Xinyun Wu, Qi Kang, Qi Ren, Yi Zhang, Quanwen Jin, F Susan Wong, Mingyu Li","doi":"10.1152/ajpendo.00193.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00193.2025","url":null,"abstract":"<p><p>The incidence of Type 1 diabetes (T1D) has increased in recent years. Although extensive research has focused on immune damage to insulin-producing beta cells, the pathophysiological effects on other endocrine cells within pancreatic islets remain less well-documented. This study investigates the changes in the number and proportion of alpha-, beta- and delta- cells, as well as hormone secretion, during the progression of autoimmunity in non-diabetic non-obese diabetic (NOD) mice at different ages. Our findings reveal significant heterogeneity in islet size, endocrine cell composition and degree of immune infiltration. We propose a novel classification system for islet subtypes based on this observed heterogeneity. Notably, we noticed an age-related increase in delta cells in older non-diabetic NOD mice. Additionally, we observed an increase in glucagon and somatostatin double-positive cells following immune cell infiltration in non-diabetic mice. Our further analysis demonstrated that these double-positive cells represent a transdifferentiation process from alpha cells to delta cells, mediated by an alpha-cell dedifferentiation intermediate. Moreover, our results indicated that the increased presence of delta cells and somatostatin in pancreatic islets significantly inhibits alpha cell function during the progression of autoimmunity. Thus, our findings provide valuable insights into the dynamic changes in alpha and delta cells throughout the natural history of T1D.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172266","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}
引用次数: 0
Plasma and fecal bile acids profiles in metabolic dysfunction-associated steatotic liver disease with advanced fibrosis. 代谢功能障碍相关脂肪变性肝病伴晚期纤维化的血浆和粪便胆汁酸谱
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-23 DOI: 10.1152/ajpendo.00346.2024
Marion Pradeau, Sandrine Beaulieu, Véronique Paquet, Jocelyn Trottier, Mélanie Verreault, Stéphanie Ferland, Olivier Barbier, Anne-Marie Carreau
{"title":"Plasma and fecal bile acids profiles in metabolic dysfunction-associated steatotic liver disease with advanced fibrosis.","authors":"Marion Pradeau, Sandrine Beaulieu, Véronique Paquet, Jocelyn Trottier, Mélanie Verreault, Stéphanie Ferland, Olivier Barbier, Anne-Marie Carreau","doi":"10.1152/ajpendo.00346.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00346.2024","url":null,"abstract":"<p><p>Bile acids (BAs) act as hormonal ligands of hepatic and intestinal receptor FXR, stimulators of FGF-19 and GLP-1 secretion. While MASLD is linked to BA dysregulation, the effects of advanced fibrosis on plasma and fecal BA profiles remain unclear. We compared 35 plasmatic and fecal BA concentrations and qualitative pools, including primary, secondary, unconjugated and conjugated BAs in fasting state between individuals with advanced fibrosis stages (F3-F4/4) (n=28) and individuals without advanced fibrosis (n=26). Median age (IQR) (56 [48-65] vs 57 [49-66] yr), sex (62 vs 60% man) and BMI (32 [29-36] vs 34[32-38] kg/m<sub>2</sub>) were comparable between groups. Total plasmatic BA concentration was increased in the advanced stage of fibrosis (p<0.01), whereas total stool BA concentration did not differ between groups (p = 0.36). Participants with advanced fibrosis had higher CDCA family BAs, which was driven by increased glyco- and tauro-conjugated forms (p<0.05). Plasma unconjugated secondary BA LCA was also higher in advanced fibrosis (p<0.01), but we did not find change in intestinal microbiota BSH enzymatic activity, responsible for deconjugation of BA. There were no differences in FGF-19 and GLP-1 concentrations between groups. Overall, our results lead us to hypothesize that the increase in hepatic bile acid production in cases of MASLD with advanced fibrosis may occur mainly via the acid pathway, or leakage of BAs from the liver into the plasma caused by hepatic inflammation, without changes in intestinal BA metabolism. This profile of increased hydrophobic plasma BA may contribute to MASLD progression, inflammation and oxidative stress.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129812","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}
