bims-mimead Biomed News
on Adipose tissue and metabolic disease
Issue of 2026–08–30
eight papers selected by
Rachel M. Handy, University of Guelph and Universiteit Mastricht
  1. Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial.
  2. Interleukin-19 Regulates Adipose Tissue Dysfunction in Obesity: Interplay Between Inflammation and Vascularization.
  3. Loss of mitochondrial co-chaperone GRPEL2 protects mice from age- and diet-induced obesity.
  4. Lactose and Sucrose Each Stimulate Hepatic De Novo Lipogenesis: A Randomised Crossover Trial.
  5. Human Brown Fat Metabolism Associates with Systemic Branched-Chain Amino Acids Homeostasis.
  6. Assessing the physiology of weight loss based on real-time weight monitoring: The ADAPT behavioral weight loss study protocol.
  7. Chronic low-dose of BPS and PFOS alter adipogenic programming and impair insulin responsiveness in human adipocytes.
  8. Network Model to Predict Age-Related Transcriptional Reprogramming.
  1. Cell Metab. 2026 Aug 27. pii: S1550-4131(26)00293-7. [Epub ahead of print]
    Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial.
    Max C Petersen, Gordon I Smith, Sarah S Farabi, Hector H Palacios, Mahalakshmi Shankaran, Marc K Hellerstein, Bruce W Patterson, Samuel Klein.
      The influence of diet macronutrient content on the cardiometabolic effects of weight loss in people with metabolically unhealthy obesity (prediabetes and hepatic steatosis) has important clinical implications. We evaluated the cardiometabolic effects of moderate (∼10%) weight loss induced by three popular diets with markedly different macronutrient composition (very-low-carbohydrate ketogenic, Mediterranean, and very-low-fat plant-forward). Weight loss increased muscle insulin sensitivity by ∼50% in all groups but caused a two-to-three-fold greater increase in hepatic insulin sensitivity in the very-low-carbohydrate group than the other groups (p < 0.001). Intrahepatic triglyceride content, hepatic de novo lipogenesis, glycated hemoglobin, and 24-h serial plasma glucose and insulin decreased most in the very-low-carbohydrate group. There were no differences among groups in LDL-cholesterol, apolipoprotein B, or 24-h plasma triglyceride concentrations. These results demonstrate that a very-low-carbohydrate diet has greater cardiometabolic benefits, particularly in hepatic metabolic function, than matched 10% weight loss induced by a Mediterranean or very-low-fat diet in people with metabolically unhealthy obesity.
    Keywords:  MASLD; Mediterranean diet; carbohydrate; fat; insulin resistance; ketogenic diet; macronutrient; nutrition; obesity; plant-forward diet
    DOI:  https://doi.org/10.1016/j.cmet.2026.07.020
  2. FASEB J. 2026 Aug 31. 40(16): e72242
    Interleukin-19 Regulates Adipose Tissue Dysfunction in Obesity: Interplay Between Inflammation and Vascularization.
    Christine N Vrakas, Tatsuo Kawai, Mitali Ray, Allison B Herman, Zeinab Etwebi, Sheri E Kelemen, Rosario Scalia, Michael V Autieri.
      Expanding visceral white adipose tissue (WAT) becomes hypoxic due to lack of compensatory vascularization. Hypoxia initiates inflammation, presumably to promote angiogenesis. Unfortunately, in obesity this results in adipocyte dysfunction and related cardiometabolic complications due to chronic low-grade inflammation. We hypothesize that IL-19 acts as a vascular and immunometabolic protective adipokine in obesity. We report that IL-19 is expressed in WAT. Utilizing lean Il19-/- knockout mice, we found that IL-19 deficiency causes significantly reduced tissue vascularization, significantly increased adipose tissue hypoxia, fibrosis, and inflammation, as well as adipocyte hypertrophy. Moreover, lean Il19-/- knockout mice fed a standard diet developed glucose intolerance and insulin resistance. Wild-type mice with diet-induced obesity also developed reduced vascularization and inflammation in WAT, along with glucose intolerance and insulin resistance. Treatment of wild-type obese mice with recombinant IL-19 improved vascularization, attenuated WAT inflammation, and reduced glucose intolerance. Mechanistic studies in vitro demonstrated that IL-19 increases glucose uptake in cultured adipocytes, including human adipocytes. These metabolic actions of IL-19 were linked to upregulation of the IRS2 and GLUT-4 expression and function. Overall, these data are the first to demonstrate that endogenous anti-inflammatory interleukins can be effectively used to uncouple inflammation from angiogenesis, thus preserving WAT metabolic function in obesity.
