bims-obesme Biomed News
on Obesity metabolism
Issue of 2025–09–28
fourteen papers selected by
Xiong Weng, University of Edinburgh
  1. A consensus guide to preclinical indirect calorimetry experiments.
  2. Acetylation of the Mitochondrial Chaperone GRP75 Governs ER-Mitochondrial Calcium Homeostasis and Hepatocyte Insulin Resistance.
  3. Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α.
  4. Lysosomes signal through the epigenome to regulate longevity across generations.
  5. Ribonucleotide incorporation into mitochondrial DNA drives inflammation.
  6. BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity.
  7. A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics.
  8. Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits.
  9. Charcot-Marie-Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death.
  10. Mapping chromatin and DNA methylation landscapes at single-cell and single-molecule resolution.
  11. Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.
  12. Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.
  13. Nanomedicine targeting PPAR in adipose tissue macrophages improves lipid metabolism and obesity-induced metabolic dysfunction.
  14. WW Domain-Containing E3 Ubiquitin Protein Ligase 1 (WWP1) as a Factor in Obesity-Related Metabolic Disorders: Emerging Molecular Mechanisms in Metabolic Tissues.
  1. Nat Metab. 2025 Sep;7(9): 1765-1780
    A consensus guide to preclinical indirect calorimetry experiments.
    International Indirect Calorimetry Consensus Committee (IICCC)
      Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.
    DOI:  https://doi.org/10.1038/s42255-025-01360-4
  2. Adv Sci (Weinh). 2025 Sep 26. e08991
    Acetylation of the Mitochondrial Chaperone GRP75 Governs ER-Mitochondrial Calcium Homeostasis and Hepatocyte Insulin Resistance.
    Danni Wang, Jiaqi Zhang, Xinyu Yang, Qiqi Zhang, Xiuya Hu, Xin Lu, Hanni Li, Xue Bai, Kai Zhang, Michael N Sack, Yongsheng Chang, Yingmei Wang, Lingdi Wang, Lu Zhu.
      Overnutrition exacerbates insulin resistance (IR) and is linked to excessive mitochondrial protein acetylation. However, the molecular mechanism by which mitochondrial protein acetylation influences hepatic IR remains incompletely elucidated. To investigate this biology, GCN5L1 liver knockout mice (LKO), which exhibit blunted mitochondrial protein acetylation are utilized. Interestingly, the hepatocytes of LKO mice exhibit impaired insulin signaling and exaggerated endoplasmic reticulum (ER) stress. To explore putative mechanisms, protein-interaction and acetyl-proteome analyses are conducted following hepatic induction of GCN5L1. The mitochondrial chaperone GRP75 interacts with GCN5L1 and is acetylated on lysine residues K567 and K612 by GCN5L1 overexpression. Furthermore, GRP75-K567/612 acetylation reduces the assemble of IP3R1-GRP75-VDAC complex, which in turn leads to the maintenance of ER calcium homeostasis and insulin sensitivity. Interestingly, during high-fat diet feeding, mitochondria-localized GCN5L1 is significantly translocated to the cytosol. This translocation attenuates the acetylation of GRP75 at K567/612 and consequently enhances ER-mitochondrial calcium flux and induces ER stress. In parallel, deacetylation-mimicking mutated GRP75-K567/612 promotes IR in vivo. Consequently, these findings demonstrate that the acetylation-dependent modification of GRP75 plays a functional role in regulating overnutrition-induced IR.
    Keywords:  acetylation; insulin resistance; liver; metabolism; mitochondria
    DOI:  https://doi.org/10.1002/advs.202508991
  3. Nat Cardiovasc Res. 2025 Sep 24.
    Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α.
    Sumeet A Khetarpal, Haobo Li, Tevis Vitale, James Rhee, Saketh Challa, Claire Castro, Steffen Pabel, Yizhi Sun, Jing Liu, Dina Bogoslavski, Ariana Vargas-Castillo, Amanda L Smythers, Katherine A Blackmore, Louisa Grauvogel, Melanie J Mittenbühler, Melin J Khandekar, Casie Curtin, Jose Max Narvaez-Paliza, Chunyan Wang, Nicholas E Houstis, Hans-Georg Sprenger, Sean J Jurgens, Kiran J Biddinger, Alexandra Kuznetsov, Rebecca Freeman, Patrick T Ellinor, Matthias Nahrendorf, Joao A Paulo, Steven P Gygi, Phillip A Dumesic, Aarti Asnani, Krishna G Aragam, Pere Puigserver, Jason D Roh, Bruce M Spiegelman, Anthony Rosenzweig.
