Abstract
ContextMitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.ObjectiveTo investigate how SAT mitochondria change following diet-induced and bariatric surgery–induced weight-loss interventions in 4 independent weight-loss studies.MethodsThe DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up.ResultsDiet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: −8.7 following LCD, −4.4 following weight maintenance; CRYO: IPA z-score: −5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001).ConclusionsDifferentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.
Highlights
Weight loss effectively reduces health risks among people who are overweight or with obesity
Differential RNA expression analyses The DiOGenes dietary intervention and the Kuopio OBesity Surgery (KOBS) bariatric surgery intervention were used as the discovery material, while we used the CRYO and DEOSH cohorts as the diet- and surgery-induced replication datasets, respectively
The DiOGenes dietary intervention and the KOBS bariatric surgery intervention were used as the discovery material, while we used the CRYO and DEOSH cohorts, respectively, as diet- and surgery-induced replication datasets
Summary
Weight loss effectively reduces health risks among people who are overweight or with obesity. An increased SAT mitochondrial capacity was observed following surgically induced weight loss (1618), indicating that bariatric surgery may cause a metabolically more advantageous change to the SAT mitochondrial function than dieting. This implies that SAT mitochondrial activity could impact the mechanism explaining more successful weight maintenance following different intervention types, while the true long-term effects are unclear. We report analyses from 172 participants (34% with T2DM) who underwent Roux-en-Y gastric bypass (RYGB) surgery and for whom abdominal SAT RNA sequencing data were available at baseline and at 12 months follow-up. Weight and metabolic health were assessed at baseline and 12 months
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