Metabolic Phenotyping

Group Head: Jörg Hager, Ph.D. Contact

Metabolic flexibility describes the concept of how the body responds to external challenges (e.g. changes in food intake, temperature etc.) in order to keep the metabolism balanced. Individuals that are less metabolically flexible, i.e less capable to adjust to changes in the environment are more prone to metabolic diseases, especially obesity and its related co-morbidities type 2 diabetes mellitus and cardiovascular disease.

The aim of our research is to understand the molecular mechanisms that underlie differences in metabolic flexibility in respect to the genetic make-up of individuals and how they’re influenced by nutrition. We do this by starting from clinical intervention trials that test the metabolic flexibility in humans. Our key clinical readouts are the capacity to loose or maintain weight and glycemic (i.e. blood sugar) control. The overall goal is to propose new and more personalized solutions to regain and/or improve metabolic health.

Key Goals

  • Identify the molecular mechanisms that underlie the differences in the capacity to maintain weight in obese individuals, their relation to glucose control and how macro- and micro-nutrient composition influences these mechanisms and clinical outcomes. This research will lead to biomarkers that can be used to predict efficacy of a particular intervention for a person and potentially new targets for intervention.
  • Understand the mechanisms that lead to resistance to weight gain in humans. We do this by studying a particular human phenotype called Constitutional Thinness (CT). CT individuals are characterized by low body weight and the resistance to gain weight when challenged by a high caloric diet. We aim to understand the molecular mechanisms responsible for this phenotype in order to identify new targets for intervention in obesity.
  • Identify early (childhood) biomarkers that predict glycemic control (hyperglycemia, type 2 diabetes) in adulthood. This may allow new and earlier (nutritional-) interventions to avoid or delay the onset of type 2 diabetes.
  • Explore the influence of different food compositions (e.g. vegan vs. animal protein based) on molecular markers of metabolic flexibility. Understand the individual differences in the response of these diets.

Meet Dr Jörg Hager


Key Publications of the Group*

Valsesia A, Saris WH, Astrup A, Hager J, Masoodi M. Distinct lipid profiles predict improved glycemic control in obese, non-diabetic patients after a low-caloric diet intervention: the Diet, Obesity and Genes randomized trial. Am J Clin Nutr. 2016 Aug 10. See news release

Matone A, Scott-Boyer MP, Carayol J, Fazelzadeh P, Lefebvre G, Valsesia A, Charon C, Vervoort J, Astrup A, Saris WH, Morine M, Hager J. Network analysis of metabolite GWAS hits: Implication of CPS1 and the urea cycle in weight maintenance. PLoS One, 2016 Mar 3;11(3).

Brahe LK, Angquist L, Larsen LH, Vimaleswaran KS, Hager J, Viguerie N, Loos RJ, Handjieva-Darlenska T, Jebb SA, Hlavaty P, Larsen TM, Martinez JA, Papadaki A, Pfeiffer AF, van Baak MA, Sørensen TI, Holst C, Langin D, Astrup A, Saris WH. Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids: the DiOGenes study. Br J Nutr. 2013 Sep;110(5):790-6.

Stocks T, Angquist L, Hager J, Charon C, Holst C, Martinez JA, Saris WH, Astrup A, Sørensen TI, Larsen LH. TFAP2B -Dietary Protein and Glycemic Index Interactions and Weight Maintenance after Weight Loss in the DiOGenes Trial. Hum Hered. 2013;75(2-4):213-9. doi: 10.1159/000353591. Epub 2013 Sep27.

*Some of these publications were done before the scientist/s joined the Nestlé Institute of Health Sciences