引用次数: 0
Obesity versus Endurance Exercise Training: Plasma Triacylglycerol and Muscle Lipoprotein Lipase Activity at the Crossroads of Lipid Accumulation in Muscle. 肥胖与耐力运动训练:血浆三酰甘油和肌肉脂蛋白脂肪酶活性在肌肉脂质积累的十字路口。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-22 DOI: 10.1152/ajpendo.00162.2025
Kailin Johnsson, Jessica G George, Elizabeth J Parks, Christos S Katsanos
{"title":"Obesity versus Endurance Exercise Training: Plasma Triacylglycerol and Muscle Lipoprotein Lipase Activity at the Crossroads of Lipid Accumulation in Muscle.","authors":"Kailin Johnsson, Jessica G George, Elizabeth J Parks, Christos S Katsanos","doi":"10.1152/ajpendo.00162.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00162.2025","url":null,"abstract":"<p><p>Individuals with obesity and endurance exercise-trained athletes both exhibit excess lipid content in their skeletal muscle compared to healthy, sedentary individuals, yet they experience vastly different health outcomes. Lipids taken up from the circulation contribute to lipid stored in muscle in both populations. Differences in the muscle uptake of plasma non-esterified fatty acids (NEFA) and fatty acids derived from plasma triacylglycerol (TG) between individuals with obesity and endurance-trained athletes have not been systematically examined. In athletes, muscle actively regulates the uptake of TG-derived fatty acids through upregulation of the activity of muscle lipoprotein lipase - the enzyme responsible for the intravascular hydrolysis of TG, a phenomenon evident in the fasting state. In contrast, in individuals with obesity, skeletal muscle functions as a passive recipient of TG-derived fatty acids, an event that becomes quantitively more important when the plasma TG concentrations increase during the postprandial state. Considerable differences in the muscle uptake of plasma NEFA between athletes and individuals with obesity are less evident. These observations indicate mechanistic differences in the regulation of plasma TG-derived fatty acids uptake in muscle between individuals with obesity and endurance-trained athletes in shaping the excess lipid content in their muscles. Moreover, this evidence highlights the need for targeting a reduction in plasma TG in the postprandial state when aiming to attenuate lipid accumulation in muscle in the pathophysiology of obesity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123986","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}
引用次数: 0
AQP1- A regulatory factor associated with brown adipose tissue-silencing to combat obesity and metabolic disease. AQP1-一种与棕色脂肪组织沉默相关的调节因子,可对抗肥胖和代谢疾病。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-22 DOI: 10.1152/ajpendo.00380.2024
Chloe Cheng, Christopher Blay, Pei-Yin Tsai, Muying Li, Matthew Williams, Noel Acor, Kaydine Edwards, Yue Qu, Yang Liu, Leah D'Silva, Nina Buettner, Claire Walter, Mary Snyder, Ines Pd Costa, Olivier Devuyst, Joeva Barrow
{"title":"AQP1- A regulatory factor associated with brown adipose tissue-silencing to combat obesity and metabolic disease.","authors":"Chloe Cheng, Christopher Blay, Pei-Yin Tsai, Muying Li, Matthew Williams, Noel Acor, Kaydine Edwards, Yue Qu, Yang Liu, Leah D'Silva, Nina Buettner, Claire Walter, Mary Snyder, Ines Pd Costa, Olivier Devuyst, Joeva Barrow","doi":"10.1152/ajpendo.00380.2024","DOIUrl":"https://doi.org/10.1152/ajpendo.00380.2024","url":null,"abstract":"<p><p>The activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) by environmental cold challenge yields strong metabolic benefit in the face of diet-induced obesity (DIO). Yet, a critical barrier to leveraging brown fat NST for therapeutic use against metabolic disease is that BAT is silenced and inactive at physiological ambient temperature conditions in humans. The mechanisms that govern this silencing process remain poorly understood. Here, we identified a putative BAT-silencing factor, aquaporin-1 (AQP1), in brown fat from wild-type (WT) mice via proteomics analysis. We generated the first BAT-specific AQP1 knockout mice (AQP1-KO) and revealed that AQP1-KO could activate NST under BAT silencing environmental conditions and that the AQP1-KO mice were significantly protected against DIO and metabolic dysfunction compared to Flox controls. We found that AQP1-KO mice on high fat diet (HFD) had reduced weight gain through reductions in fat mass, improved glucose tolerance, and increased whole body energy expenditure compared to Flox control mice. Mechanistically, we show that AQP1 ablation in mice had upregulated gene expression related to the electron transport chain (ETC) and mitochondrial translation contributing to the activation of NST under BAT environmental silenced conditions.