Differential Mitochondrial Gene Expression in Adipose Tissue Following Weight Loss Induced by Diet or Bariatric Surgery

B.W. van der Kolk*, M. Muniandy, D. Kaminska, M. Alvarez, A. Ko*, Z. Miao, A. Valsesia, D. Langin, M. Vaittinen, M. Paakkonen, R. Jokinen, S. Kaye, S. Heinonen, K.A. Virtanen, D.P. Andersson, V. Mannisto, W.H. Saris, A. Astrup, M. Ryden, E.E. BlaakP. Pajukanta, J. Pihlajamaki, K.H. Pietilainen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.

Objective: To investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in 4 independent weight-loss studies.

Methods: The 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.

Results: Diet-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).

Conclusions: Differentially 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.

Original languageEnglish
Pages (from-to)1312-1324
Number of pages13
JournalJournal of Clinical Endocrinology & Metabolism
Volume106
Issue number5
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • BIOGENESIS
  • FAT
  • MAINTENANCE
  • MECHANISMS LINKING OBESITY
  • OVERWEIGHT
  • Y GASTRIC BYPASS
  • adipose tissue
  • bariatric surgery
  • diet-induced
  • mitochondria
  • transcriptomics
  • weight loss
  • LIFE-STYLE
  • INTERVENTION

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