bims-mimead Biomed News
on Adipose tissue and metabolic disease
Issue of 2025–07–06
nine papers selected by
Rachel M. Handy, University of Guelph
  1. Effects of Acute Iso- and Hypocaloric Carbohydrate Restriction on Liver Fat and Glucose and Lipid Metabolism.
  2. An Epigenome Atlas of Mouse Adipocytes.
  3. Lipid-associated macrophages are more abundant in subcutaneous than visceral adipose tissue in patients with obesity.
  4. Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice.
  5. β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes.
  6. TRIM59 deficiency aggravates HFD-induced obesity in mice associated with increased adipose tissue inflammation, lipid accumulation, and apoptosis.
  7. Metabolic Phenotypes, Genotypes, and Gut Microbiome Signatures in Obesity: Implications for Precision Nutrition Strategies in Type 2 Diabetes Prevention.
  8. Intestinal pH: a major driver of human gut microbiota composition and metabolism.
  9. Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes.
  1. J Clin Endocrinol Metab. 2025 Jul 02. pii: dgaf382. [Epub ahead of print]
    Effects of Acute Iso- and Hypocaloric Carbohydrate Restriction on Liver Fat and Glucose and Lipid Metabolism.
    Amalie London, Amanda Schaufuss, Michal Považan, Marie-Louise Dichman, Jasmin Merhout, Carsten Dirksen, Sten Madsbad, Hartwig Roman Siebner, Annemarie Lundsgaard, Andreas Mæchel Fritzen, Bente Kiens, Kirstine Nyvold Bojsen-Møller.
       CONTEXT: Liver fat is reduced within days after a low-carbohydrate diet substituted with fat to maintain isocaloric conditions.
    OBJECTIVE: Investigate the effect of matched carbohydrate restriction during isocaloric and hypocaloric conditions on liver fat and postprandial glucose and lipid metabolism.
    DESIGN: Cross-over randomized clinical trial.
    SETTING: Research unit.
    PARTICIPANTS: 15 participants with overweight/obesity (BMI 32.5 [31-34] kg/m2, median [IQR]).
    INTERVENTION: Three dietary interventions; 1) two days of isocaloric control diet (CON), 2) two days of CON followed by two days of carbohydrate-restriction (∼60 g/day) during very-low calorie conditions (VLCD), and 3) two days of CON followed by two days of isocaloric conditions with low carbohydrate (∼60 g/day), high-fat (LCHF) diet.
    MAIN OUTCOME MEASURE: Liver fat measured using 1H-magnetic resonance spectroscopy.
    RESULTS: Liver fat was -16% [-34;4] (median [IQR]) after LCHF relative to after CON (p=0.020), but did not differ between VLCD and CON. Fasting plasma concentrations of triacylglycerol, glucose, and insulin were lower after both LCHF and VLCD compared with after CON. However, postprandial plasma glucose concentrations were higher and insulinogenic index lower after both LCHF and VLCD.
    CONCLUSION: Two days of LCHF led to lower liver fat, which was not observed after VLCD. This demonstrates the dynamic regulation of liver fat and the beneficial role of substituting carbohydrates with fat to maintain energy provision. Both LCHF and VLCD had positive effects on fasting parameters for glucose metabolism, however, both diets impaired early beta-cell response resulting in deterioration in glucose handling during the meal test.
    Keywords:  MASLD (metabolic dysfunction-associated steatotic liver disease); glucose metabolism; lipid metabolism; low-carbohydrate; mixed meal test
    DOI:  https://doi.org/10.1210/clinem/dgaf382
  2. Mol Metab. 2025 Jun 27. pii: S2212-8778(25)00104-8. [Epub ahead of print] 102197
    An Epigenome Atlas of Mouse Adipocytes.
    Laura C Hinte, Adhideb Ghosh, Daniel Castellano-Castillo, Christian Wolfrum, Ferdinand von Meyenn.
       OBJECTIVE: Epigenetic modifications including histone post translational modifications can influence gene expression in adipocytes, potentially contributing to metabolic dysfunctions, obesity, and insulin resistance. Despite recent advances in the characterization of the mouse adipocyte epigenome, epigenetic characterization of adipocytes in vivo has been challenging, particularly across different adipose depots and of several epigenetic modifications.
    METHODS: Here, we use specific reporter mice labelling brown, beige and white adipocytes, diphtheria toxin-mediated ablation of beige adipocytes, and Cleavage Under Targets and Tagmentation (CUT&Tag) to generate paired single mouse datasets of five histone marks. We perform an integrative multi-omics factor analysis (MOFA) of H3K4me3, H3K27me3, H3K4me1, H3K27ac and H3K9me3 in brown, white and beige adipocytes from three distinct mouse adipose tissue depots obtained during cold exposure and thermoneutrality.