      Endurance exercise promotes adaptive growth and improved function of myocytes, which is supported by increased mitochondrial activity. In skeletal muscle, these benefits are in part transcriptionally coordinated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The importance of PGC-1α to exercise-induced adaptations in the heart has been unclear. Here we show that deleting PGC-1α specifically in cardiomyocytes prevents the expected benefits from exercise training and instead leads to heart failure after just 6 weeks of training. Consistent with this, in humans, rare genetic variants in PPARGC1A, which encodes PGC-1α, are associated with increased risk of heart failure. In this model, we identify growth differentiation factor 15 (GDF15) as a key heart-secreted mediator that contributes to this dysfunction. Blocking cardiac Gdf15 expression improves cardiac performance and exercise capacity in these mice. Finally, in human heart tissue, lower cardiomyocyte PPARGC1A expression is associated with higher GDF15 expression and reduced cardiomyocyte density. These findings uncover a crucial role for cardiomyocyte PGC-1α in enabling healthy cardiac adaptation to exercise in part through suppression of GDF15.
    DOI:  https://doi.org/10.1038/s44161-025-00712-3
  4. Science. 2025 Sep 25. 389(6767): 1353-1360
    Lysosomes signal through the epigenome to regulate longevity across generations.
    Qinghao Zhang, Weiwei Dang, Meng C Wang.
      The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic target of rapamycin (mTOR) signaling increased the expression of a histone H3.3 variant and increased its methylation on K79, leading to life-span extension across multiple generations. This transgenerational prolongevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase and was recapitulated by overexpressing H3.3 or the H3K79 methyltransferase. Thus, signals from a lysosome affect the epigenome and link the soma and germ line to mediate transgenerational inheritance of longevity.
    DOI:  https://doi.org/10.1126/science.adn8754
  5. Nature. 2025 Sep 24.
    Ribonucleotide incorporation into mitochondrial DNA drives inflammation.
    Amir Bahat, Dusanka Milenkovic, Eileen Cors, Mabel Barnett, Sadig Niftullayev, Athanasios Katsalifis, Marc Schwill, Petra Kirschner, Thomas MacVicar, Patrick Giavalisco, Louise Jenninger, Anders R Clausen, Vincent Paupe, Julien Prudent, Nils-Göran Larsson, Manuel Rogg, Christoph Schell, Isabella Muylaert, Erik Lekholm, Hendrik Nolte, Maria Falkenberg, Thomas Langer.
      Metabolic dysregulation can lead to inflammatory responses1,2. Imbalanced nucleotide synthesis triggers the release of mitochondrial DNA (mtDNA) to the cytosol and an innate immune response through cGAS-STING signalling3. However, how nucleotide deficiency drives mtDNA-dependent inflammation has not been elucidated. Here we show that nucleotide imbalance leads to an increased misincorporation of ribonucleotides into mtDNA during age-dependent renal inflammation in a mouse model lacking the mitochondrial exonuclease MGME14, in various tissues of aged mice and in cells lacking the mitochondrial i-AAA protease YME1L. Similarly, reduced deoxyribonucleotide synthesis increases the ribonucleotide content of mtDNA in cell-cycle-arrested senescent cells. This leads to mtDNA release into the cytosol, cGAS-STING activation and the mtDNA-dependent senescence-associated secretory phenotype (SASP), which can be suppressed by exogenously added deoxyribonucleosides. Our results highlight the sensitivity of mtDNA to aberrant ribonucleotide incorporation and show that imbalanced nucleotide metabolism leads to age- and mtDNA-dependent inflammatory responses and SASP in senescence.
    DOI:  https://doi.org/10.1038/s41586-025-09541-7
  6. Metabolism. 2025 Sep 20. pii: S0026-0495(25)00265-3. [Epub ahead of print] 156396
    BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity.
    Morgane A Philippe, Blandine Fruchet, Lucie Cagninacci, Lucie Beaudoin, Alexis Gadault, Bastien Aznar, Nicolas Venteclef, Etienne Challet, Agnès Lehuen, Ute C Rogner, Amine Toubal.
