Journal of physiology and biochemistry最新文献

GSDMD palmitoylation induces acinar cell pyroptosis via promoting GSDMD-N oligomerization to aggravate hyperlipidemic acute pancreatitis.

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-20 DOI: 10.1007/s13105-026-01247-2

Hongwei Xu, Chunlin Liu, Dajun Wang, Lu Zhang, Yanan Peng, Liang Wang

{"title":"GSDMD palmitoylation induces acinar cell pyroptosis via promoting GSDMD-N oligomerization to aggravate hyperlipidemic acute pancreatitis.","authors":"Hongwei Xu, Chunlin Liu, Dajun Wang, Lu Zhang, Yanan Peng, Liang Wang","doi":"10.1007/s13105-026-01247-2","DOIUrl":"https://doi.org/10.1007/s13105-026-01247-2","url":null,"abstract":"Pancreatic acinar cell pyroptosis played a key role in acute pancreatitis (AP), while the underlying molecular mechanisms were unclear. In this study, hyperlipidemic acute pancreatitis (HLAP) model mice and primary acinar cells were employed for the in vivo and in vitro experiments, respectively. Western blot was employed to assess Gasdermin D-N-terminal pore-forming domain (GSDMD-N) oligomerization; Flow cytometry was employed to assess cell pyroptosis; Immunofluorescence was performed to assess GSDMD-N location in the cytoplasm; HE and TUNEL staining were employed to assess the pathological changes and cell apoptosis of pancreatic tissues. Palmitic acid levels were elevated in serum and pancreatic tissues of HLAP mice, palmitoyltransferase Zinc Finger DHHC Domain-Containing Protein 13 (ZDHHC13) and ZDHHC15 expression levels were markedly increased in primary acinar cells of HLAP mice. Acinar cells of HLAP mice exhibited the increased pyroptosis, which was evidenced by the increased cleaved-caspase-1 and GSDMD-N protein levels, Interleukin (IL)-1β, IL-18, and lactate dehydrogenase (LDH) release, GSDMD-N oligomerization, and caspase-1+PI+ cells. Mechanistically, palmitic acid induced GSDMD palmitoylation. ZDHHC15 interacted with GSDMD, and ZDHHC15 knockdown reduced GSDMD-N oligomerization and thereby suppressed pyroptosis in palmitic acid-treated acinar cells. The in vivo experiments further revealed that AAV-sh-ZDHHC15 reduced cell apoptosis and GSDMD-N oligomerization in pancreatic tissues of HLAP mice. In conclusion, this study identified a potential regulatory pathway of HLAP involving ZDHHC15-dependent modulation of GSDMD palmitoylation and subsequent GSDMD-N oligomerization.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Irisin promotes lipid clearance through the CD81-integrin-FAK axis in steatotic hepatocytes. 鸢尾素通过cd81 -整合素- fak轴促进脂肪变性肝细胞的脂质清除。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-17 DOI: 10.1007/s13105-026-01245-4

Po-Han Chen, Yu-Chun Lin, Jian-Han Chen, Po-Huang Lee, Yo-Chen Chang, Cheuk-Kwan Sun, Ying-Hsien Kao, Ming-Hong Tai

