bims-mimead 2026-11-08 papers

bims-mimead

Biomed News

on Adipose tissue and metabolic disease

Issue of 2026–11–08
eleven papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht

Inflammatory signature of subcutaneous fat after weight loss and regain in women undergoing repeated bariatric surgery.
Acute sprint exercise transcriptome in adipose tissue of healthy adults: Associations with growth hormone.
Circulating Plasma Adiposomes as a Partial Lipidomic Readout of Matched Subcutaneous Adipose Tissue: Implications for Interorgan Communication.
Differentiated obesity treatment: Pharmacological CRF2 agonism drives fat loss, skeletal muscle hypertrophy and improved glucose metabolism in preclinical obesity.
Comparative and Sex-Specific Assessment of Proteomics, Clinical, and Genomic Data on Visceral Adipose Tissue Volume Using Machine Learning in UK Biobank: Advancing Precision Medicine.
Short-Term Unacylated Ghrelin Administration Improves Pyruvate Tolerance Without Chronically Altering Skeletal Muscle, Liver, or Adipose Tissue Insulin Response in Healthy Rats.
Fine mapping of early adipogenesis identifies committed progenitors with dual white and beige potential.
MKP-2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice.
Tissue-Specific Regulation of Glucose and Lipid Metabolism by miR-29a in Insulin Resistance and Type 2 Diabetes.
Multi-target phosphodiesterase inhibition overcomes adipose catecholamine resistance and ameliorates systemic lipotoxicity.
A transcriptional and cellular exploration of obesity and type II diabetes in human adipose tissues.

J Clin Endocrinol Metab. 2026 Nov 03. pii: dgag447. [Epub ahead of print]

Inflammatory signature of subcutaneous fat after weight loss and regain in women undergoing repeated bariatric surgery.

Ariel Shneyour, Yuval G Noach, Uri Yoel, Marina Rosengarten-Levin, Oleg Zilber, Alon Zemer, Habib Muallem, Vered Chalifa-Caspi, Danit R Shahar, Idit F Liberty, Nur Elkarnawi, Oleg Dukhno, Idan Carmeli, Ran Orgad, Yulia Haim, Assaf Rudich.

   CONTEXT: Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10-25% of all MBS and is commonly-performed for weight regain after prior significant weight-loss. It remains unclear how adipose tissue adapts to surgically-induced weight-loss-regain in obesity.
OBJECTIVE: We hypothesized that compared to primary bariatric surgery (p-BS), women undergoing r-BS exhibit a distinct adipose tissue signature.
DESIGN: Subcutaneous/visceral adipose tissues (SAT/VAT, respectively) from female MBS patients were assessed histologically/molecularly/functionally (activation of human microglia cells by SAT-secretome).
SETTING: Elective MBS in a public university hospital.
PATIENTS: Women undergoing either p-BS, or r-BS with documented >15% weight-loss after prior MBS.
INTERVENTION: MBS.
MAIN OUTCOME MEASUREMENT: Inflammation in SAT.
RESULTS: Women undergoing r-BS (n=21) trended to be older than those undergoing p-BS (n=35)(47.2 vs. 40.5y, p=0.06), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters (fasting insulin, CRP and HDL-c). Adipocyte size, adipose tissue fibrosis, macrophage and crown-like structures abundance were similar, while mast-cells were slightly more prevalent in r-BS. Single-nucleus RNA-seq-based deconvolution algorithm applied unto bulk RNA-seq confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, RNA-seq revealed unique transcriptome of r-BS SAT, with activation of inflammatory pathways. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFκB-regulated cytokines IL6/IL8. Functional impact of the more inflammatory-secretome was suggested by its increased ability to inflammatory-activate human microglia cells.
CONCLUSIONS: Prior BS-induced weight-loss and subsequent regain in women is associated with inflammatory transcriptome and secretome of SAT that can activate cultured human microglia cells.

Keywords:  adipose tissue; bariatric surgery; inflammation; obesity; transcriptomics; weight regain

DOI:  https://doi.org/10.1210/clinem/dgag447
Physiol Rep. 2026 Nov;pii: e71160. [Epub ahead of print]14(21):

Acute sprint exercise transcriptome in adipose tissue of healthy adults: Associations with growth hormone.

