Metabolic profiling of tissue-specific insulin resistance in human obesity: results from the Diogenes study and the Maastricht Study.

Adult Female Humans Insulin Resistance Ketone Bodies / blood Liver / metabolism Male Metabolomics Middle Aged Multicenter Studies as Topic Muscle, Skeletal / metabolism Obesity / metabolism Observational Studies as Topic Overweight / metabolism Prospective Studies Randomized Controlled Trials as Topic

Journal

International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108

Informations de publication

Date de publication:
06 2020
Historique:
received: 27 06 2019
accepted: 04 03 2020
revised: 25 02 2020
pubmed: 24 3 2020
medline: 30 10 2021
entrez: 24 3 2020
Statut: ppublish

Résumé

Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles. This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m Both HIRI and MISI were associated with higher levels of valine, isoleucine, oxo-isovaleric acid, alanine, lactate, and triglycerides, and lower levels of glycine (all p < 0.05). HIRI was also associated with higher levels of leucine, hydroxyisobutyrate, tyrosine, proline, creatine, and n-acetyl and lower levels of acetoacetate and 3-OH-butyrate (all p < 0.05). Except for valine, these results were replicated for all available metabolites in the Maastricht Study. In persons with obesity without diabetes, both liver and muscle IR show a circulating metabolic profile of elevated (branched-chain) amino acids, lactate, and triglycerides, and lower glycine levels, but only liver IR associates with lower ketone body levels and elevated ketogenic amino acids in circulation, suggestive of decreased ketogenesis. This knowledge might enhance developments of more targeted tissue-specific interventions to prevent progression to more severe disease stages.

Sections du résumé

BACKGROUND
Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles.
METHODS
This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m
RESULTS
Both HIRI and MISI were associated with higher levels of valine, isoleucine, oxo-isovaleric acid, alanine, lactate, and triglycerides, and lower levels of glycine (all p < 0.05). HIRI was also associated with higher levels of leucine, hydroxyisobutyrate, tyrosine, proline, creatine, and n-acetyl and lower levels of acetoacetate and 3-OH-butyrate (all p < 0.05). Except for valine, these results were replicated for all available metabolites in the Maastricht Study.
CONCLUSIONS
In persons with obesity without diabetes, both liver and muscle IR show a circulating metabolic profile of elevated (branched-chain) amino acids, lactate, and triglycerides, and lower glycine levels, but only liver IR associates with lower ketone body levels and elevated ketogenic amino acids in circulation, suggestive of decreased ketogenesis. This knowledge might enhance developments of more targeted tissue-specific interventions to prevent progression to more severe disease stages.

Identifiants

DOI: 10.1038/s41366-020-0565-z PMID: 32203114
pubmed: 32203114
doi: 10.1038/s41366-020-0565-z
pii: 10.1038/s41366-020-0565-z
doi:

Substances chimiques

Ketone Bodies 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1376-1386

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Auteurs

Nicole Vogelzangs (N)

Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. n.vogelzangs@maastrichtuniversity.nl.
Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands. n.vogelzangs@maastrichtuniversity.nl.
CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands. n.vogelzangs@maastrichtuniversity.nl.
ORCID: 0000-0002-9109-2961

Carla J H van der Kallen (CJH)

CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.
ORCID: 0000-0003-1468-8793

Marleen M J van Greevenbroek (MMJ)

CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.

Birgitta W van der Kolk (BW)

Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
ORCID: 0000-0001-8608-541X

Johan W E Jocken (JWE)

Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Gijs H Goossens (GH)

Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Nicolaas C Schaper (NC)

CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.

Ronald M A Henry (RMA)

CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.

Simone J P M Eussen (SJPM)

Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
CAPHRI School for Care and Public Health Research, Maastricht University, Maastricht, The Netherlands.

Armand Valsesia (A)

Nestlé Institute of Health Sciences, Lausanne, Switzerland.

Thomas Hankemeier (T)

Netherlands Metabolomics Centre, Leiden, The Netherlands.

Arne Astrup (A)

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
ORCID: 0000-0001-8968-8996

Wim H M Saris (WHM)

Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
ORCID: 0000-0003-0985-0047

Coen D A Stehouwer (CDA)

CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.

Ellen E Blaak (EE)

Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
ORCID: 0000-0002-2496-3464

Ilja C W Arts (ICW)

Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.
Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands.
CARIM School for Cardiovascular Diseases, Maastricht University & Maastricht University Medical Centre, Maastricht, The Netherlands.
ORCID: 0000-0001-6462-6692

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