    Keywords:  adipose tissue; angiogenesis; inflammation; interleukin‐19; obesity
    DOI:  https://doi.org/10.1096/fj.202502231R
  3. Mitochondrion. 2026 Aug 22. pii: S1567-7249(26)00095-4. [Epub ahead of print]91 102205
    Loss of mitochondrial co-chaperone GRPEL2 protects mice from age- and diet-induced obesity.
    Yang Yang, Nirajan Neupane, Jouni Kvist, Jonna Saarimäki-Vire, Matthias Schewe, Kalle Luopajärvi, Pooja Manjunath, Svetlana Konovalova, Rubén Torregrosa-Muñumer, Veijo Kinnunen, Pekka Katajisto, Timo Otonkoski, Eija Pirinen, Jayasimman Rajendran, Henna Tyynismaa.
      Mitochondrial protein homeostasis intersects with metabolic control, but the in vivo roles of specific mitochondrial co-chaperones remain unclear. The chaperone mtHSP70 plays a key role in import and folding of nuclear-encoded proteins targeted to mitochondrial matrix. Its protein folding cycle is regulated by the GrpE-like nucleotide exchange factor GRPEL1. Vertebrates also have a GRPEL2 paralog, postulated as the stress-sensitive counterpart, but its physiological relevance is not known. We show here that GRPEL2 is not essential for viability in mice, and its absence does not induce proteotoxic stress responses in stark contrast to GRPEL1. However, we find that GRPEL2 has a role in regulating body weight homeostasis. GRPEL2 knockout mice are protected from age- and diet-induced weight gain and maintain a better metabolic health and insulin sensitivity. Transcriptional profiling revealed minimal changes in liver and skeletal muscle, whereas white adipose tissue from Grpel2-deficient mice lacked the obesity-associated remodeling seen in controls. We propose that GRPEL2 fine-tunes metabolic setpoints without broadly perturbing mitochondrial protein import, thereby maintaining adipose tissue health during nutritional excess. These findings show that subtle alterations in mitochondrial chaperone systems reshape systemic metabolism and could suggest strategies to mitigate obesity and insulin resistance through targeted modulation of mitochondrial proteostasis.
    Keywords:  Adipose tissue; Body weight homeostasis; Grpel2; Mitochondrial protein import; Nucleotide exchange factor; mtHSP70
    DOI:  https://doi.org/10.1016/j.mito.2026.102205
  4. Am J Clin Nutr. 2026 Aug 25. pii: S0002-9165(26)00301-1. [Epub ahead of print] 101492
    Lactose and Sucrose Each Stimulate Hepatic De Novo Lipogenesis: A Randomised Crossover Trial.
    Steven Carter, Bruno Spellanzon, Elspeth Johnson, Francoise Koumanov, Kaitlyn M J H Dennis, Coco A Taylor Start, Louise Bradshaw, Alfonso Moreno-Cabañas, Lucy H Merrell, Emma E Vincent, Benedita Deslandes, Jennifer L Maher, Matthew J Neville, James A Betts, Dylan Thompson, Leanne Hodson, Javier T Gonzalez.
       BACKGROUND: Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) relative to glucose-based carbohydrates. Despite being consumed by most of the global population, the effects of galactose-containing sugars on hepatic DNL are currently unknown.
    OBJECTIVE: To assess the effects of lactose ingestion on lipaemia and DNL.
    METHODS: Twenty-four adults without obesity (12 male and 12 female) completed three laboratory visits in a randomised, crossover design (33±14-day washout; mean±SD). During laboratory visits, participants consumed beverages containing 50g fat with 100g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Summary statistics were analysed by one-way ANOVA, and time series data by two-way (time x treatment) ANOVA or linear mixed models when data were missing.
    RESULTS: The plasma triacylglycerol iAUC (mean±SD) in response to maltodextrin was 0.85±1.13mmol·L-1·360 min and peak hepatic DNL was 11±3%. Following lactose ingestion, plasma triacylglycerol iAUC increased to 1.63±1.47mmol·L-1·360 min (p<0.001 versus maltodextrin), and hepatic DNL increased to 22±4% (p<0.001 versus maltodextrin), to a degree statistically indistinguishable from following sucrose ingestion [1.50±1.58mmol/L-1·360 min (p=0.41 versus lactose); and 23±4% (p=0.54 versus lactose)]. Contributions of dietary fat to VLDL- and Chylomicron-TG-palmitate were both higher following ingestion of lactose versus maltodextrin (both p<0.05), and were statistiscally indistinguishable following lactose ingestion versus sucrose (both p>0.05).