    RESULTS: Our analysis reveals that enhancers distinguish adipocytes by their tissue of origin, with H3K4me1 deposition differentiating between beige and brown adipocytes. Beige adipocytes poised promoters associated to thermogenic genes during warming. Diphtheria toxin-mediated ablation of beige adipocytes shows that non-beigeing white adipocytes in inguinal adipose tissue and beige adipocytes are not inherently epigenetically different suggesting that they share a common developmental progenitor.
    CONCLUSION: These paired multimodal data comprise an extensive resource (https://nme.ethz.ch/mAT_CEAtlas.html) for the further exploration of the mouse adipocyte epigenome which will enable discovery of regulatory elements governing adipocyte identity and gene regulation.
    Keywords:  Adipocytes; Beige; Brown; Enhancers; Epigenetics; Histone Marks; Multiomics; White
    DOI:  https://doi.org/10.1016/j.molmet.2025.102197
  3. Obesity (Silver Spring). 2025 Jun 29.
    Lipid-associated macrophages are more abundant in subcutaneous than visceral adipose tissue in patients with obesity.
    Marjorie Reyes-Farias, Pablo Fernández-García, Patricia Corrales, Lorena González, David Navarro-Sanagustín, Andrea Soria-Gondek, Silvia Pellitero, Jordi Tarascó, Pau Moreno, José M Balibrea, Laia Gatell, Lauro Sumoy, María Galán, Ester Martínez, Francesc Villarroya, Rubén Cereijo, Laura Herrero, David Sánchez-Infantes.
       OBJECTIVE: Because white adipose tissue is infiltrated by several immune cells and their signature in individuals with obesity has not been fully characterized, we wanted to study the most abundant population, which is macrophages, a subtype of myeloid cell.
    METHODS: To address this objective, we performed transcriptomic analysis of subcutaneous adipose tissue (SAT)- and visceral adipose tissue (VAT)-infiltrated CD11b+ myeloid cells from individuals with severe obesity.
    RESULTS: Our results showed that gene expression in human white adipose tissue-infiltrated CD11b+ myeloid cells was depot-dependent. The expression of lipid-associated macrophage biomarkers was higher in SAT- than VAT-infiltrated CD11b+ cells (TREM2, CD9, GPNMB, CD68). In contrast, VAT-infiltrated CD11b+ cells overexpressed genes associated with a perivascular M2-like adipose tissue macrophage signature (LYVE1, TIMD4, MRC1). In addition, no classical gene expression polarization (M1 and M2) was shown when VAT and SAT CD11b+ cells were compared. Finally, high levels of CD248, a sensor of lipids associated with insulin resistance, were found to be overexpressed in SAT- compared with VAT-infiltrated CD11b+ myeloid cells.
    CONCLUSIONS: This study characterizes for the first time the macrophage biomarker signature in human VAT- and SAT-infiltrated CD11b+ myeloid cells from individuals with severe obesity. Further studies are required to elucidate their potential role and specific function in the immunometabolism of individuals with obesity.
    DOI:  https://doi.org/10.1002/oby.24323
  4. Diabetes. 2025 Jul 01. pii: db241056. [Epub ahead of print]
    Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice.
    Stephanie K Holm, Valdemar B I Johansen, Pablo Ranea-Robles, Charlotte Svendsen, Christoffer Merrild, Rebecca Rohlfs, Mauro Lo Conte, Wouter F J Hogendorf, Myrte Merkestein, Alexander N Zaykov, Andreas M Fritzen, Bharath K Mani, Christoffer Clemmensen.
       ARTICLE HIGHLIGHTS: Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous ghrelin receptor (GHSR) antagonist and inverse agonist, and represents a novel strategy to modulate the GHSR system for treatment of cardiometabolic disease. A long-acting LEAP2 (LA-LEAP2) analog induces significant weight reduction in rodent models without causing aversion. LA-LEAP2-mediated weight loss is driven by decreased energy intake alongside preservation of energy expenditure during weight loss. Combined LA-LEAP2 and semaglutide therapy supports durable weight loss, addressing a critical gap in obesity treatment.
    DOI:  https://doi.org/10.2337/db24-1056
  5. Diabetes. 2025 Jul 03. pii: db241054. [Epub ahead of print]
    β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes.
    Maria S Svane, Morten Hindsø, Christoffer Martinussen, Carsten Dirksen, Nils B Jørgensen, Nora Hedbäck, Bolette Hartmann, Viggo B Kristiansen, Jens J Holst, Kirstine N Bojsen-Møller, Sten Madsbad.
