Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
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Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics. / Valsesia, Armand; Chakrabarti, Anirikh; Hager, Jörg; Langin, Dominique; Saris, Wim H M; Astrup, Arne; Blaak, Ellen E; Viguerie, Nathalie; Masoodi, Mojgan.
In: Scientific Reports, Vol. 10, 9236, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics
AU - Valsesia, Armand
AU - Chakrabarti, Anirikh
AU - Hager, Jörg
AU - Langin, Dominique
AU - Saris, Wim H M
AU - Astrup, Arne
AU - Blaak, Ellen E
AU - Viguerie, Nathalie
AU - Masoodi, Mojgan
N1 - CURIS 2020 NEXS 185
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-020-65936-8
DO - 10.1038/s41598-020-65936-8
M3 - Journal article
C2 - 32514005
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 9236
ER -
ID: 242711396