Molecular and Cellular Endocrinology最新文献

{"title":"Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice","authors":"Jie Lin ,&nbsp;Yikai Shen ,&nbsp;Yiwen Xia ,&nbsp;Ying Li ,&nbsp;Tianlu Jiang ,&nbsp;Xusheng Shen ,&nbsp;Yiwang Fu ,&nbsp;Diancai Zhang ,&nbsp;Li Yang ,&nbsp;Hao Xu ,&nbsp;Zekuan Xu ,&nbsp;Linjun Wang","doi":"10.1016/j.mce.2025.112464","DOIUrl":"10.1016/j.mce.2025.112464","url":null,"abstract":"<div><h3>Objective</h3><div>The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.</div></div><div><h3>Methods</h3><div>We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (<em>GCG</em>), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.</div></div><div><h3>Conclusions</h3><div>ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112464"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029201","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}

{"title":"Loss of chemerin prevents ovariectomy-induced osteoporosis in mice through intraosseous vascular remodeling","authors":"Bingjie Wang ,&nbsp;Jinghuai Ni ,&nbsp;Lingling Yu ,&nbsp;Shuai Chen ,&nbsp;Wenbin Shang ,&nbsp;Penghua Fang ,&nbsp;Wen Min","doi":"10.1016/j.mce.2025.112465","DOIUrl":"10.1016/j.mce.2025.112465","url":null,"abstract":"<div><div>Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2^−/−) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2^−/− mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2^−/− mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2^−/− mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112465"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029193","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}

{"title":"Skeletal muscle disorders as risk factors for type 2 diabetes","authors":"Eshwar R. Tammineni ,&nbsp;Carlo Manno ,&nbsp;Goldie Oza ,&nbsp;Lourdes Figueroa","doi":"10.1016/j.mce.2025.112466","DOIUrl":"10.1016/j.mce.2025.112466","url":null,"abstract":"<div><div>The incidence and prevalence of muscular disorders and of type 2 diabetes (T2D) is increasing and both represent highly significant healthcare problems, both economically and compromising quality of life. Interestingly, skeletal muscle dysfunction and T2D share some commonalities including dysregulated glucose homeostasis, increased oxidative stress, dyslipidemia, and cytokine alterations. Several lines of evidence have hinted to a relationship between skeletal muscle dysfunction and T2D. For instance, T2D affects skeletal muscle morphology, functionality, and overall health through altered protein metabolism, impaired mitochondrial function, and ultimately cell viability. Conversely, humans suffering from myopathies and their experimental models demonstrated increased incidence of T2D through altered muscle glucose disposal function due to abnormal calcium homeostasis, compromised mitochondrial function, dyslipidemia, increased inflammatory cytokines and fiber size alterations and disproportions. Lifestyle modifications are essential for improving and maintaining mobility and metabolic health in individuals suffering from myopathies along with T2D. In this review, we updated current literature evidence on clinical incidence of T2D in inflammatory, mitochondrial, metabolic myopathies, and muscular dystrophies and further discussed the molecular basis of these skeletal muscle disorders leading to T2D.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112466"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029200","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}

{"title":"Identification of puberty related miRNAs in the hypothalamus of female mice","authors":"Pavlos Fanis ,&nbsp;Maria Morrou ,&nbsp;Marios Tomazou ,&nbsp;Hend Abdulgadr M. Alghol ,&nbsp;George M. Spyrou ,&nbsp;Vassos Neocleous ,&nbsp;Leonidas A. Phylactou","doi":"10.1016/j.mce.2025.112468","DOIUrl":"10.1016/j.mce.2025.112468","url":null,"abstract":"<div><h3>Background and aims</h3><div>Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty.</div></div><div><h3>Methods</h3><div>Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis.</div></div><div><h3>Results</h3><div>Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation.</div></div><div><h3>Conclusion</h3><div>The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"Article 112468"},"PeriodicalIF":3.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024109","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}