      Contemporary lifestyle modifications such as changes in nutritional and sleep/wake rhythms increase the risk of metabolic and inflammatory complications linked to obesity, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). BMAL2 (Brain and Muscle ARNT Like Protein 2) is a transcription factor belonging to the circadian clock transcriptional feedback loop which synchronizes internal biological rhythms to environment. In humans, reduced expression in white adipose tissue (WAT) and specific polymorphisms of BMAL2 are associated with obesity and T2D. In this study we report that Bmal2 deletion in mice leads to increased body weight gain during diet-induced obesity. Loss of BMAL2 triggers the inflammatory response by increasing Tnfα expression and modifying adipocyte progenitor fate. This results in reduced lipid storage capacity within the WAT and increased ectopic storage in the liver. These functional and structural alterations culminate in the onset of hepatic steatosis and insulin resistance in liver and WAT. Overall, our investigations underscore the role of BMAL2 in the development and function of adipocytes, as well as in their inflammatory potential within the WAT. Our findings contribute to the understanding of the role of circadian clock genes in obesity and interconnected metabolic complications.
    Keywords:  Adipose tissue; Circadian rhythm; Inflammation; Obesity; Preadipocytes
    DOI:  https://doi.org/10.1016/j.metabol.2025.156396
  7. Signal Transduct Target Ther. 2025 Sep 26. 10(1): 315
    A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics.
    Zhiheng Rao, Zhichao Chen, Yuxuan Bao, Zhenzhen Lu, Yuli Tang, Jiamei Zhu, Jianjia Ma, Siyang Dong, Jiawei Shi, Suhui Sheng, Yajing Chen, Jiaojiao Wang, Alan Vengai Mukondiwa, Ziyue Li, Xulan Wang, Zibo Huang, Chi Li, Wumengwei Ding, Mengjie Chen, Ziyi Han, Cong Wang, Xuebo Pan, Xiaojie Wang, Hong Zhu, Li Lin, Zhifeng Huang, Weiqin Lu, Xiaokun Li, Yongde Luo.
      The heart, an organ with a continuously high demand for energy, inherently lacks substantial reserves. The precise mechanisms that prioritize energy allocation to cardiac mitochondria, ensuring steady-state ATP production amidst high-energy organs, remain poorly understood. Our study sheds light on this process by identifying a two-strata flux system driven by the starvation hormone FGF21. We demonstrate that systemic disruptions in interorgan metabolite mobilization and transcardiac flux, arising from either adipose lipolysis or hepatic ketogenesis due to FGF21 deficiency, directly impair cardiac energetic performance. Locally, this impairment is linked to compromised intracardiac utilization of various metabolites via ketolysis and oxidation pathways, along with hindered mitochondrial biogenesis, TCA cycle, ETC flow, and OXPHOS. Consequently, the heart shifts to a hypometabolic, glycolytic, and hypoenergy state, with a reduced capacity to cope with physiological stressors such as fasting, starvation, strenuous exercise, endurance training, and cold exposure, leading to a diminished heart rate, contractility, and hemodynamic stability. Pharmacological or genetic restoration of FGF21 ameliorates these defects, reenergizing stress-exhausted hearts. This hierarchical energy-prioritizing mechanism is orchestrated by the LKB1-AMPK-mTOR energy stress response pathways. Disrupting cardiac LKB1 or mTOR pathways, akin to stalling mitochondrial energy conduits, obstructs the FGF21-governed cardiac energetic potential. Our findings reveal an essential two-strata energy flux system critical for cardiac energetic efficiency regulated by FGF21, which spatiotemporally optimizes interorgan and transcardiac metabolite flux and intracardiac mitochondrial energy sufficiency. This discovery informs the design of strategies for treating cardiac diseases linked to mitochondrial or energy deficiencies.
    DOI:  https://doi.org/10.1038/s41392-025-02402-9
  8. Am J Hum Genet. 2025 Sep 23. pii: S0002-9297(25)00359-3. [Epub ahead of print]
    Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits.
    Emma P Wilson, K Alaine Broadaway, Victoria A Parsons, Swarooparani Vadlamudi, Narisu Narisu, Sarah M Brotman, Kevin W Currin, Heather M Stringham, Michael R Erdos, Ryan Welch, Jeffrey K Holtzman, Timo A Lakka, Markku Laakso, Jaakko Tuomilehto, Michael Boehnke, Heikki A Koistinen, Francis S Collins, Stephen C J Parker, Laura J Scott, Karen L Mohlke.