Mona Esbjörnsson, Håkan C Rundqvist, Barbara Norman, Ted Österlund, Jens Bülow, Eva Jansson.

  We hypothesised that acute sprint exercise induces changes in adipose tissue (AT) gene expression related to lipolysis, and that growth hormone (GH) contributes to this. Healthy males and females were randomised to perform 3 × 30-s all-out cycle sprints (SIT, N = 12) or unloaded cycling (CON, N = 6). AT-biopsies were performed before and 2 h after exercise. Serum GH-response was greater following SIT than CON, but no SIT-specific enrichment of lipolysis-related genes was found in a genome-wide analysis. The hypothesis was partially supported. First, a group interaction was observed for the exercise-induced change in GH-receptor mRNA. Second, exercise-induced changes in the pre-selected lipolysis- and GH-related genes CISH, PTEN and G0S2 were associated with circulatory GH. In addition, in the genome-wide analysis, changes in expression of ARHGAP24, TAF4B, ARID5B, MIR604 and MIR938 were associated with GH-response. These genes have previously been found to be linked to AT-metabolism. Among the most downregulated genes were core clock genes, which decreased independently of loading and likely explained by diurnal regulation. Sex influenced both the rate of GH-response to exercise and the GH-responsive gene CISH. This reinforces, from a molecular perspective, the importance of controlling for diurnal variation and sex in exercise studies on regulation of AT lipolysis.

Keywords:  biopsy; high intensity; microarray analysis; sprint interval exercise; subcutaneous white adipose tissue; transcriptome

DOI:  https://doi.org/10.14814/phy2.71160
Compr Physiol. 2026 Dec;16(6): e70296

Circulating Plasma Adiposomes as a Partial Lipidomic Readout of Matched Subcutaneous Adipose Tissue: Implications for Interorgan Communication.

Mohamed Saad Rakab, Imaduddin Mirza, Elsayed Metwally, Mohammed Morsy, Carlos Martinez, Mario Masrur, Chandra Hassan, Francesco M Bianco, Brian T Layden, Abeer M Mahmoud.

   Background: Prior studies established adipose-derived extracellular vesicles, or adiposomes, as mediators of interorgan communication with lipidomic signatures linked to cardiometabolic health. Because adiposomes signal to distant organs via the circulation, we examined whether circulating adiposome lipidomes reflect matched subcutaneous adipose tissue adiposomes.
Methods: This cross-sectional paired lipidomic study included 22 subjects with matched circulating and subcutaneous adipose tissue adiposome samples. Untargeted lipidomics quantified 773 lipid features across 18 detected broad classes. Spearman correlation was the primary across-subject species-level metric; pooled and within-subject Pearson and Spearman correlations, principal component analysis, Bland-Altman analysis, class composition, and matched-versus-mismatched similarity were complementary measures. Additional analyses evaluated sex, cardiometabolic phenotypes, and focused species-clinical associations.
Results: Across 770 species with valid across-subject estimates, the median plasma-subcutaneous Spearman ρ was 0.101 and no species survived Benjamini-Hochberg false-discovery-rate correction, although 553 (71.8%) correlations were positive. Mean broad-class composition was highly conserved (Spearman ρ = 0.996; Pearson r on log2 percentages = 0.996). Matched whole-profile similarity was not greater than mismatched similarity (median ρ = 0.818 vs. 0.811; p = 0.620), and the matched sample was the closest pair for 0 of 22 participants. Neither sex nor any prespecified cardiometabolic phenotype explained matched-profile similarity after correction, and no focused species-clinical association survived full-screen FDR correction.
Conclusions: Circulating and subcutaneous adiposome lipidomes share a highly conserved mean class architecture, but individual species, subject-specific matching, and clinical-association patterns are not interchangeable. Plasma adiposomes may therefore serve as complementary circulating readouts of adipose-derived interorgan lipid signaling rather than direct tissue substitutes.

