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

J Clin Endocrinol Metab. 2021 Apr 23;106(5):1312-1324. doi: 10.1210/clinem/dgab072.

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.

Trial registration: ClinicalTrials.gov NCT00390637 NCT01312090 NCT01785134.

Keywords: adipose tissue; bariatric surgery; diet-induced; mitochondria; transcriptomics; weight loss.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Adult
  • Bariatric Surgery
  • Diet, Reducing
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Genes, Mitochondrial / genetics*
  • Humans
  • Male
  • Metabolic Networks and Pathways / genetics
  • Middle Aged
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Obesity, Morbid / diet therapy
  • Obesity, Morbid / genetics
  • Obesity, Morbid / surgery
  • Retrospective Studies
  • Weight Loss / genetics
  • Weight Loss / physiology*
  • Weight Reduction Programs

Associated data

  • ClinicalTrials.gov/NCT00390637
  • ClinicalTrials.gov/NCT01312090
  • ClinicalTrials.gov/NCT01785134