Isocaloric switch from low-fat to Western high-fat diet triggers transcriptomic reprogramming and ectopic olfactory receptor responses.

Jonathan Bertram, Michail Lazaratos, Michael Kruse, Silke Hornemann, Alexander S Mosig, Turid Frahnow, Martin Osterhoff, Andreas Busjahn, Anne-Cathrin Ost, Annette Schürmann, Olga Pivovarova-Ramich, Andreas Fh Pfeiffer

Journal: Science advances 2026;12(34):eaef5698

PMID: 42616886

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Abstract

Although Western diet (WD) rich in saturated fat is regarded as a trigger of metabolic disease and inflammation, the role of this diet in the absence of obesity is unclear. We studied the metabolic, inflammatory, anthropometric, and adipose tissue transcriptomic responses of 92 twins to 6 weeks of WD following 6 weeks of a healthy low-fat diet while maintaining stable body weight. The WD increased total, LDL and HDL cholesterol but not triglycerides or free fatty acids and induced transient and moderate increases of insulin resistance and some inflammatory markers after 1 week, which disappeared after 6 weeks. Extensive transcriptomic changes reflected restructuring of subcutaneous abdominal adipose tissue. Olfactory receptor (OR) mRNAs were increased in correlation with insulin resistance, liver, and visceral fat, cytokines like IL-18 and VEGF, but inversely related to adiponectin and extracellular NAMPT. In conclusion, WD triggers metabolic and transcriptomic reprogramming closely linked to ectopic OR responses.

Address: Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolism, Berlin, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Institute of Biochemistry II, Jena University Hospital, Jena, Germany.; Department of Molecular Metabolism and Precision Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; HealthTwiSt GmbH, Berlin, Germany.; Department of Molecular Metabolism and Precision Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Institute of Midwifery Science and Interprofessional Perinatal Medicine, Leipzig University, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany.; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolism, Berlin, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Department of Molecular Metabolism and Precision Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Endocrinology and Metabolism, Berlin, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.

DOI: 10.1126/sciadv.aef5698

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MeSH Terms: Humans, Diet, High-Fat, Transcriptome, Receptors, Odorant, Insulin Resistance, Female, Diet, Fat-Restricted, Male, Adipose Tissue, Gene Expression Regulation, Gene Expression Profiling