Keywords:  adipose tissue; adiposomes; cardiometabolic disease; circulating biomarkers; concordance; extracellular vesicles; interorgan communication; lipidomics; obesity

DOI:  https://doi.org/10.1002/cph4.70296
Mol Metab. 2026 Oct 31. pii: S2212-8778(26)00152-3. [Epub ahead of print] 102468

Differentiated obesity treatment: Pharmacological CRF2 agonism drives fat loss, skeletal muscle hypertrophy and improved glucose metabolism in preclinical obesity.

Kristoffer Niss, Sofia Lundh, Rucha Patel, Johannes Josef Fels, Albrecht Gruhler, Suzi Høgh Madsen, Fabrice Chimienti, Sarah Bau, Dennis Åsberg, Lennart Lykke, Nick Cox, Birgitte S Wulff, Nikolaj Kulahin Roed, Chien Li, Berit Ø Christoffersen.

   OBJECTIVE: Loss of lean mass during weight reduction may compromise metabolic health and physical function. Urocortin 2 (UCN2) activates corticotropin-releasing factor receptor 2 (CRF2) and has been linked to beneficial effects on skeletal muscle and glucose metabolism. We evaluated an acylated UCN2 analogue (acyUCN2), alone or combined with an acylated GLP-1 analogue (acyGLP-1), in preclinical obesity models.
METHODS: Diet-induced obese (DIO) Sprague Dawley rats and DIO Göttingen Minipigs were treated with vehicle or acyUCN2 (rats, pigs) or acyGLP-1 or combination therapy (rats only). Food intake, body weight (BW), body composition, glucose tolerance and energy expenditure (rats only) were assessed. Histology and RNA-sequencing were used to characterize muscle remodelling and transcriptional responses.
RESULTS: In rats, acyUCN2 reduced food intake and fat mass, increased lean mass and muscle weight, and improved glucose tolerance despite limited effects on BW. Energy expenditure was not affected. Histology demonstrated hypertrophy across fibre types and a shift from type 2A to type 2X/B fibres. Transcriptomic analyses supported muscle growth and fibre type switch, relative reduced vasculature, regulation of neuromuscular junction-associated genes, and overlap to human acute exercise-response signatures. In obese minipigs, acyUCN2 increased lean mass and improved insulin sensitivity, with modest effects on BW and fat mass, alongside regulation of genes linked to muscle biology and metabolism.
CONCLUSIONS: Pharmacological CRF2 agonism promotes favourable body composition, muscle hypertrophy, and improved glucose metabolism despite limited weight loss, supporting clinical development of UCN2 analogues as a differentiated obesity treatment, particularly in combination with appetite-regulating therapies and in settings where preservation of functional muscle mass is critical.

Keywords:  CRF2 agonism; Glucose metabolism; Muscle hypertrophy; Neuromuscular junction; Obesity; Skeletal muscle fibre remodelling; Transcriptomics; Urocortin 2

DOI:  https://doi.org/10.1016/j.molmet.2026.102468
Circ Genom Precis Med. 2026 Nov 04. e005465

Comparative and Sex-Specific Assessment of Proteomics, Clinical, and Genomic Data on Visceral Adipose Tissue Volume Using Machine Learning in UK Biobank: Advancing Precision Medicine.

Zahra Azizi, Trisha Gupte, Pik Fang Kho, Jiayan Zhou, Kevin Nzenkue, Rodrigo Guarischi-Sousa, Daniel J Panyard, Ming-Li Chen, Fahim Abbasi, Shoa L Clarke, Joshua W Knowles, Philip S Tsao, Themistocles L Assimes.

   BACKGROUND: Visceral adiposity is a key driver of insulin resistance, which in turn is a strong risk factor for type 2 diabetes and cardiovascular diseases.
METHODS: We investigated the overall and sex-specific associations between plasma proteomics and visceral adipose tissue volume, and their intersection with clinical and genomic data to identify critical candidate proteins for visceral adiposity possibly linked to insulin resistance. We analyzed data from UK Biobank participants, using multistep machine learning to establish linear and nonlinear associations.
RESULTS: The combined model, integrating clinical, proteomic, and polygenic data, accounted for 67% of visceral adipose tissue variance. Our research revealed significant protein interactions with environmental factors and identified sex-specific proteins correlated with visceral adipose tissue variance in both males and females.
CONCLUSIONS: The findings suggest that a small number of plasma proteins explain a significant portion of the variance of visceral adipose tissue beyond nonproteomic measures, offering a potential single-source, personalized measurement of visceral adiposity that is easily accessible and may facilitate improved prediction and understanding of the biology of insulin resistance.

