bims-mimead Biomed News
on Adipose tissue and metabolic disease
Issue of 2026–02–08
seven papers selected by
Rachel M. Handy, University of Guelph
  1. Weight Loss Reduces IMAT and Liver Fat Compared to Exercise: Implications for Muscle Quality and Metabolic Health.
  2. NLRP3-Caspase-1 Axis in Human Adipose Tissue Crown-Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery.
  3. Identification of a New Transcriptional Signature of Pre-Adipocytes in Human Subcutaneous White Adipose Tissue.
  4. Substrate Utilization During Short-Term Fasting in Older Men and Women.
  5. In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds.
  6. Proteomic Profiling of Human Omental and Subcutaneous Adipose Tissue in Individuals with a Broad Range of BMI.
  7. Reduced glycoprotein hormone β-5 links male aging and testosterone decline to increased adiposity.
  1. J Clin Endocrinol Metab. 2026 Jan 31. pii: dgag018. [Epub ahead of print]
    Weight Loss Reduces IMAT and Liver Fat Compared to Exercise: Implications for Muscle Quality and Metabolic Health.
    Karin Zemski Berry, Amanda Garfield, Emily Macias, Simona Zarini, Sophia Bowen, Melanie G Cree, Janet K Snell-Bergeon, Stephan Bodkin, Bryan C Bergman.
       BACKGROUND: Weight loss improves insulin sensitivity and liver fat but reduces lean mass. Whether reductions in intermuscular adipose tissue (IMAT) exceed muscle loss and how these effects compare with endurance exercise training without weight loss remains unclear.
    METHODS: In a 12-week randomized intervention, forty-six individuals with obesity were assigned to weight loss (WL - age 39.7±1.3; BMI 35.2±0.9; W/M 8/9), endurance exercise training without weight loss (EX - age 39.7±1.6; BMI 36.0±1.1; W/M 8/8), or delayed-control intervention groups (age 39.8±1.4; BMI 36.8±1.3; W/M 6/7). Changes in IMAT volume, skeletal muscle mass, and liver fat measured by MRI; insulin sensitivity assessed by hyperinsulinemic-euglycemic clamp; and plasma lipidomics and metabolomics by LC-MS based methods.
    RESULTS: WL reduced body weight (-10.5%; p<0.001), liver steatosis (-33.1%; p<0.0001), and IMAT volume (-12.7%; p<0.0001), while improving insulin sensitivity (42%; p=0.004). IMAT decreased significantly more than skeletal muscle mass (-4.2%, p=0.17), indicating improved muscle quality. EX increased insulin sensitivity (23%; P=0.04) and VO₂peak (7.6%; p<0.001) but did not significantly change IMAT or liver fat. DXA overestimated muscle loss compared with MRI. WL decreased plasma sphingolipids and diacylglycerols, whereas EX reduced acylcarnitines. Plasma triacylglycerols and branched-chain amino acids were strongly correlated with liver fat, and triacylglycerols showed the strongest association with IMAT volume.
    CONCLUSIONS: Weight loss is more effective than endurance exercise training without weight loss for reducing IMAT and liver steatosis, with IMAT loss exceeding muscle loss. Plasma lipids and metabolites signatures are associated with liver fat and IMAT, supporting their potential utility as non-invasive biomarkers.
    Keywords:  Intermuscular adipose tissue; lipidomics; liver steatosis; muscle quality; obesity
    DOI:  https://doi.org/10.1210/clinem/dgag018
  2. Immun Inflamm Dis. 2026 Feb;14(2): e70312
    NLRP3-Caspase-1 Axis in Human Adipose Tissue Crown-Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery.
    Ville A Palomäki, Juha P Väyrynen, Vesa Koivukangas, Sanna Meriläinen, Tuomo J Karttunen, Petri Lehenkari.
       BACKGROUND: Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity.
    METHODS: Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up.
    RESULTS: Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures.
    CONCLUSIONS: Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.
    Keywords:  NLRP3; caspase‐1; crown‐like structures; inflammation; macrophage; obesity
    DOI:  https://doi.org/10.1002/iid3.70312
  3. Obesity (Silver Spring). 2026 Feb 03.
    Identification of a New Transcriptional Signature of Pre-Adipocytes in Human Subcutaneous White Adipose Tissue.