    CONCLUSIONS: Lactose ingestion stimulates hepatic DNL by a magnitude that is not statistically different from fructose. This challenges the prevailing view that galactose-containing sugars are metabolically equivalent to glucose-based carbohydrates.
    CLINICAL TRIALS REGISTRATION: NCT04924530 (https://clinicaltrials.gov/study/NCT04924530).
    Keywords:  Sugars; fructose; galactose; glucose; lipids; metabolism
    DOI:  https://doi.org/10.1016/j.ajcnut.2026.101492
  5. Mol Metab. 2026 Aug 26. pii: S2212-8778(26)00118-3. [Epub ahead of print] 102434
    Human Brown Fat Metabolism Associates with Systemic Branched-Chain Amino Acids Homeostasis.
    Mueez U-Din, Francisco M Acosta, Teemu Saari, Vanessa D de Mello Laaksonen, Birgitta W van der Kolk, Milena Monfort-Pires, Mercedes Clemente-Postigo, Tarja Niemi, Markku Taittonen, Marjo Tuomainen, Tobias Fromme, Marko Lehtonen, Karsten Kristiansen, John W Newman, Kirsi H Pietiläinen, Jussi Pihlajamäki, Eija Pirinen, Martin Klingenspor, Kati Hanhineva, Juho Raiko, Kirsi A Virtanen.
      Circulating branched-chain amino acids (BCAAs) are linked with insulin resistance, but the human tissues contributing to systemic BCAA homeostasis remain incompletely defined. Brown adipose tissue (BAT) is a metabolically active adipose depot associated with favourable insulin sensitivity, yet its role in BCAA metabolism in humans remains unclear. We tested whether human BAT metabolism is associated with circulating BCAA levels, BAT-resident BCAA-catabolic signatures, and longitudinal changes in systemic BCAA homeostasis. We studied 83 adults who underwent metabolic phenotyping, PET-CT assessment of cold-stimulated BAT metabolism, and serum metabolomic profiling at room temperature and during acute mild cold exposure. Supraclavicular BAT biopsies from 25 participants were analysed by transcriptomics and metabolomics, and 40 participants were re-examined for circulating BCAA profiles after approximately five years. Participants with high BAT metabolism had lower circulating BCAA levels than those with low BAT metabolism. Within BAT, metabolically active individuals exhibited lower relative BCAA abundance together with higher expression of genes involved in BCAA catabolism. These BAT BCAA-catabolic signatures aligned with thermogenic capacity and indices of systemic insulin sensitivity. In contrast, individuals with low BAT metabolism showed increases in circulating BCAAs over five years. Integrative analyses further linked circulating lipopolysaccharide, a marker of metabolic endotoxemia, with higher BAT BCAA and aminomalonate abundance, together with transcriptional patterns involving inflammatory and mitochondrial pathways. Together, these findings identify human BAT metabolism as a tissue phenotype linked to systemic BCAA homeostasis and extend the role of human BAT beyond thermogenesis, suggesting that BAT-associated BCAA handling may contribute to systemic metabolic health.
    Keywords:  Branched-chain amino acids; Brown adipose tissue; Insulin resistance
    DOI:  https://doi.org/10.1016/j.molmet.2026.102434
  6. PLoS One. 2026 ;21(8): e0354678
    Assessing the physiology of weight loss based on real-time weight monitoring: The ADAPT behavioral weight loss study protocol.
    Susan J Melhorn, Ana P Valencia, Jeannette M Schenk, Jose M Garcia, Sarah J Beatty, Anne Konchan, Arthur F Brandao, Natalia L Acosta-Vega, David J Marcinek, Jenny Tong, Marian L Neuhouser, Ellen A Schur.
      Improving health outcomes via sustained weight loss and maintenance requires advancing understanding of the metabolic, appetitive, and neurological alterations that counteract-and eventually halt-weight loss. Prior studies have demonstrated increased appetite as well as metabolic adaptations, such as increased energy efficiency, in response to weight loss. However, previous study designs utilized experimentally determined weight loss plateaus and did not investigate spontaneously occurring plateaus nor study participants in their natural, free-living, environments during weight loss. The Assessing Diet, Appetite, and Physiology Throughout weight loss (ADAPT) study was designed to address these limitations of prior research and elucidate mechanistic factors involved in spontaneous cessation of intentional weight loss in humans. ADAPT enrolls participants with obesity who undergo behavioral weight loss via a reduced calorie diet and increased physical activity. Participants' daily weight is monitored remotely, and new analytic approaches identify weight-loss phases in real time so that study assessments can be targeted to each participants' individualized trajectory during dynamic weight loss. Deep phenotyping of participants includes anthropometric, metabolic, neurophysiologic, and behavioral assessments; physical activity and physiologic monitoring via wearable devices; and serial sampling of biological tissues such as blood, adipose tissue, and muscle. In summary, the ADAPT study design is generating a uniquely informative and integrative dataset for deepening understanding of the biological mechanisms that halt behaviorally-induced weight loss and thereby limit its long-term health benefits for patients with obesity. NCT06174389.