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124011","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}
引用次数: 0
Measuring associations between hormonal entropy, the prevalence of vasomotor symptoms, and menstrual dynamics. 测量激素熵、血管舒缩症状的普遍性和月经动态之间的关联。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-22 DOI: 10.1152/ajpendo.00083.2025
J F Winkles, Nanette Santoro, Mary D Sammel, Samar R El Khoudary, Alicia Colvin, Sybil Crawford
{"title":"Measuring associations between hormonal entropy, the prevalence of vasomotor symptoms, and menstrual dynamics.","authors":"J F Winkles, Nanette Santoro, Mary D Sammel, Samar R El Khoudary, Alicia Colvin, Sybil Crawford","doi":"10.1152/ajpendo.00083.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00083.2025","url":null,"abstract":"<p><p>This study investigates whether deviations in the regularity/complexity of urinary sex hormones relative to textbook 'gold standard' (GS) menstrual cycle patterns are associated with vasomotor symptom (VMS) occurrence and how these relationships might relate to differences in hormonal profiles. 549 midlife women provided daily urine-based measurements of follicle-stimulating hormone (FSH), estrogen conjugates (E1C), pregnanediol glucuronide (PDG), and luteinizing hormone (LH) over a complete menstrual cycle. Distribution and fuzzy entropy (DistEn, FuzzEn) were used to gauge hormone regularity/complexity, emphasizing structural complexity and temporal unpredictability respectively. Entropy metrics were classified as being elevated or lowered relative to the GS and then evaluated in relation to VMS prevalence. These same entropy classifications were used to evaluate hormone profiles by referencing 11 dynamics indicative of normal or reproductively aging cycles. Elevated entropy was positively associated with the likelihood of VMS for PDG-DistEn and E1C-DistEn and negatively associated for PDG-FuzzEn, E1C-FuzzEn, and LH-FuzzEn. Lowered entropy was negatively associated with VMS likelihood for LH-FuzzEn and PDG-FuzzEn and positively associated for FSH-FuzzEn and E1C-DistEn. Entropy analysis provides useful insight into menstrual cycle dynamics and their associations with VMS. Specifically, entropy can identify different underlying states of hormonal dysregulation associated with increased VMS occurrence, potentially providing insights into VMS causes and treatments. Furthermore, entropy metrics for PDG show potential in gauging degrees of reproductive aging, which could help in addressing health risks associated with late/early menopause. Finally, entropy may contribute towards efforts in understanding how a woman's VMS experience will progress through the menopause transition.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123990","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}
引用次数: 0
RELATIONSHIP BETWEEN MATERNAL OBESITY, BIRTH WEIGHT AND FETAL ADIPONECTIN/LEPTIN RATIO: A POTENTIAL EARLY BIOMARKER OF CARDIOMETABOLIC RISK. 母亲肥胖、出生体重和胎儿脂联素/瘦素比值的关系:心脏代谢风险的潜在早期生物标志物
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-17 DOI: 10.1152/ajpendo.00259.2025
Juliana Pereira Morais, Débora Veiga, Ana Filipa da Silva Ferreira, Maria Inês Nuno Alves, Inês Castela, Carla Maria de Almeida Ramalho, Joana Miranda, Adelino Leite-Moreira, Inês Falcão-Pires