Keywords:  UK Biobank; genomics; insulin resistance; machine learning; proteomics; sex differences; social determinants of health

DOI:  https://doi.org/10.1161/CIRCGEN.125.005465
FASEB J. 2026 Nov 15. pii: e72431. [Epub ahead of print]40(21):

Short-Term Unacylated Ghrelin Administration Improves Pyruvate Tolerance Without Chronically Altering Skeletal Muscle, Liver, or Adipose Tissue Insulin Response in Healthy Rats.

Nicole M Notaro, Sofia F Prizio, Brielle R Caruso, David J Dyck.

  Unacylated ghrelin (unAG) is a metabolically active hormone, acutely stimulating fatty acid oxidation in skeletal muscle while promoting lipogenesis and inhibiting lipolysis in adipose tissue. Given these acute effects, we hypothesized that repeated unAG administration would improve skeletal muscle insulin response and that this would be associated with reduced muscle lipid storage. We treated healthy male Sprague-Dawley rats with twice-daily subcutaneous unAG (200 μg; 400 μg total daily) for 5 days. UnAG treatment did not alter glucose uptake or AKT activation basally, or in response to low or high insulin concentrations when assessed ex vivo in oxidative or glycolytic skeletal muscle, or when muscle was pre-exposed to a high-palmitate stress. Protein content of mitochondrial markers (CPT1B, citrate synthase, COXIV) also remained unchanged with treatment in both muscle types. Interestingly, UnAG-treated animals had a reduced glycemic response to pyruvate administration; however, content of hepatic glucose production-associated proteins and liver AKT response to insulin remained unchanged. UnAG treatment tended to increase LPL protein content in visceral adipose tissue (p = 0.07), but did not alter AKT or HSL phosphorylation in response to an insulin bolus in either subcutaneous or visceral adipose tissue. Finally, triacylglycerol content in the red and white gastrocnemius muscle, as well as in the liver, was unchanged by unAG administration. Overall, these findings indicate that short-term unAG treatment improves pyruvate tolerance, but that it does not exert persistent metabolic changes to skeletal muscle, liver, or adipose tissue substrate metabolism in healthy rats.

Keywords:  adipose tissue; gluconeogenic proteins; glucose uptake; insulin signaling; lipolytic proteins; liver; skeletal muscle; unacylated ghrelin

DOI:  https://doi.org/10.1096/fj.202604205R
iScience. 2026 Nov 20. 29(11): 118086

Fine mapping of early adipogenesis identifies committed progenitors with dual white and beige potential.

Sarah Hazell Pickering, Damien Dufour, Natalia M Galigniana, Philippe Collas, Nolwenn Briand.

  Thermogenic capacity in adipose tissue varies among individuals and declines with age, obesity, and insulin resistance. To investigate the cellular basis of this variability, we performed parallel white and beige adipogenic differentiation using subcutaneous adipose progenitors from six healthy subjects. Beige adipogenesis elicits subject-specific, UCP1-dependent, and non-canonical thermogenic programs. Single-cell transcriptomics reveals varied proportions of progenitor populations, defined by differential expression of extracellular matrix, cell adhesion, and cytoskeletal genes. Mapping adipogenic commitment uncovers a continuum of transcriptional states largely shared between white and beige differentiation. Within this continuum, we identify ICAM1-positive committed progenitors contributing to both white and beige phenotypes. Beige induction increases the proportion of structural adipose tissue-resident cells with distinct extracellular matrix signatures, suggesting that early microenvironmental remodeling primes plasticity in mature cells. These results support a model in which diverse adipocyte fates arise from plastic progenitors, with individual differences in thermogenic adaptation driven by genetic, environmental, and epigenetic factors.

