Journal Article

Intercellular adhesion molecule-1 protects against adipose tissue inflammation and insulin resistance but promotes liver disease activity in western-diet fed mice

Hamm, Sabine, Kiessling, Fabian, Schraven, Sarah, Dreschers, Stephan, Gebert, Laura, Wagner, Norbert, Clavel, Thomas, Eswaran, Sreepradha, Schippers, Angela, Treichel, Nicole, Ritz, Thomas, Seeger, Agnes

2025

Overview

Metabolic dysfunction associated steatotic liver disease (MASLD) presents a growing global health problem. Disease progression is promoted not only by hepatic leukocyte accumulation but also by inflammatory signals from adipose tissue and an altered gut microbiome. To determine the contribution of intercellular adhesion molecule-1 (ICAM-1) to MASLD pathogenesis, male mice with an ICAM-1 mutation (Icam1 tmBay ) and wild type (WT) mice were compared in 12 and 24-week feeding experiments with a Western-style diet (WD) containing 40 kcal% fat, 20 kcal% fructose, and 2% cholesterol. WD-induced MASLD was accompanied by increased ICAM-1 expression in liver, epididymal white adipose tissue (EWAT), and intestine in WT mice. WD-fed Icam1 tmBay mice exhibited increased circulating neutrophils, higher frequencies of inflammatory leukocytes in EWAT, and a worsened glucose tolerance when compared to WT mice. In contrast, the mutation resulted in reduced WD-induced liver disease activity and less accumulation of intrahepatic leukocytes. WD-feeding caused substantial changes in fecal microbiota with decreased microbial diversity that differed between the mouse strains. In conclusion, ICAM-1 positively regulates adipose tissue homeostasis and protects from insulin resistance but promotes liver damage in diet-induced obesity. This points to organ-specific roles for ICAM-1 and the potential of liver-specific targeting of ICAM-1 for treatment of MASLD.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250 / 631/250/256 / 692/4020/4021/1607/2750 / 692/4020/4021/1607/2751 / Abdomen / Adhesion / Adipose tissue / Adipose Tissue - metabolism / Adipose Tissue - pathology / Adipose Tissue, White - metabolism / Adipose Tissue, White - pathology / Animals / Antigens / Body composition / Body fat / Carbohydrates / Cell adhesion / Cell adhesion & migration / Cholesterol / Cytokines / Diet / Diet, Western - adverse effects / Disease progression / Disease resistance / Endothelium / Enzymes / Fatty Liver - etiology / Fatty Liver - metabolism / Fatty Liver - pathology / Fecal microflora / Gastrointestinal Microbiome / Genotype & phenotype / Global health / Glucose / Glucose tolerance / Homeostasis / Humanities and Social Sciences / ICAM-1 / Inflammation / Inflammation - metabolism / Inflammation - pathology / Insulin Resistance / Intercellular adhesion molecule 1 / Intercellular Adhesion Molecule-1 - genetics / Intercellular Adhesion Molecule-1 - metabolism / Intestinal microflora / Leukocytes / Leukocytes (neutrophilic) / Liver / Liver - metabolism / Liver - pathology / Liver diseases / Male / MASLD / Metabolic syndrome / Metabolism / Mice / Mice, Inbred C57BL / Microbiome / Microbiomes / Microbiota / multidisciplinary / Mutation / Neutrophils / Proteins / Public health / Science / Science (multidisciplinary) / Small intestine / Statistical significance / Steatohepatitis / Western diet