{"title":"RELATIONSHIP BETWEEN MATERNAL OBESITY, BIRTH WEIGHT AND FETAL ADIPONECTIN/LEPTIN RATIO: A POTENTIAL EARLY BIOMARKER OF CARDIOMETABOLIC RISK.","authors":"Juliana Pereira Morais, Débora Veiga, Ana Filipa da Silva Ferreira, Maria Inês Nuno Alves, Inês Castela, Carla Maria de Almeida Ramalho, Joana Miranda, Adelino Leite-Moreira, Inês Falcão-Pires","doi":"10.1152/ajpendo.00259.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00259.2025","url":null,"abstract":"<p><p>Adiponectin and leptin are key adipokines that play crucial roles in metabolic regulation and in fetal and neonatal growth. In adults, lower adiponectin/leptin ratio (AdipoQ/Lep) has been suggested as a potential biomarker for metabolic risk. This study aimed to investigate whether the AdipoQ/Lep ratio in fetal blood correlates with the maternal and neonatal phenotypes and whether it holds predictive value for the cardiometabolic risk of the offspring in early life. Umbilical cord blood (UBC) samples were collected at birth, and the concentrations of adiponectin and leptin levels were measured using ELISA kits. Infants were evaluated echocardiographically at 5±2 months-old (range: 1-12 months) and these parameters were correlated with the AdipoQ/Lep levels. Results show that fetal AdipoQ/Lep ratio was lower in infants born to mothers with prepregnancy obesity. Both prepregnancy weight and maternal weight at the end of the gestation correlated with the AdipoQ/Lep ratio in UBC, whereas gestational weight gain showed no such association. Additionally, birth weight, birth length and BMI-for-age Z-score were negatively correlated with the AdipoQ/Lep ratio. Notably, lower levels of this adipokine-based biomarker were associated with reduced Z-score of left ventricular end-diastolic diameter. However, multiple linear regression analysis showed that maternal obesity and somatometry at birth influence infants' cardiac function and structure, independent of UBC AdipoQ/Lep ratio, adiponectin or leptin alone. To our knowledge, this is the first investigation to explore the relationship between fetal AdipoQ/Lep levels, maternal-neonatal weight, and early cardiac alterations, highlighting the biomarker's potential predictive value for early-life cardiometabolic risk.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079469","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}
引用次数: 0
Concentrations of Adrenocorticotropic Hormone (ACTH1-24) Too Low to Effect Cortisol Enhance Osteogenesis In Vitro and In Vivo. 促肾上腺皮质激素(ACTH1-24)浓度过低而不影响皮质醇在体外和体内促进成骨。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-12 DOI: 10.1152/ajpendo.00084.2025
Irina L Tourkova, Reed A Rankin, Quitterie C Larrouture, Steve F Dobrowolski, Carlos M Isales, Harry C Blair
{"title":"Concentrations of Adrenocorticotropic Hormone (ACTH<sub>1-24</sub>) Too Low to Effect Cortisol Enhance Osteogenesis <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Irina L Tourkova, Reed A Rankin, Quitterie C Larrouture, Steve F Dobrowolski, Carlos M Isales, Harry C Blair","doi":"10.1152/ajpendo.00084.2025","DOIUrl":"10.1152/ajpendo.00084.2025","url":null,"abstract":"<p><p>After finding that minimal amounts of adrenocorticotropic hormone (ACTH<sub>1-24</sub>) prevented osteonecrosis in rabbits, we studied bone formation at nanomolar ACTH<sub>1-24</sub>, <i>in vivo</i> in rabbits, and <i>in vitro</i> in human osteoblasts. ACTH<sub>1-24</sub> in rabbits at 0.6 μg/kg/day had no measurable effect on cortisol. Groups of five rabbits given 0.6 μg/kg/day of ACTH<sub>1-24</sub> enhanced trabecular bone in the rabbit femoral head relative to saline-treated controls (controls), increased bone volume/total volume (BV/TV) by micro-computed tomography, p<0.03. Xylenol orange and calcein labeling <i>in vivo</i> showed increased trabecular bone formation with 0.6 μg/kg/day of ACTH<sub>1-24</sub>, p = 0.0089 versus controls. In contrast, the cortex of the femoral shaft was unaffected, BV/TV p>0.95 ACTH<sub>1-24</sub> versus controls. Bone marrow mRNA by PCR showed no change in osteoclast markers, and confirmed increased osteoblast markers, p<0.05. <i>In vitro</i>, ACTH<sub>1-24</sub> elevated expression of Collagen 1, alkaline phosphatase (ALP), osteocalcin (BGLAP), and RunX2 in human osteoblasts differentiated on polyethylene terephthalate (PET) membranes. Optimal response was at 10<sup>-9</sup> to 10<sup>-12</sup> M. VEGF, VEGF receptors FLT-1 and FLK-1, and ACTH<sub>1-24</sub> receptors MC2R were upregulated at 10<sup>-12</sup> M ACTH<sub>1-24</sub>. Pathway analysis included increased BMP2, Smad1, Wnt-1, β-Catenin and TGF-β pathways. Because bone-forming osteoblasts are metabolically highly active, we studied mRNA expression of mitochondrial complex 1 (NDUFA5, NDUFS2, NDUFB1, NDUFB6) members with key roles in energy production. This increased at 10<sup>-12</sup> M ACTH<sub>1-24</sub>. An ELISA for mitochondrial complex 1 activity showed maximum activity at 10<sup>-9</sup> M and high activity at 10<sup>-12</sup> M ACTH<sub>1-24</sub>. Thus, long-term very low dose ACTH<sub>1-24</sub> increases bone formation <i>in vivo</i> and <i>in vitro</i>.