       ARTICLE HIGHLIGHTS: Roux-en-Y gastric bypass improves glycemic control in patients with type 2 diabetes, but the impact of the improved glycemic control on β-cell sensitivity to glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is sparsely described. GLP-1 and GIP potentiated insulin secretion during clamped hyperglycemia before and after surgery, but, when related to the response to glucose alone, the relative potentiating effects of GIP (on first-phase insulin secretion) and GLP-1 (on first- and second-phase insulin secretion) were reduced postoperatively. The improvement in β-cell function after Roux-en-Y gastric bypass in patients with type 2 diabetes is not driven by improved β-cell sensitivity to incretins but rather other factors, including improved β-cell sensitivity to the changed glucose response and exaggerated postprandial GLP-1.
    DOI:  https://doi.org/10.2337/db24-1054
  6. Cell Signal. 2025 Jun 28. pii: S0898-6568(25)00369-9. [Epub ahead of print]134 111954
    TRIM59 deficiency aggravates HFD-induced obesity in mice associated with increased adipose tissue inflammation, lipid accumulation, and apoptosis.
    Yinni Chen, Xiangnuo Han, Tongzhan Liu, Yuqi Ni, Xinxin Deng, Wenhan Wei, Meixiu Jiang.
      TRIM59 (tripartite motif-containing 59) is involved in many pathological processes including inflammation and tumorigenesis. However, the effect of TRIM59 on obesity remains unknown. In this study, we aimed to investigate the role of TRIM59 in obesity and clarify the involved mechanisms. Our results showed that TRIM59 expression was significantly decreased in fat from high-fat diet (HFD)-induced obese mice. The TRIM59+/- mice with HFD showed increased body weight and white adipose tissue (WAT) weight, larger adipocyte sizes, and increased adipose tissue inflammation with the elevated expression of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 accompanied by an increased macrophage infiltration. Moreover, TRIM59 knockdown increased the serum levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Mechanistically, TRIM59 knockdown is associated with heightened activation of TLR4/JNK-p38/NF-κB signaling pathways to promote inflammation, increase adipogenesis and lipogenesis related genes while decreased lipolysis and β-oxidation related genes expression to increase lipid accumulation, simultaneously increased Bax and caspase 3 while decreased Bcl-2 expression to induce apoptosis, thereby leading to obesity. Taken together, our findings define a new critical biological role of TRIM59 in the regulation of diet-induced obesity through attenuating inflammation, improving lipid metabolism and apoptosis, and we conclude that TRIM59 may provide a novel insight in therapeutic target research for treatment of obesity-associated metabolic diseases.
    Keywords:  Apoptosis; Inflammation; Lipid metabolism; Obesity; TRIM59
    DOI:  https://doi.org/10.1016/j.cellsig.2025.111954
  7. Nutr Rev. 2025 Jun 30. pii: nuaf088. [Epub ahead of print]
    Metabolic Phenotypes, Genotypes, and Gut Microbiome Signatures in Obesity: Implications for Precision Nutrition Strategies in Type 2 Diabetes Prevention.
    Art Muijsenberg, Emanuel E Canfora, Ellen E Blaak.
      The worldwide prevalence of overweight and obesity has increased rapidly in the last decades. This rise has led to a surge in comorbidities such as type 2 diabetes (T2D), cardiometabolic diseases, and mental health issues. While general population-based nutrition guidelines have proven effective in reducing T2D incidence by 50%, a significant 30% of participants do not respond to these interventions. Precision nutrition (PN), tailored towards the metabolic phenotype (metabotype), genotype, or microbial characteristics, has shown promise in improving blood glucose control and cardiometabolic health compared with standard nutritional guidelines. This scoping review aims to discuss advancements in PN over the past decade, focusing on heterogeneity in response to dietary interventions aiming to prevent T2D and related cardiometabolic disease in overweight and obese individuals. A semi-systematic PubMed search with defined criteria was conducted to identify precision nutrition (PN) randomized clinical trials and related post-hoc analyses reporting cardiometabolic health outcomes. Numerous studies have shown actionable diet-host interactions, with intervention stratification based on genotype, gut microbiome, metabolome, lipidome, fasting glucose and insulin, postprandial glycemic response, tissue-specific insulin resistance, or combinations thereof. Many of these metabotypes, genotypes, and microbial signatures allow for accurate cardiometabolic outcome predictions and are actionable targets for future PN research. More recently, machine-learning methodologies in the form of postprandial response prediction models have increasingly been used in PN research. However, prospective evidence on effective PN strategies that may prevent the onset of T2D is currently limited. A mechanistic understanding of response and nonresponse in cardiometabolic outcome improvement is crucial in the development of novel phenotyping methodologies and prediction models in PN. These advancements could lead to more inclusive and effective PN strategies to prevent T2D and related conditions.