    DOI:  https://doi.org/10.1371/journal.pone.0354678
  7. J Endocrinol Invest. 2026 Aug 26.
    Chronic low-dose of BPS and PFOS alter adipogenic programming and impair insulin responsiveness in human adipocytes.
    Giulia Gaggi, Andrea Di Credico, Sandra Bibbò, Annalisa Marini, Angela Di Baldassarre, Barbara Ghinassi.
       BACKGROUND AND AIM: obesity is a major global health concern tightly linked to insulin resistance and type 2 diabetes. Environmental exposure to endocrine-disrupting chemicals (EDs), including bisphenols (BPs) and perfluoroalkyl substances (PFs), has been implicated in metabolic dysfunction, yet the impact of chronic low-dose co-exposure on human adipocyte development and insulin responsiveness remains poorly defined. Here, we evaluated bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or combined, in human adipose-derived stem cells undergoing adipogenic differentiation.
    METHODS: Cells were chronically exposed to environmentally relevant low doses of bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or in combination, throughout adipogenic differentiation.
    RESULTS: Lipid droplet accumulation was unchanged across conditions, indicating preserved terminal differentiation. In contrast, BPS and PFOS altered the timing and magnitude of key adipogenic transcriptional programs (CEBPA, PPARγ) and the mature adipocyte marker FABP4. PFOS and BPS+PFOS selectively increased IL1β expression in mature adipocytes, suggesting a limited pro-inflammatory shift. Functionally, all ED-treated groups showed reduced insulin-stimulated glucose uptake, associated with impaired GLUT4 translocation to the plasma membrane despite unchanged total GLUT4 levels. Notably, combined exposure produced the strongest defects in insulin signalling, reducing PI3K pathway activation and decreasing total AKT and ERK1/2 protein levels. In contrast, individually administered BPS and PFOS impaired glucose uptake without detectable PI3K alterations, suggesting the involvement of additional mechanisms.
    CONCLUSION: Overall, chronic low-dose exposure to BPS and PFOS disrupts adipocyte transcriptional and signalling networks, inducing features consistent with impaired insulin responsiveness and underscoring the importance of considering ED mixtures in metabolic risk assessment.
    Keywords:  Adipogenesis; BPS; Endocrine disruptors; GLUT4; Insulin signalling; PFOS
    DOI:  https://doi.org/10.1007/s40618-026-03030-y
  8. Aging Cell. 2026 Sep;25(9): e70683
    Network Model to Predict Age-Related Transcriptional Reprogramming.
    Tyler J McNeill, Fabrisia Ambrosio, Hirotaka Iijima.
      Understanding how secreted factors from aged tissue, often referred to as the senescence-associated secretome, reshape cellular phenotypes remains a major challenge due to the complexity of downstream molecular cascades. Here, we present a computational framework for in silico perturbation modeling designed to predict distinct transcriptional responses to age-specific extracellular environmental cues. We exemplify applications of this framework using articular chondrocytes exposed to secretomes derived from infrapatellar fat pads-an integral component of the cartilage microenvironment-excised from the knee joints of young and aged animals. First, we accessed public transcriptomic data of cartilage from healthy and osteoarthritic knee joints and constructed a cartilage-specific co-expression network using topological overlap matrices, which measure network interconnectedness. We then implemented a Random Walk with Restart to simulate the downstream signal propagation of differentially expressed ligands secreted from young and aged infrapatellar fat pads. We benchmarked predicted perturbation signatures against RNA-seq data from aged chondrocytes treated in vitro with either young or aged infrapatellar fat pad-conditioned medium. Our evaluation pipeline included functional enrichment comparison and receiver operating characteristic analysis. These analyses confirmed that simulated perturbations recapitulated chondrocyte signaling pathways modulated by young and aged infrapatellar fat pad secretomes, including primary effects on mitochondrial respiration, a central hallmark of aging. The network paradigm introduced here provides a data-driven strategy to disentangle how complex, age-dependent extracellular environments influence cellular fate. Ultimately, we anticipate that this pipeline can be extended to diverse tissues and age-related diseases to guide the development of interventions that restore youthful cellular phenotypes.
    Keywords:  cell communication; extracellular signaling; gene expression profiling; in silico simulation; osteoarthritis
    DOI:  https://doi.org/10.1111/acel.70683
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