    Katie L Whytock, Adeline Divoux, Gilian Gunsch, Jia Nie, Jitendra S Kanshana, Mahesh K Basantani, Zana M Ross, Maria F Pino, Carley Glass, Nicholas Musi, Erin E Kershaw, Kristy Townsend, Steven R Smith, Lauren M Sparks.
       OBJECTIVE: White adipose tissue (WAT) expansion occurs through generation of new adipocytes from adipose progenitor cells (APC). The objective of this study was to characterize and validate a new transcriptional profile of APC.
    METHODS: Single-cell (sc)/nuclei (sn) RNA-Seq was performed on nuclei from whole WAT (n = 20), cells from WAT stromal vascular fraction (n = 5), and cultured APC in vitro (n = 8) using ICELL8 smart-Seq technology. Additional snRNA-Seq was performed on WAT using 10x genomic platform. Pseudotime analyses and differentiation of hiPSCs was used to track the temporal patterns of novel gene signatures. Immunohistochemistry was performed to validate a new marker.
    RESULTS: A pre-adipocyte population was found across the four independent datasets that expressed known pre-adipocyte markers (ZNF423 and DLK1) in addition to genes typically associated with neurogenes (DPP10, PTRPT, CTNNA2, NRXN3, CTNNA2, PTPRD, CNTNAP2 and RBFOX1). The expression of these genes were temporally regulated with adipocyte differentiation. Immunohistochemistry analyses confirmed these pre-adipocytes are located in the neurovascular niche of WAT but are not neurons or endothelial cells.
    CONCLUSIONS: This work has defined a new transcriptional signature of pre-adipocytes in human subcutaneuous WAT that are distinct from mesencyhmal stem cell populations and represent novel targets for WAT expansion.
    DOI:  https://doi.org/10.1002/oby.70135
  4. Am J Physiol Endocrinol Metab. 2026 Feb 04.
    Substrate Utilization During Short-Term Fasting in Older Men and Women.
    San Wang, Rita H Tsay, Danya Zhang, Naomi K Fukagawa.
      Older people are prone to involuntary fasting, but systematic assessment of their mobilization and oxidation of the three macronutrients during fasting has not been previously reported. Because of changes in body composition and metabolic regulatory pathways with aging, older people might have different kinetics of utilization of macronutrient stores during fasting than younger people. We measured body composition by dual-energy X-ray absorptiometry and studied the effects of a 36-hour fast on protein mobilization, lipolysis, glucose output, and protein, fat, and carbohydrate oxidation in 10 older (60-81 y) and 10 younger (18-35 y) healthy adults. A 36-hour fast induced a pronounced shift toward fat oxidation: in the postabsorptive state fat oxidation averaged 52-55% of resting energy expenditure (REE) and increased to 63-68% after fasting, with corresponding decreases in carbohydrate oxidation. Protein oxidation decreased with fasting but still contributed 16-18% of REE in older participants. For several metabolic variables (respiratory exchange ratio, glucose Ra, glycerol Ra, urea Ra, urea excretion, and percent of REE from carbohydrate and fat), we observed significant age×fasting interactions (P < 0.01). Younger adults exhibited larger decreases in glucose Ra and greater increases in markers of protein turnover (leucine Ra, urea production) and lipolysis, whereas older adults showed blunted glucose and leucine responses but maintained substantial protein oxidation. These age-related differences suggest that older adults rely relatively more on ongoing protein catabolism during short-term fasting, which may contribute to vulnerability to muscle loss during illness or prolonged inadequate intake.
    Keywords:  aging; fasting; stable isotope tracers; substrate oxidation; substrate rate of appearance
    DOI:  https://doi.org/10.1152/ajpendo.00530.2025
  5. iScience. 2026 Feb 20. 29(2): 114480
    In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds.
    Anita Wagner, Juulia H Lautaoja-Kivipelto, Kalle Pehkonen, Antti Hassinen, Minna Kuusela, Lisa Röttger, Elena Herbers, Anna Ioannidou, Sophia Mädler, Ina Rothenaigner, Soumya Srinivasan, Sini Laasonen, M Tanvir Rahman, Pinja Elomaa, Saija Kortetjärvi, Anneli Olsson, Olavi Ukkola, Kamyar Hadian, Matthias Mann, Hilkka Peltoniemi, Kirsi H Pietiläinen, Martin Klingenspor, Kirsi A Virtanen, Carolina E Hagberg, Eija Pirinen.
      Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, yet in vitro models to study adipocyte mitochondria remain limited. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks using thiazolidinedione-free medium. Matrigel embedding was incorporated into the protocol as it promoted mitochondrial network and respiration compared to scaffold-free conditions. Differentiated spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration, adiponectin secretion, and hormonal responsiveness. Lipid mixture administration during differentiation induced metabolic disturbances, including mitochondrial respiration failure, alongside increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria metabolism, providing a platform for mitochondria-focused research and drug discovery in obesity.
    Keywords:  Adipocyte; Human metabolism; Lipid; Mitochondria; Obesity; Spheroid
    DOI:  https://doi.org/10.1016/j.isci.2025.114480
  6. bioRxiv. 2026 Jan 15. pii: 2026.01.14.699533. [Epub ahead of print]
    Proteomic Profiling of Human Omental and Subcutaneous Adipose Tissue in Individuals with a Broad Range of BMI.
    Alex Zelter, Yue Winnie Wen, Michael Riffle, Lindsay C Czuba, Aprajita S Yadav, Jerry Zhu, Jessica M Snyder, Aaron Maurais, Jeffrey LaFrance, Saurabh Khandelwal, Judy Y Chen, Estell Williams, Zoe Parr, Daniel Kim, Katya B Rubinow, Michael J MacCoss, Nina Isoherranen.
      Obesity is a major public health challenge affecting an ever-increasing proportion of the global population. It is associated with numerous comorbidities. Progressive expansion and remodeling of adipose tissue may lead to depot specific changes in adipose tissue biology and energy partitioning. Such changes likely precede the development of obesity-related complications. To facilitate a deeper understanding of adipose tissue biology, a comprehensive and quantitative proteomic dataset at the peptide and protein level is presented. Data-independent acquisition LC-MS/MS data were acquired from matched subcutaneous and omental adipose tissues from metabolically healthy individuals with no comorbidities and covering a wide range of body mass indexes. Adipose tissue samples were collected during elective surgeries and immediately processed for histology or frozen until proteomic analysis. Internal and external quality control systems ensured high quality data. All data presented are available via ProteomeXchange. This dataset will allow new insights into biological changes that evolve with increasing adiposity captured before the onset of comorbidities. Matched sampling across fat depots provides an opportunity to uncover depot-specific physiological signatures.
    DOI:  https://doi.org/10.64898/2026.01.14.699533
  7. J Clin Invest. 2026 Feb 03. pii: e192355. [Epub ahead of print]
    Reduced glycoprotein hormone β-5 links male aging and testosterone decline to increased adiposity.
    Gengmiao Xiao, Aijun Qian, Zhuo Gao, Tingting Dai, Hui Liang, Shuai Wang, Mulan Deng, Yunjing Yan, Xindan Zhang, Xuedi Zhang, Yunping Mu, Jiqiu Wang, Aibo Gao, Huijie Zhang, Fanghong Li, Allan Zijian Zhao.
      Aging commonly causes decline of testosterone or estrogen, leading to overaccumulation of fatness in males or females, respectively. Although such phenomenon can be readily explained by estrogen's direct action on adipocytes in females, accumulative evidence does not support the direct action of testosterone in adipocyte lipid metabolism, suggesting that there is a missing intermediary link. Herein, we propose that glycoprotein hormone β5 (GPHB5) is the intermediary linkage between testosterone and the regulation of adiposity. In clinical samples, blood levels of GPHB5 were correlated negatively with men's ages, and positively with circulating testosterone. Testosterone directly stimulated the expression of GPHB5 in cultured cells, pharmacological blockade of androgen receptor (AR) functions abrogated such effect. Knockout of AR led to not only development of obesity but also reduction of GPHB5 expression. Genetic ablation of GPHB5 in the males, but not in the females, lowered the browning of white adipose tissue, diminished energy expenditure and caused severe obesity. Importantly, elevated blood testosterone didn't exert its catabolic actions in GPHB5 null mice, and yet, recombinant GPHB5 protein was able to stimulate energy expenditure and reduce adiposity. Taken together, these results provided the strong proof that GPHB5 is the "missing" intermediary hormone linking testosterone (and aging) and its well-known catabolic effect on adipose tissue.
    Keywords:  Adipose tissue; Aging; Endocrinology; Metabolism; Obesity; Sex hormones
    DOI:  https://doi.org/10.1172/JCI192355
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