Keywords:  adipogenesis; beige adipocyte; beiging; human adipose stem and progenitor cells; single-cell RNA-seq; thermogenesis

DOI:  https://doi.org/10.1016/j.isci.2026.118086
Aging Cell. 2026 Nov;pii: e70794. [Epub ahead of print]25(11):

MKP-2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice.

Morgan Welch, Nabin Ghimire, Shauri Smith, Cassandra Secunda, Alexis Fink, Alissar Sleiman, Laura Chambliss, Christopher Pinckard, Chloe Reyes, Priya Katta, Anna Ai, Benjamin R Harrison, Ahmed Lawan.

  Aging is characterized by a gradual decline in physiological functions, impaired cellular repair mechanisms, and increased disease susceptibility. Mitogen-activated protein kinase phosphatase-2 (MKP-2) regulates diverse biological functions, including regulation of infection, brain activity, nutrient metabolism, and cell-cycle progression, but its role in senescence and adipose lipid metabolism in vivo remains unclear. Here, we investigated the effects of MKP-2 deficiency on cellular senescence and adipose lipid composition in aged mice using targeted lipidomics. MKP-2-deficient mouse embryonic fibroblasts (MEFs) and epididymal white adipose tissue (EWAT) exhibited reduced premature senescence. Lipidomic analysis revealed increased hexosylceramides (HexCERs) and phosphatidylglycerols (PG), and decreased diacylglycerols (DGs) in adipose tissue. These lipid alterations were accompanied by preserved lamin B1, reduced p53 phosphorylation, p16, and PAI-1, and increased JNK and Akt phosphorylation in EWAT. MKP-2 deficiency was also associated with extended lifespan and enhanced insulin responsiveness. Together, these studies identify MKP-2 as a potential regulator linking adipose lipid metabolism, stress-responsive signaling, cellular senescence, and aging, with its loss promoting a metabolically resilient adipose state that may contribute to improved systemic health and lifespan.

Keywords:  MAPK; MKP‐2; adipose tissue; aging; senescence

DOI:  https://doi.org/10.1111/acel.70794
Am J Physiol Endocrinol Metab. 2026 Nov 02.

Tissue-Specific Regulation of Glucose and Lipid Metabolism by miR-29a in Insulin Resistance and Type 2 Diabetes.

Mariazel Rubio-Valles, Brendan Egan, Everardo Gonzalez-Rodriguez, Verónica Moreno-Brito, Rosa P Hernández-Torres, Ángel G Díaz-Sánchez, Jorge A Pérez-León, Isaac A Chavez-Guevara, Arnulfo Ramos-Jiménez.

  MicroRNA-29a (miR-29a) has emerged as a context-dependent regulator of glucose and lipid metabolism in insulin-sensitive tissues, yet its tissue-specific actions in insulin resistance and type 2 diabetes remain incompletely understood. We synthesized peer-reviewed evidence retrieved from PubMed, Scopus, Web of Science, and EBSCOhost on the role of miR-29a across skeletal muscle, adipose tissue, liver, and pancreatic β-cells. We first define the nomenclature and genomic organization of the miR-29 family, its upstream transcriptional regulators, and the Argonaute-based evidence that separates direct target repression from correlative association. Across these tissues, miR-29a modulates oxidative metabolism, inflammatory signaling, and mitochondrial adaptation, largely through the PPARδ/PGC-1α axis, exerting complex and sometimes opposing effects depending on the tissue environment. We further examine miR-29a as a mediator of interorgan communication through extracellular vesicles, its responsiveness to exercise, and its emerging value as a biomarker and therapeutic target, while highlighting unresolved contradictions and translational hurdles. Because miR-29 family members act as tumor suppressors in most epithelial tissues, we also address the oncogenic risk inherent in nucleic acid strategies that lower miR-29a levels. Collectively, this mini-review positions miR-29a as a physiology-oriented integrator of metabolic remodeling and tissue-specific adaptation in metabolic disease.