{"title":"Irisin promotes lipid clearance through the CD81-integrin-FAK axis in steatotic hepatocytes.","authors":"Po-Han Chen, Yu-Chun Lin, Jian-Han Chen, Po-Huang Lee, Yo-Chen Chang, Cheuk-Kwan Sun, Ying-Hsien Kao, Ming-Hong Tai","doi":"10.1007/s13105-026-01245-4","DOIUrl":"https://doi.org/10.1007/s13105-026-01245-4","url":null,"abstract":"Irisin, an exercise-induced myokine, regulates metabolic homeostasis, but its receptor mechanisms in metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. This study investigates the role of the co-receptor CD81 in modulating irisin signaling and intrahepatic lipid homeostasis. Clinical correlations were analyzed in 88 bariatric surgery patients and liver biopsy cohorts (n = 62). In vitro steatosis models included Clone-9 rat hepatocytes, primary mouse hepatocytes, and human HepG2 and Huh-7 cells treated with fatty acids and recombinant irisin. Receptor interactions and downstream signaling were evaluated using co-immunoprecipitation, RT-qPCR, Western blotting, subcellular fractionation, and lipid staining. Serum irisin positively correlated with BMI and steatosis grade, but inversely associated with triglycerides, fasting glucose, and HbA1c. Intrahepatic FNDC5/irisin and integrin β5 correlated with serum triglycerides, whereas membranous CD81 expression declined with advancing steatosis. Free fatty acids induced FNDC5/irisin and perilipins (Plin2/Plin5) while downregulating CD81. Co-immunoprecipitation confirmed physical interaction between CD81 and integrins αV/β5 subunits. CD81 overexpression enhanced irisin-induced focal adhesion kinase (FAK) phosphorylation, restricted PPARγ nuclear translocation, suppressed Plin2/Plin5 expression, and attenuated lipid accumulation. Conversely, FAK inhibition using BI 853520 or CD81 knockdown abrogated these protective anti-steatotic effects. In conclusion, CD81 serves as a functional co-receptor that physically associates with the integrin αV/β5 complex to amplify irisin-FAK signaling, restrict PPARγ nuclear transactivation, and suppress lipid droplet accumulation in cultured hepatocytes in vitro. These findings highlight the CD81-integrin-FAK axis as a potential candidate for further translational exploration in MASLD.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The multifaceted role of 3-methyladenine in cancer therapy. 3-甲基腺嘌呤在癌症治疗中的多方面作用。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-15 DOI: 10.1007/s13105-026-01239-2

Umm E Laila, Bo Wang, Maryam Mumtaz, Komal Gulshad, Malaika Niaz, Muhammad Maaz Qureshi, Meng-Yuan Hao, Umme Ammara Sial, Dong-Dong Wu

{"title":"The multifaceted role of 3-methyladenine in cancer therapy.","authors":"Umm E Laila, Bo Wang, Maryam Mumtaz, Komal Gulshad, Malaika Niaz, Muhammad Maaz Qureshi, Meng-Yuan Hao, Umme Ammara Sial, Dong-Dong Wu","doi":"10.1007/s13105-026-01239-2","DOIUrl":"https://doi.org/10.1007/s13105-026-01239-2","url":null,"abstract":"3-Methyladenine (3-MA), an early autophagy inhibitor, blocks autophagosome formation mainly by inhibiting class III phosphatidylinositol 3-kinase (PI3K) vacuolar protein sorting 34, while its concurrent inhibition of class I PI3K can produce opposing effects on autophagic flux depending on nutrient status. This Review examines the context-dependent roles of 3-MA across cancer types. When autophagy serves a pro-survival function, 3-MA-mediated inhibition tends to attenuate this protective response, thereby potentiating the cytotoxicity of chemotherapeutics, targeted drugs, and natural compounds, and helping to overcome acquired resistance. However, in some settings-such as colorectal cancer without therapeutic pressure-autophagy suppression may instead promote epithelial-mesenchymal transition and metastasis. The pharmacokinetic shortcomings and off-target effects of 3-MA have motivated the design of nanocarriers for tumor-specific co-delivery, aiming to improve bioavailability and avoid paradoxical autophagy induction. Ultimately, the lasting contribution of 3-MA may be its utility as a mechanistic probe that uncovers key autophagy regulatory nodes, paving the way for next-generation selective modulators and biomarker-driven strategies.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global deletion of the triglyceride-synthesizing enzyme TMEM68 disrupts hepatic lipid homeostasis in mice. 甘油三酯合成酶TMEM68的整体缺失破坏了小鼠肝脂质稳态。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-09 DOI: 10.1007/s13105-026-01244-5

Haonan Wang, Huimin Pang, Christoph Heier, Chunyan Zhang, Tingting Li, Yuhang Liu, Feifei Huang, Pingan Chang