      Identifying genetic variants that regulate gene expression can help uncover mechanisms underlying complex traits. We performed a meta-analysis of skeletal muscle expression quantitative trait locus (eQTL) using data from 1,002 individuals from two studies. A stepwise analysis identified 18,818 conditionally distinct signals for 12,283 genes, and 35% of these genes contained two or more signals. Colocalization of these eQTL signals with 26 muscular and cardiometabolic trait genome-wide association studies (GWASs) identified 2,252 GWAS-eQTL colocalizations that nominated 1,342 candidate genes. Notably, 22% of the GWAS-eQTL colocalizations involved non-primary eQTL signals. Additionally, 37% of the colocalized GWAS-eQTL signals corresponded to the closest protein-coding gene, while 44% were located >50 kb from the transcription start site of the nominated gene. To assess tissue specificity for a heterogeneous trait, we compared colocalizations with type 2 diabetes (T2D) signals across muscle, adipose, liver, and islet eQTLs; we identified 551 candidate genes for 309 T2D signals representing 36% of T2D signals tested and over 100 more than were detected with any one tissue alone. We then functionally validated the allelic regulatory effect of an eQTL variant for INHBB linked to T2D in both muscle and adipose tissue. Together, these results further demonstrate the value of skeletal muscle eQTLs in elucidating mechanisms underlying complex traits.
    Keywords:  GWAS; INHBB; allelic heterogeneity; colocalization; complex trait; eQTL; signal identification; skeletal muscle; transcriptomics; type 2 diabetes
    DOI:  https://doi.org/10.1016/j.ajhg.2025.09.003
  9. J Cell Sci. 2025 Sep 15. pii: jcs263691. [Epub ahead of print]138(18):
    Charcot-Marie-Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death.
    Mariana Joaquim, Maria-Bianca Bulimaga, Marie A Mohn, Solenn Plouzennec, Leon Osinski, Selver Altin, Esther Mahabir, Arnaud Chevrollier, Mafalda Escobar-Henriques.
      The neuropathy Charcot-Marie-Tooth (CMT) is an incurable disease with a lack of genotype-phenotype correlation. Variants of the mitochondrial protein mitofusin 2 (MFN2), a large GTPase that mediates mitochondrial fusion, are responsible for the subtype CMT type 2A (CMT2A). Interestingly, beyond membrane remodelling, additional roles of MFN2 have been identified, expanding the possibilities to explore its involvement in disease. Here, we investigated how cellular functions of MFN2 are associated with variants present in individuals with CMT2A. Using human cellular models, we observed that cells expressing CMT2A variants display increased endoplasmic reticulum (ER) stress and apoptotic cell death. Increased cleavage of PARP1, caspase 9, caspase 7 and caspase 3, alongside BAX translocation to mitochondria, pointed towards effects on intrinsic apoptosis. Moreover, although disruption of fusion and fission dynamics per se did not correlate with cell death markers, expression of MFN1 or MFN2 alleviated the apoptosis markers of CMT2A variant cell lines. In sum, our results highlight excessive cell death by intrinsic apoptosis as a potential target in CMT2A disease.
    Keywords:  Apoptosis; CMT2A; Cell death; Charcot–Marie–Tooth; Fusion; MFN2; Mitochondria
    DOI:  https://doi.org/10.1242/jcs.263691
  10. Nat Methods. 2025 Sep 26.
    Mapping chromatin and DNA methylation landscapes at single-cell and single-molecule resolution.
      
    DOI:  https://doi.org/10.1038/s41592-025-02848-3
  11. Elife. 2025 Sep 22. pii: RP96713. [Epub ahead of print]13
    Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.
    Gitanjali Roy, Rameesha Syed, Olivia Lazaro, Sylvia Robertson, Sean D McCabe, Daniela Rodriguez, Alex M Mawla, Travis S Johnson, Michael A Kalwat.
      Diabetes affects >10% of adults worldwide and is caused by impaired production or response to insulin, resulting in chronic hyperglycemia. Pancreatic islet β-cells are the sole source of endogenous insulin, and our understanding of β-cell dysfunction and death in type 2 diabetes (T2D) is incomplete. Single-cell RNA-seq data supports heterogeneity as an important factor in β-cell function and survival. However, it is difficult to identify which β-cell phenotypes are critical for T2D etiology and progression. Our goal was to prioritize specific disease-related β-cell subpopulations to better understand T2D pathogenesis and identify relevant genes for targeted therapeutics. To address this, we applied a deep transfer learning tool, DEGAS, which maps disease associations onto single-cell RNA-seq data from bulk expression data. Independent runs of DEGAS using T2D or obesity status identified distinct β-cell subpopulations. A singular cluster of T2D-associated β-cells was identified; however, β-cells with high obese-DEGAS scores contained two subpopulations derived largely from either non-diabetic (ND) or T2D donors. The obesity-associated ND cells were enriched for translation and unfolded protein response genes compared to T2D cells. We selected CDKN1C and DLK1 for validation by immunostaining in human pancreas sections from healthy and T2D donors. Both CDKN1C and DLK1 were heterogeneously expressed among β-cells. CDKN1C was increased in β-cells from T2D donors, in agreement with the DEGAS predictions, while DLK1 appeared depleted from T2D islets of some donors. In conclusion, DEGAS has the potential to advance our holistic understanding of the β-cell transcriptomic phenotypes, including features that distinguish β-cells in obese ND or lean T2D states. Future work will expand this approach to additional human islet omics datasets to reveal the complex multicellular interactions driving T2D.