    Keywords:  T2D; genotype; glucose metabolism; metabotype; microbiome; obesity; precision nutrition
    DOI:  https://doi.org/10.1093/nutrit/nuaf088
  8. Nat Rev Gastroenterol Hepatol. 2025 Jul 02.
    Intestinal pH: a major driver of human gut microbiota composition and metabolism.
    Julius E Brinck, Anurag K Sinha, Martin F Laursen, Lars O Dragsted, Jeroen Raes, Ruben Vazquez Uribe, Jens Walter, Henrik M Roager, Tine R Licht.
      In the human gastrointestinal tract, pH is a key factor in shaping gut microbial composition and activity, while also being influenced by microbial metabolism. pH varies substantially along the gastrointestinal tract within an individual and between different individuals due to a combination of host, diet, microbial and external factors. The importance of pH on microbiota composition and metabolic response has been widely explored over the past century. Here, we review the literature to explore the major physiological and dietary factors that influence pH along the gastrointestinal tract. From a microbial ecology perspective, we discuss how gastrointestinal pH affects microbiota composition and metabolism. We explore mechanisms by which pH can influence bacterial acid response systems, gene expression and the production of microbial metabolites important for health. Finally, we review the literature regarding the potential role of gastrointestinal pH in human diseases. We propose that we can advance our understanding of the gut microbiota in health and disease by considering gastrointestinal pH. We argue that pH-mediated gut microbial metabolic variation is highly important for predicting and manipulating metabolic output relevant to human health.
    DOI:  https://doi.org/10.1038/s41575-025-01092-6
  9. Diabetologia. 2025 Jun 28.
    Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes.
    Martin J Keller, Aidan J Brady, Jonathan A B Smith, Mladen Savikj, Kirstin MacGregor, Maxence Jollet, Sofia B Öberg, Carolina Nylén, Marie Björnholm, Anette Rickenlund, Marcus Carlsson, Kenneth Caidahl, Anna Krook, Nicolas J Pillon, Juleen R Zierath, Harriet Wallberg-Henriksson.
       AIMS/HYPOTHESIS: The aim of this study was to investigate effects of time of day on glucose management in individuals with type 2 diabetes undertaking high-intensity interval exercise. Additionally, the association between regular eating behaviour and mean amplitude of glycaemic excursions was examined. Specifically, the primary outcome was to determine the effect of the intervention on 24 h glucose levels.
    METHODS: A crossover trial was conducted, comprising 12 men and 12 women with type 2 diabetes and 12 men and 12 women without diabetes. Participants performed high-intensity interval exercise sessions in the morning (09:00 hours) or afternoon (16:00 hours) on separate days at least 7 days apart. Standardised meals were provided the day before exercise, on the day of exercise and on the day after exercise. Continuous glucose monitoring was used to estimate blood glucose levels.
    RESULTS: The 24 h glucose profile did not differ between morning and afternoon exercise across cohorts. However, morning exercise increased blood glucose during the 2 h post-exercise period in men (p<0.05) and women (p<0.01) with type 2 diabetes, but blood glucose was unaltered following afternoon exercise. Glycaemic variability (assessed using the mean amplitude of glycaemic excursions) was reduced during the 3 day meal intervention in men (p<0.001) and women (p<0.05) with type 2 diabetes, but not in individuals without diabetes. Participants exhibited higher morning cortisol levels (p<0.001) compared with afternoon cortisol levels, independently of diagnosis. Individuals with type 2 diabetes exhibited higher levels of the inflammation marker C-reactive protein (p<0.001) and the heart failure marker NT-proBNP (p<0.001) in the morning than in the afternoon.
    CONCLUSIONS/INTERPRETATION: In type 2 diabetes, afternoon high-intensity interval exercise appears to be more effective than morning high-intensity interval exercise for maintaining glucose management. Further research is needed to explore how elevated morning cortisol levels and inflammatory markers influence the exercise response and affect glucose regulation. Additionally, consistent meal timing and controlled energy intake are recommended for reducing the mean amplitude of glycaemic excursions.
    TRIAL REGISTRATION: ClinicalTrials.gov NCT05115682.
    Keywords:  Circadian biology; Continuous glucose monitoring; Diet; High-intensity interval exercise; Inflammation; Sex differences; Type 2 diabetes
    DOI:  https://doi.org/10.1007/s00125-025-06477-5
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