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051542","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}
引用次数: 0
Supplementation with GPR120 (Ffar4) ligand omega-3 does not improve survival in murine sepsis models. 补充GPR120 (Ffar4)配体omega-3并不能提高小鼠脓毒症模型的存活率。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-12 DOI: 10.1152/ajpendo.00147.2025
Susana Castelo Branco Ramos Nakandakari, Eric Isaac Elliott, Renan Fudoli Lins Vieira, Thaiane da Silva Rios, Andin Fosam, Isadora Carolina Betim Pavan, Maíra Maftoum Costa, Luiz Guilherme Salvino da Silva, Camila de Oliveira Ramos, Giovana Rios Gonçalves, Ngozi D Akingbesote, Davi Sidarta-Oliveira, Ana Paula Moreli, Renata Rosseto Braga, Ana Paula Pinto, Anna Eisenstein, Licio Augusto Velloso, Fernando Moreira Simabuco, José Rodrigo Pauli, Eduardo Rochete Ropelle, Adelino Sanchez Ramos da Silva, Andrew Wang, Rachel J Perry, Dennys Esper Cintra
{"title":"Supplementation with GPR120 (Ffar4) ligand omega-3 does not improve survival in murine sepsis models.","authors":"Susana Castelo Branco Ramos Nakandakari, Eric Isaac Elliott, Renan Fudoli Lins Vieira, Thaiane da Silva Rios, Andin Fosam, Isadora Carolina Betim Pavan, Maíra Maftoum Costa, Luiz Guilherme Salvino da Silva, Camila de Oliveira Ramos, Giovana Rios Gonçalves, Ngozi D Akingbesote, Davi Sidarta-Oliveira, Ana Paula Moreli, Renata Rosseto Braga, Ana Paula Pinto, Anna Eisenstein, Licio Augusto Velloso, Fernando Moreira Simabuco, José Rodrigo Pauli, Eduardo Rochete Ropelle, Adelino Sanchez Ramos da Silva, Andrew Wang, Rachel J Perry, Dennys Esper Cintra","doi":"10.1152/ajpendo.00147.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00147.2025","url":null,"abstract":"<p><p>Sepsis is a condition marked by physiologic dysregulation secondary to infection and is influenced by the nutritional state. Despite several preclinical studies and clinical trials examining nutrition and supplements in sepsis, there are no clear guidelines. Omega-3 fatty acids are poly-unsaturated fatty acids with anti-inflammatory properties, represented mainly by alpha-linolenic (ALA - C18:3), eicosapentaenoic (EPA - C20:5), and docosahexaenoic (DHA - C22:6). Since sepsis is characterized with high levels of inflammation and subsequent organ dysfunction, we hypothesised that omega-3 ingestion would improve sepsis survival by attenuating inflammation via activation of GPR120 in immune cells. Here, we aimed to experimentally explore the role of omega-3 and the receptor that mediates their anti-inflammatory functions, GPR120, during sepsis. To evaluate GPR120 functionality, acute inflammation was induced via lipopolysaccharide (LPS) treatment in Raw 264.7 cells, 3T3-L1 cells, bone marrow derived macrophages and primary adipocytes. To evaluate the impact of omega-3 in sepsis, C57BL/6J mice were supplemented with omega-3 before LPS administration or cecal ligation and puncture (CLP) surgery. GPR120 mRNA expression decreased during inflammation. Unexpectedly, omega-3 supplementation preceding CLP worsened sepsis survival in mice. In addition, omega-3 did not affect inflammatory markers such as TNFα, IL1}, IL10, and IL6. Overall, our findings that omega-3 do not influence inflammation or improve survival in sepsis are surprising given that omega-3 supplementation is recommended for the prevention of cardiovascular diseases due to its anti-inflammatory properties. The negative impact of omega-3 supplementation on survival in the CLP model raises caution for future clinical studies involving sepsis.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051581","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}
引用次数: 0