{"title":"Global deletion of the triglyceride-synthesizing enzyme TMEM68 disrupts hepatic lipid homeostasis in mice.","authors":"Haonan Wang, Huimin Pang, Christoph Heier, Chunyan Zhang, Tingting Li, Yuhang Liu, Feifei Huang, Pingan Chang","doi":"10.1007/s13105-026-01244-5","DOIUrl":"10.1007/s13105-026-01244-5","url":null,"abstract":"Transmembrane protein 68 (TMEM68) mediates triacylglycerol (TAG) synthesis in mammals independently of canonical diacylglycerol acyltransferase (DGAT) 1 and DGAT2 enzymes. However, the in vivo roles of TMEM68 including its contribution to tissue-specific TAG formation remain largely elusive. In this study, we used a global Tmem68 knockout mouse model to investigate the impact of TMEM68 deficiency on lipid and energy metabolism of the liver. We found that loss of TMEM68 leads to a transient reduction in hepatic TAG storage and circulating ketone bodies approximately 4 weeks after birth. TMEM68-deficient livers exhibited reduced abundance of distinct acylglycerols and fatty acids, altered glycerophospholipid composition, and accumulation of polar ether lipids. Primary TMEM68-deficient hepatocytes also had reduced TAG and lipid droplet contents. RNA sequencing revealed that genes involved in multiple fatty acid metabolic processes and ketogenesis were repressed in Tmem68 knockout livers. Furthermore, Tmem68 ablation reduced hepatic cholesterol esters and modulated bile acid composition. In summary, our study identifies TMEM68 as a positive regulator of hepatic storage lipid levels and demonstrates a multifaceted embedding of the enzyme in hepatic lipid and energy metabolic pathways.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of adipocyte-macrophage interaction via CSF1-CSF1R by curcumin. 姜黄素通过CSF1-CSF1R抑制脂肪细胞-巨噬细胞相互作用。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-08 DOI: 10.1007/s13105-026-01240-9

Youngjoo Kwon, Chanme Son, Minjung Han

{"title":"Inhibition of adipocyte-macrophage interaction via CSF1-CSF1R by curcumin.","authors":"Youngjoo Kwon, Chanme Son, Minjung Han","doi":"10.1007/s13105-026-01240-9","DOIUrl":"10.1007/s13105-026-01240-9","url":null,"abstract":"Adipocytes (Ad), macrophages (Mac), and lipopolysaccharide (LPS) in the adipose tissue (AT) of individuals with obesity may jointly contribute to obesity-induced pathogenesis. This study aims to examine the roles of adipocyte-macrophage interaction (AMI) and LPS in obesity-induced pathogenesis, as well as the effects of curcumin (Cur) on these interactions. An indirect co-culture model using conditioned media (CM) from 3T3-L1 Ad and J774A.1 Mac, with LPS, was used. AMI in AT and its association with systemic insulin resistance (IR) were further evaluated in a high-fat diet (HFD)-induced obese mouse model. Colony-stimulating factor 1 (CSF1), produced by Ad and Mac, additively enhanced LPS-induced Mac chemotaxis. Compared with LPS, CM from Mac and Ad differentially influenced inflammatory cytokine secretion by the other cell type, with some cytokines markedly increased by CM prepared with LPS. Furthermore, in Ad, LPS and Mac-derived CM reduced glucose transporter 4 (GLUT4) expression, with a greater reduction observed when combined. Cur inhibited some AMI-induced inflammation but did not restore AMI-repressed GLUT4 expression. Cur specifically suppressed CSF1 secretion in both cell types and inhibited colony-stimulating factor receptor (CSF1R) activation in Mac, thereby preventing AMI. AT from HFD-induced obese mice exhibited increased CSF1R and signal transducer and activator of transcription 3 activation but reduced perilipin 1 expression at AMI sites. These obese mice also showed IR and elevated inflammatory cytokine expression in AT, which Cur attenuated regardless of whether it was administered before or after obesity induction. Cur may inhibit obesity-induced inflammation and IR by preventing AMI.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging mechanisms of ATG8-independent non-canonical autophagy. 不依赖atg8的非典型自噬的新机制。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-07 DOI: 10.1007/s13105-026-01243-6