{"title":"The impact of obesity on mitochondrial dysfunction during pregnancy","authors":"Mariana Pacheco de Oliveira,&nbsp;Larissa Espindola da Silva,&nbsp;Bruna Barros Fernandes,&nbsp;Mariella Reinol Steiner,&nbsp;Debora Gehrke Pistóia,&nbsp;Tamires dos Santos Cichella,&nbsp;Luana Bahia Jacinto,&nbsp;Karoline Marcondes Spuldaro,&nbsp;Betine Pinto Moehlecke Iser,&nbsp;Gislaine Tezza Rezin","doi":"10.1016/j.mce.2025.112463","DOIUrl":"10.1016/j.mce.2025.112463","url":null,"abstract":"<div><div>Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"Article 112463"},"PeriodicalIF":3.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008530","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}

{"title":"GSTA2 overexpression alleviates bis (2-ethylhexyl) phthalate (DEHP)-induced male reproductive disorders by inhibiting oxidative stress-mediated cell apoptosis via the activated PI3K/AKT signaling pathway","authors":"Lei Wei ,&nbsp;Zonggang Feng ,&nbsp;Qian Dou ,&nbsp;Genhong Mao ,&nbsp;Hu Zhao ,&nbsp;Xinghua Zhao ,&nbsp;Bin Hao","doi":"10.1016/j.mce.2025.112462","DOIUrl":"10.1016/j.mce.2025.112462","url":null,"abstract":"<div><div>Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10⁷ TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders <em>in vitro</em>. Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis <em>via</em> the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112462"},"PeriodicalIF":3.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008522","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}

{"title":"GDF15 inhibits early-stage adipocyte differentiation by enhancing HOP2 expression and suppressing C/EBPα expression","authors":"Haeng Jun Kim ,&nbsp;Sung-Un Kang ,&nbsp;Hyo Jeong Kim ,&nbsp;Yun Sang Lee ,&nbsp;Chul-Ho Kim","doi":"10.1016/j.mce.2025.112461","DOIUrl":"10.1016/j.mce.2025.112461","url":null,"abstract":"<div><div>Excessive adipocyte differentiation and accumulation contribute to the development of metabolic disorders. Growth differentiation factor 15 (GDF15) plays an essential role in energy homeostasis and is considered an anti-obesity factor; however, elevated serum levels of endogenous GDF15 have been reported in certain individuals with obesity. In this study, to gain a better understanding of this complex relationship between GDF15 levels and obesity, we investigated GDF15 expression and function during adipogenesis. Compared with mice fed a normal diet, those fed a short-term high-fat diet exhibited a reduction in epididymal white adipose tissue and serum GDF15 expression. These results were confirmed in human adipose-derived stem cells that showed reduced GDF15 expression during adipogenesis differentiation. During adipogenesis, GDF15 was primarily degraded via the autophagy lysosomal pathway, and GDF15 overexpression in pre-adipocytes inhibited adipogenesis by suppressing CCAAT enhancer binding protein alpha (<em>C/EBPα</em>). Furthermore, whereas we detected a reduction in homologous-pairing protein 2 (HOP2) expression during adipogenesis, expression increased in response to an overexpression of GDF15. Furthermore, following knockdown of HOP2 during GDF15 overexpression, there was no suppression of C/EBPα expression. These findings indicate that GDF15 undergoes lysosomal degradation via an autophagic pathway and suppresses adipocyte differentiation via the HOP2-mediated inhibition of C/EBPα expression. Collectively, our findings indicate that GDF15 could serve as a potential therapeutic target for the treatment of metabolic disorders.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"Article 112461"},"PeriodicalIF":3.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008535","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}

{"title":"Transcriptomic analysis of effects of developmental PCB exposure in the hypothalamus of female rats","authors":"Madeline Streifer ,&nbsp;Emily N. Hilz ,&nbsp;Raj Raval ,&nbsp;Dennis C. Wylie ,&nbsp;Andrea C. Gore","doi":"10.1016/j.mce.2025.112460","DOIUrl":"10.1016/j.mce.2025.112460","url":null,"abstract":"<div><div>This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8–18 and after birth from postnatal (P) days 1–21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these latter phenotypes. We used 3’ targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112460"},"PeriodicalIF":3.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971622","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}