Replicating human diabetes: insights from a novel animal model. 复制人类糖尿病:来自一种新型动物模型的见解。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-12 DOI: 10.1152/ajpendo.00226.2025
Silvia Teixidó-Trujillo, Esteban Porrini, Luis Manuel Menéndez-Quintanal, Armando Torres-Ramírez, Cecilia Fumero, Ana E Rodríguez-Rodríguez
{"title":"Replicating human diabetes: insights from a novel animal model.","authors":"Silvia Teixidó-Trujillo, Esteban Porrini, Luis Manuel Menéndez-Quintanal, Armando Torres-Ramírez, Cecilia Fumero, Ana E Rodríguez-Rodríguez","doi":"10.1152/ajpendo.00226.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00226.2025","url":null,"abstract":"<p><p>Type 2 diabetes is considered the pandemic of the 21st century. The pathogenesis of diabetes is complex and multifactorial, and its understanding is crucial for its prevention and treatment. Nevertheless, the pathogenesis of beta cell dysfunction remains unclear. This gap in knowledge could be related to a lack of appropriate pre-clinical models of type 2 diabetes. Current animal models, mostly genotypic and monogenic, do not fully reflect the pathophysiology of type 2 diabetes or associated organ damage. Therefore, a new pre-clinical model is needed. In this study we present a non-genotypic animal model of diabetes that combines obesity and the treatment with the diabetogenic immunosuppressor Tacrolimus (TAC). Sprague Dawley male rats were fed with a high-fat diet to establish obesity and metabolic syndrome. Then, TAC was administered for 6-9 months to induce chronic hyperglycaemia. These animals showed a decrease in Langerhans islets area and number, and development of islet fibrosis. There were also changes in pancreatic insulin and glucagon content, imbalance in the alpha/beta cell ratio and decrease in the expression of essential transcription factors MafA, FOXO1A, PDX-1 and NeuroD1. Altogether, this could be a more appropriate animal model to study the pathophysiology of diabetes and, eventually, related organ damage.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051549","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}
引用次数: 0
Protein intake counteracts alcohol intake in the regulation of postprandial FGF21 secretion in humans. 蛋白质摄入抵消酒精摄入对人类餐后FGF21分泌的调节。
IF 3.1 2区 医学
American journal of physiology. Endocrinology and metabolism Pub Date : 2025-09-10 DOI: 10.1152/ajpendo.00265.2025
Stina Ramne, Teresa Duarte da Costa Seco, Katharina B Kuentzel, Trisha J Grevengoed, Jasmin P Hjerresen, Thomas Moritz, Torben Hansen, Anne Raben, Niels Grarup
{"title":"Protein intake counteracts alcohol intake in the regulation of postprandial FGF21 secretion in humans.","authors":"Stina Ramne, Teresa Duarte da Costa Seco, Katharina B Kuentzel, Trisha J Grevengoed, Jasmin P Hjerresen, Thomas Moritz, Torben Hansen, Anne Raben, Niels Grarup","doi":"10.1152/ajpendo.00265.2025","DOIUrl":"https://doi.org/10.1152/ajpendo.00265.2025","url":null,"abstract":"<p><p>FGF21 is a hormone secreted from the liver in response to various nutritional stressors, suggested to be acting to balance dietary intake through negative feedback regulation. This meal study aimed to investigate two different potential nutrient interactions on postprandial FGF21 secretion in healthy human participants: 1) between intake of alcohol and protein and 2) between intake of alcohol and vitamin A (retinol). In a 4-arm, randomized, double-blinded, cross-over meal study (NCT06105476), postprandial circulating concentrations of FGF21, glucose, insulin, ethanol, and acetate were compared after intake of four different test drinks containing alcohol, alcohol+protein, alcohol+retinol or retinol in 27 healthy humans. The postprandial FGF21 response to the alcohol+protein drink was severely attenuated compared to the alcohol drink. The FGF21 response to the alcohol+retinol drink was similar to the alcohol drink, while there was no FGF21 response to the drink with retinol only. In conclusion, intake of protein inhibited the secretory FGF21 response to alcohol intake, while retinol intake did not appear to influence FGF21 secretion.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032697","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}
引用次数: 0
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