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

Birgitta W van der Kolk; Maheswary Muniandy; Dorota Kaminska; Marcus Alvarez; Arthur Ko; Zong Miao; Armand Valsesia; Dominique Langin; Maija Vaittinen; Mirva Pääkkönen; Riikka Jokinen; Sanna Kaye; Sini Heinonen; Kirsi A Virtanen; Daniel P Andersson; Ville Männistö; Wim H Saris; Arne Astrup; Mikael Rydén; Ellen E Blaak; Päivi Pajukanta; Jussi Pihlajamäki; Kirsi H Pietiläinen

doi:10.1210/clinem/dgab072

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.

Authors

Birgitta W van der Kolk¹, Maheswary Muniandy¹, Dorota Kaminska², Marcus Alvarez³, Arthur Ko⁴, Zong Miao^{3

5}, Armand Valsesia⁶, Dominique Langin^{7

8}, Maija Vaittinen², Mirva Pääkkönen⁹, Riikka Jokinen¹, Sanna Kaye¹, Sini Heinonen¹, Kirsi A Virtanen^{2

10

11}, Daniel P Andersson¹², Ville Männistö¹³, Wim H Saris¹⁴, Arne Astrup¹⁵, Mikael Rydén¹², Ellen E Blaak¹⁴, Päivi Pajukanta^{3

5

16}, Jussi Pihlajamäki^{2

10}, Kirsi H Pietiläinen^{1

17}

Affiliations

¹ Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland.
² Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
³ Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁴ Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁵ Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA.
⁶ Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland.
⁷ Institut National de la Santé et de la Recherche Médicale (Inserm), Université Paul Sabatier, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
⁸ Department of Biochemistry, Toulouse University Hospitals, France.
⁹ Turku Bioscience Centre, University of Turku and Åbo Akademi University, Finland.
¹⁰ Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland.
¹¹ Turku PET Center, Turku University Hospital, Turku, Finland.
¹² Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
¹³ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
¹⁴ Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, MD Maastricht, The Netherlands.
¹⁵ Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
¹⁶ Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹⁷ Obesity Center, Abdominal center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

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

Abstract

Publication types

MeSH terms

Associated data

Grants and funding