Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics

Abstract Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The...

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Autores principales:	Armand Valsesia, Anirikh Chakrabarti, Jörg Hager, Dominique Langin, Wim H. M. Saris, Arne Astrup, Ellen E. Blaak, Nathalie Viguerie, Mojgan Masoodi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b17731f6b55c46028452475f12f8184d
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spelling	oai:doaj.org-article:b17731f6b55c46028452475f12f8184d2021-12-02T17:52:24ZIntegrative phenotyping of glycemic responders upon clinical weight loss using multi-omics10.1038/s41598-020-65936-82045-2322https://doaj.org/article/b17731f6b55c46028452475f12f8184d2020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65936-8https://doaj.org/toc/2045-2322Abstract Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.Armand ValsesiaAnirikh ChakrabartiJörg HagerDominique LanginWim H. M. SarisArne AstrupEllen E. BlaakNathalie ViguerieMojgan MasoodiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Armand Valsesia Anirikh Chakrabarti Jörg Hager Dominique Langin Wim H. M. Saris Arne Astrup Ellen E. Blaak Nathalie Viguerie Mojgan Masoodi Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
description	Abstract Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.
format	article
author	Armand Valsesia Anirikh Chakrabarti Jörg Hager Dominique Langin Wim H. M. Saris Arne Astrup Ellen E. Blaak Nathalie Viguerie Mojgan Masoodi
author_facet	Armand Valsesia Anirikh Chakrabarti Jörg Hager Dominique Langin Wim H. M. Saris Arne Astrup Ellen E. Blaak Nathalie Viguerie Mojgan Masoodi
author_sort	Armand Valsesia
title	Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
title_short	Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
title_full	Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
title_fullStr	Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
title_full_unstemmed	Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
title_sort	integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/b17731f6b55c46028452475f12f8184d
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Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics

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