{"title":"EDNRB negatively regulates glycolysis to exhibit anti-tumor functions in prostate cancer by cGMP/PKG pathway","authors":"Xun Li,&nbsp;Bide Liu,&nbsp;Shuheng Wang,&nbsp;Qiang Dong,&nbsp;Jiuzhi Li","doi":"10.1016/j.mce.2025.112459","DOIUrl":"10.1016/j.mce.2025.112459","url":null,"abstract":"<div><div>Prostate cancer (PCa) is the most prevalent cancer in men and the leading cause of cancer-related mortality. Recent studies have highlighted the pivotal role of glycolysis in tumor progression. This study aimed to investigate the involvement of the EDNRB gene and its ligand endothelin 3 (EDN3) in glycolysis in PCa and to elucidate its underlying molecular mechanism. Quantitative reverse transcription PCR (RT-qPCR) and methylation-specific PCR (MSP) were used to probe EDNRB expression and methylation in PCa tissues. Cell proliferation and glycolysis in PCa cells were evaluated using Cell Counting Kit-8 (CCK-8), EDU staining, Seahorse assay, and biochemical kits to analyze the effects of EDN3/EDNRB. The underlying molecular mechanism was further explored through Western blotting. The <em>in vivo</em> effect of EDNRB on tumor growth was examined using a xenograft tumor model. Our findings revealed that EDNRB was hypermethylated and downregulated in PCa tissues and cell lines. Overexpression of EDNRB or EDN3 led to reduced cell proliferation and downregulation of glycolytic markers. EDNRB also decreased the extracellular acidification rate (ECAR) baseline and increased the oxygen consumption rate (OCR) baseline, indicating a shift away from glycolysis. Additionally, the anticancer effects of EDNRB or EDN3 was reversed upon inhibition of the cGMP/PKG pathway. <em>In vivo,</em> enhanced EDNRB expression significantly suppressed tumor growth. Therefore, EDNRB or EDN3 possess anticancer potential in PCa, primarily through the regulation of glycolysis via the cGMP/PKG pathway.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"Article 112459"},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951784","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}

{"title":"Housing temperature influences metabolic phenotype of heart failure with preserved ejection fraction in J vs N strain C57BL/6 mice","authors":"Rajesh Chaudhary ,&nbsp;Tahra K. Suhan ,&nbsp;Chao Wu ,&nbsp;Afnan Alzamrooni ,&nbsp;Nageswara Madamanchi ,&nbsp;Ahmed Abdel-Latif","doi":"10.1016/j.mce.2025.112457","DOIUrl":"10.1016/j.mce.2025.112457","url":null,"abstract":"<div><div>Preclinical heart failure studies rely heavily on mouse models despite their higher metabolic and heart rates compared to humans. This study examines how mouse strain (C57BL/6J vs. C57BL/6N) and housing temperature (23 °C vs. 30 °C) affect a well-established two-hit HFpEF model using high-fat diet with L-NAME treatment in male C57BL/6 mouse. Metabolic parameters and cardiac function were assessed at baseline, week 5, and week 15. Thermoneutral housing (30 °C) reduced early diastolic dysfunction in the J strain and altered metabolic profiles in both strains, decreasing energy expenditure and fat oxidation. The J strain specifically showed reduced respiratory exchange ratio and glucose oxidation at 30 °C. While physical activity remained constant across groups, both strains exhibited increased cardiac fibrosis and inflammatory gene expression under HFD + L-NAME, independent of housing temperature. These findings reveal strain-specific physiological adaptations to housing temperature, emphasizing the need to consider environmental conditions in heart failure research carefully.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"Article 112457"},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951786","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}