Suvam Saha, Debasish Kumar Ghosh

{"title":"Emerging mechanisms of ATG8-independent non-canonical autophagy.","authors":"Suvam Saha, Debasish Kumar Ghosh","doi":"10.1007/s13105-026-01243-6","DOIUrl":"10.1007/s13105-026-01243-6","url":null,"abstract":"ATG8-independent autophagy represents an emerging field of cellular degradation that challenges the long-held view that LC3/GABARAP lipidation is universally required for autophagosome formation and autophagic flux. Over the past decade, studies across mammals, plants, and protozoa have revealed that cells can execute degradative mechanisms through alternative macroautophagy, microautophagy-like pathways, and autophagy-like systems that operate with reduced or absent reliance on ATG8 proteins. These discoveries have reshaped the conceptual framework of autophagy by separating membrane biogenesis, cargo sequestration, and lysosomal delivery into potentially ATG8-uncoupled modules. ATG8-independent pathways are now recognized as important for stress adaptation, organelle quality control, developmental remodeling, and selective cargo degradation. This review summarizes the historical development, mechanistic diversity, and biological relevance of ATG8-independent autophagy, and discusses its implications for disease biology and therapeutic targeting. Understanding these unconventional pathways will be essential for a complete view of autophagic regulation in health and disease.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis. 综合代谢组学和丙二酰蛋白质组学揭示了肝脏纤维化中代谢重编程和赖氨酸丙二酰化之间的串扰。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-07 DOI: 10.1007/s13105-026-01241-8

Yun Wang, Huiran Zheng, Ran Chen, Yihang Song, Dongdong Song, Ranran Sun, Zujiang Yu, Liwen Liu

{"title":"Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis.","authors":"Yun Wang, Huiran Zheng, Ran Chen, Yihang Song, Dongdong Song, Ranran Sun, Zujiang Yu, Liwen Liu","doi":"10.1007/s13105-026-01241-8","DOIUrl":"10.1007/s13105-026-01241-8","url":null,"abstract":"Lysine malonylation (Kmal), a recently identified post-translational modification (PTM) of proteins, has been linked to energy metabolism and implicated in various pathological disorders, including liver diseases. However, the specific roles of Kmal in hepatic fibrosis remain enigmatic. This study aims to investigate novel post-translational modifications and the underlying mechanisms involved in liver fibrosis. Utilizing untargeted metabolomics on carbon tetrachloride (CCl4)-induced mouse fibrotic liver tissues, we observed significant metabolic dysregulation during the liver fibrotic process, characterized by notably increased levels of malonyl coenzyme A (CoA). Additionally, the fibrotic liver tissues exhibited dramatically elevated Kmal levels and a high abundance of acetyl-CoA carboxylase 1 (ACC1), an enzyme essential for converting acetyl-CoA to malonyl-CoA, compared to normal liver tissues. Furthermore, 4D label-free malonylation quantitative proteomics was employed to characterize the malonyl proteome in fibrotic liver tissues. A total of 3,512 malonylated sites in proteins were identified, revealing significant enrichment in metabolism-related pathways, such as the urea cycle, TCA cycle, and fatty acid biosynthesis and oxidation. And both the protein expression status and Kmal level of ACSL4 was significantly upregulated in fibrotic liver tissues. Collectively, these results illuminate a potential regulatory mechanism of energy metabolism and underscore the significance of Kmal for future therapeutic development in liver fibrosis.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Relationship between muscle FNDC5, FGF21 mRNA, miR-150 and bone loss after sciatic denervation. 修正：坐骨神经去神经后肌肉FNDC5、FGF21 mRNA、miR-150与骨丢失的关系。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-05 DOI: 10.1007/s13105-026-01242-7