Keywords:  exercise; extracellular vesicles; insulin resistance; microRNA-29a; mitochondrial metabolism; type 2 diabetes mellitus

DOI:  https://doi.org/10.1152/ajpendo.90160.2026
Metabolism. 2026 Nov 02. pii: S0026-0495(26)00332-X. [Epub ahead of print] 156819

Multi-target phosphodiesterase inhibition overcomes adipose catecholamine resistance and ameliorates systemic lipotoxicity.

Tamami Fujiki, Jun Takami, Kensuke Ihara, Kohei Kawajiri, Ryosuke Ishida, Kanako Nagaoka, Yutaro Mori, Yuma Waseda, Soichiro Yoshida, Shintaro Mandai, Takayasu Mori, Koichiro Susa, Shingo Sato, Shingo Kajimura, Hiroyuki Kagechika, Tetsuo Sasano, Yasuhisa Fujii, Eisei Sohara, Shinichi Uchida, Makoto Arita, Fumiaki Ando.

  Obesity-related adipose tissue dysfunction is characterized by reduced β3-adrenergic receptor (β3AR) expression, resulting in impaired catecholamine-dependent lipolysis and limiting the efficacy of β3AR agonists. The discovery of impaired β3AR/cyclic adenosine monophosphate (cAMP) signaling caused by concurrent β3AR downregulation (limiting cAMP production) and phosphodiesterase 4 (PDE4) upregulation (enhancing cAMP degradation) necessitated the development of TMDU-3 as a multi-isoform PDE inhibitor targeting PDE4, PDE1, PDE3, and PDE10. TMDU-3 robustly restored downstream cAMP-mediated phosphorylation events, including lipolytic activation, and concomitantly increased upstream β3AR expression in white adipose tissue (WAT) from obese mice. Despite a 5-fold increase in WAT mass, TMDU-3 normalized the WAT lipid composition. Moreover, TMDU-3 enhanced thermogenesis in brown adipose tissue, corrected serum accumulation of various lipids, and more effectively reduced circulating monounsaturated fatty acids than the β3AR agonist mirabegron. These findings demonstrate that multi-target PDE inhibition represents a β3AR-independent strategy superior to β3AR agonism in ameliorating obesity-associated metabolic dysfunction.

Keywords:  Catecholamine resistance; Lipotoxicity; Obesity; Phosphodiesterase; cAMP signaling; β3-Adrenergic receptor

DOI:  https://doi.org/10.1016/j.metabol.2026.156819
Sci Adv. 2026 Nov 06. 12(45): eaee1641

A transcriptional and cellular exploration of obesity and type II diabetes in human adipose tissues.

William V Trim, Kseniia Petrova, Katie Healy, Brenneth M Stevens, John G Scanlan, Heather J Faust, Sara Svensson Akusjärvi, Katie L O'Brien, Donal O'Shea, Michael B Brenner, Helen Heneghan, Lydia Lynch.

Obesity is tightly linked to metabolic disorders such as type II diabetes mellitus (T2D), although a subpopulation of individuals with obesity do not present with these morbidities. The biological factors conferring T2D vulnerability remain incompletely understood. We recruited 58 individuals with obesity with or without a clinical diagnosis of T2D (Ob + T2D and Ob). We profiled paired samples of omental and subcutaneous adipose by single-cell RNA sequencing (n = 10), flow cytometry under basal and stimulated conditions (n = 42), and histology (n = 17). Flow cytometry and chemokine quantification were also performed in paired whole blood. We identified reprogramming of the omental stromal compartment, centered on mesothelial and endothelial cells, alongside contrasting innate T cell and macrophage phenotypes across depots. Mesothelial and IGFBP2+ cells exhibited a fibrotic, epithelial-mesenchymal transition-like phenotype, while omental endothelial cells exhibited a lipid-overload, inflammatory, antigen presentation profile in T2D. Omental and subcutaneous adipose innate T cells exhibited divergent inflammatory profiles between tissues. These findings reveal previously unidentified insights into the pathophysiology of T2D in adipose tissue and identify compensatory networks within the tissues that could be exploited by targeted therapeutics.

DOI: https://doi.org/10.1126/sciadv.aee1641