    Keywords:  computational biology; human; machine learning; single cell; systems biology; transfer learning; type 2 diabetes; β-cell
    DOI:  https://doi.org/10.7554/eLife.96713
  12. Sci Adv. 2025 Sep 26. 11(39): eadt6366
    Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.
    Ashutosh Kumar, Yonghui Zhao, Litao Xie, Rahul Chadda, John D Tranter, Ryan T Mikami, Nihil Abraham, Juan Hong, Ethan Feng, David R Rawnsley, Haiyan Liu, Kayla M Henry, Gretchen Meyer, Meiqin Hu, Haoxing Xu, Antentor Hinton, Chad E Grueter, E Dale Abel, Andrew W Norris, Abhinav Diwan, Rajan Sah.
      The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A knockout cells. In vivo, LRRC8A-L706A;L707A knock-in mice exhibit increased adiposity, impaired glucose tolerance and insulin resistance associated with reduced skeletal muscle PI3K-AKT-mTOR signaling, glucose uptake, and impaired incorporation of glucose into glycogen. These data reveal a lysosomal LRRC8-mediated metabolic signaling function regulating lysosomal function, systemic glucose homeostasis, and insulin sensitivity.
    DOI:  https://doi.org/10.1126/sciadv.adt6366
  13. Sci Adv. 2025 Sep 26. 11(39): eads3731
    Nanomedicine targeting PPAR in adipose tissue macrophages improves lipid metabolism and obesity-induced metabolic dysfunction.
    Catherine C Applegate, Yifei Kang, Hongping Deng, Donglai Chen, Natalia Y Gonzalez Medina, Yuxiao Cui, Yujun Feng, Chia-Wei Kuo, Sayyed Hamed Shahoei, Hannah Kim, Hashni Epa Vidana Gamage, Matthew A Wallig, Erik R Nelson, Kelly S Swanson, Andrew M Smith.
      Excess body fat leads to an overabundance of adipose tissue macrophages (AT MΦs) with altered phenotypes that play pathogenic roles in obesity comorbidities including diabetes and cancer. Peroxisome proliferator-activated receptors (PPARs) are leading targets to modulate AT MΦ phenotype. Here, we developed a dextran-based nanomedicine that delivers PPARα/γ agonists to AT MΦs and improves obesity and diabetic phenotypes in vivo. Within 1 week of treatment, AT MΦs decreased and became lipid laden, while extracellular vesicles secreted from AT decreased and reduced in lipid content. Within 2 weeks, glucose tolerance returned to levels of lean controls, followed by weight loss and reduced food intake. After 4 weeks, AT browning and amelioration of hepatic steatosis were evident. The physiological shifts were reproducible in three rodent models of obesity, spanning sexes and gonadal status. Effects were enhanced for the targeted nanomedicine compared with free drugs at equivalent doses, supporting the hypothesis that targeted PPAR activation in AT MΦs benefits systemic metabolism.
    DOI:  https://doi.org/10.1126/sciadv.ads3731
  14. Int J Mol Sci. 2025 Sep 19. pii: 9172. [Epub ahead of print]26(18):
    WW Domain-Containing E3 Ubiquitin Protein Ligase 1 (WWP1) as a Factor in Obesity-Related Metabolic Disorders: Emerging Molecular Mechanisms in Metabolic Tissues.
    Yuka Nozaki, Yuhei Mizunoe, Masaki Kobayashi, Yoshikazu Higami.
      WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a member of the homologous to E6AP C-terminus-type E3 ubiquitin protein ligase family. Although WWP1 plays a role in several human diseases, including infectious diseases, neurological disorders, and cancers, there is emerging evidence that WWP1 is also associated with metabolic disorders. In this review, we discuss the regulation and molecular function of WWP1 and its contribution to obesity-related metabolic disorders, particularly in white adipose tissue and the liver. We highlight the need for further research to deepen our understanding of how WWP1 may be implicated in metabolic dysfunction and facilitate the development of novel therapeutic strategies that target WWP1.
    Keywords:  WWP1; hepatic steatosis; insulin signaling; lipolysis; obesity; oxidative stress; white adipose tissue
    DOI:  https://doi.org/10.3390/ijms26189172
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