Teresa Priego, Elena Nebot-Valenzuela, Álvaro Moreno-Rupérez, Miriam Granado, Daniel Jaque, Peter Pietschmann, Ana Isabel Martín, Asunción López-Calderón

引用次数: 0

Programmed cell death protein 4 (PDCD4): a pleiotropic regulator in cardiovascular diseases. 程序性细胞死亡蛋白4 (PDCD4)：心血管疾病的多效调节因子。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-03 DOI: 10.1007/s13105-026-01237-4

Mingbo Zheng, Xiaoying Jiang

{"title":"Programmed cell death protein 4 (PDCD4): a pleiotropic regulator in cardiovascular diseases.","authors":"Mingbo Zheng, Xiaoying Jiang","doi":"10.1007/s13105-026-01237-4","DOIUrl":"10.1007/s13105-026-01237-4","url":null,"abstract":"Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, yet the molecular mechanisms are incompletely understood. Programmed cell death protein 4 (PDCD4), originally identified as a tumor suppressor and inhibitor of eIF4A-dependent translation, has emerged as a cardiovascular stress-response node. Accumulating evidence indicates that PDCD4 expression is controlled at epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels. Across atherosclerosis, myocardial infarction, myocardial ischemia/reperfusion injury, cardiomyopathy, atrial fibrillation, pulmonary hypertension, and aneurysm, dysregulated PDCD4 links noncoding-RNA signaling and translational control to inflammation, apoptosis, autophagy, oxidative and mitochondrial injury, and phenotypic remodeling. Most experimental studies associate PDCD4 suppression with cardiovascular protection. However, the biological effects of PDCD4 appear to vary according to cell lineage, disease stage, subcellular localization, post-translational state, and tissue microenvironment. This review summarizes the molecular architecture and regulatory networks of PDCD4, integrates disease-specific evidence and cardiovascular functions, and critically discusses the opportunities and challenges of targeting PDCD4 for cardiovascular therapy.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myokines and mitochondrial function in cardiometabolic diseases. 心肌代谢疾病中的肌因子和线粒体功能。

IF 5.1 3区生物学

Journal of physiology and biochemistry Pub Date : 2026-10-02 DOI: 10.1007/s13105-026-01233-8

Jairo E Saavedra, Jaime Gallo-Villegas, Juan C Calderón

{"title":"Myokines and mitochondrial function in cardiometabolic diseases.","authors":"Jairo E Saavedra, Jaime Gallo-Villegas, Juan C Calderón","doi":"10.1007/s13105-026-01233-8","DOIUrl":"10.1007/s13105-026-01233-8","url":null,"abstract":"Cardiometabolic diseases (CMD) encompass a group of disorders sharing a common pathophysiology that increases the risk of cardiovascular disease and mortality. Key events underlying CMD pathophysiology include insulin resistance, low-grade inflammation, altered hormonal and myokine profiles, and mitochondrial dysfunction. The latter manifests as reduced mitochondrial mass and oxidative function, increased oxidative stress, altered Ca2+ handling and decreased mitochondrial membrane potential. Skeletal muscle plays a pivotal role in CMD pathophysiology through two main mechanisms: i) the storage and oxidation of energy substrates and ii) the release of myokines, which in turn modulate metabolism and mitochondrial function. Here, we propose that the unfavorable myokine profile associated with CMD pathophysiology leads to mitochondrial alterations, and that restoring a healthy myokine profile helps improve mitochondrial structure, function, and overall metabolic health. To test this idea, in this narrative review, we critically present evidence of an altered myokine profile in CMD and highlight the most important mitochondrial alterations in CMD before examining the direct effect of specific myokines on mitochondria and CMD-associated mitochondrial dysfunction. Finally, we summarize the effects of therapeutic interventions on both the myokine profile and mitochondrial function, also appraising human trials that use myokine-based interventions to improve CMD. We focus on molecular mechanisms and causal relationships, while also indicating novel perspectives in the field. Understanding the role of mitochondria in the effect of myokines on metabolic health may open new preventive and therapeutic strategies for addressing CMD more efficiently.","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"82 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0