Human Skeletal Muscle Mitochondria Responses to Weight Loss Induced by Bariatric Surgery or Lifestyle Intervention

Birgitta W van der Kolk; Sini Heinonen; James W White; Anita Wagner; Jari E Karppinen; Sina Saari; Maheswary Muniandy; Simo Metsikkö; Eugène T Dillon; Per-Henrik Groop; Tuure Saarinen; Carel W Le Roux; Kirsi A Virtanen; Neil G Docherty; Eija Pirinen; Anne Juuti; Kirsi H Pietiläinen

doi:10.1111/apha.70150

Human Skeletal Muscle Mitochondria Responses to Weight Loss Induced by Bariatric Surgery or Lifestyle Intervention

Acta Physiol (Oxf). 2026 Feb;242(2):e70150. doi: 10.1111/apha.70150.

Authors

Birgitta W van der Kolk¹, Sini Heinonen^{1

2}, James W White^{3

4}, Anita Wagner^{1

5}, Jari E Karppinen¹, Sina Saari¹, Maheswary Muniandy¹, Simo Metsikkö¹, Eugène T Dillon⁶, Per-Henrik Groop^{1

7

8

9

10}, Tuure Saarinen¹¹, Carel W Le Roux³, Kirsi A Virtanen^{12

13}, Neil G Docherty³, Eija Pirinen^{1

14

15

16}, Anne Juuti³, Kirsi H Pietiläinen^{1

17}

Affiliations

¹ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
² Department of Internal Medicine and Rehabilitation, Helsinki University Hospital, Helsinki, Finland.
³ Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
⁴ Department of Biomedical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK.
⁵ Chair for Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan, Freising, Germany.
⁶ Mass Spectrometry Resource, Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
⁷ Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
⁸ Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁹ Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹⁰ Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia.
¹¹ Department of Gastrointestinal Surgery, Abdominal Center, HUS and University of Helsinki, Helsinki, Finland.
¹² Turku PET Centre, Turku University Hospital, Turku, Finland.
¹³ Turku PET Centre, University of Turku, Turku, Finland.
¹⁴ Faculty of Medicine, Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland.
¹⁵ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
¹⁷ Healthy Weight Hub, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.

Abstract

Aim: We investigated how weight loss induced by bariatric surgery or lifestyle intervention affects skeletal muscle mitochondrial metabolism.

Methods: We studied two weight-loss cohorts: RYSA (BMI ≥ 35 kg/m²; n = 39, including 18 with diabetes) undergoing bariatric surgery, and CRYO (BMI ≥ 30 kg/m²; n = 19) undergoing a lifestyle intervention with a low-calorie diet. Assessments were performed at 5-6 and 12 months and included muscle proteome (LC-MS/MS), mitochondrial biogenesis by mtDNA amount (qPCR), number and morphology (transmission electron microscopy) in both cohorts, and mitochondrial oxidative capacity (high-resolution respirometry) in the surgery cohort.

Results: Both cohorts achieved clinically meaningful weight loss, greater following surgery (24.4% vs 9.0% at 12 months). Per 1% weight loss, bariatric surgery was associated with significant downregulation of glycolysis pathways at 12 months. OXPHOS complex subunit proteins were associated with upregulation in individuals without diabetes but downregulation in those with diabetes. Lifestyle intervention was associated with downregulated OXPHOS complex subunits at 5 months. Mitochondrial morphology remained unchanged, while mtDNA amount correlated negatively with weight loss percentage in both cohorts. In the surgery cohort, complex I and complex I + II-mediated respiration increased 3.2- and 2.9-fold at 12 months, reflecting improved oxidative capacity.

Conclusion: Bariatric surgery was associated with increased skeletal muscle mitochondrial respiration despite unchanged morphology and reduced mtDNA amount, whereas lifestyle-induced weight loss showed a transient downregulation of OXPHOS-related proteins with other mitochondrial markers remaining stable. Surgery-induced weight loss may reflect improved mitochondrial efficiency in skeletal muscle, potentially influenced by diabetes status. Long-term functional mitochondrial adaptations after weight loss require future studies.

Trial registration: RYSA: ClinicalTrials.gov ID NCT02882685; CRYO: ClinicalTrials.gov ID NCT01312090.

Keywords: bariatric surgery; lifestyle intervention; mitochondria; skeletal muscle; type 2 diabetes; weight loss.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Adult
Bariatric Surgery*
Female
Humans
Life Style*
Male
Middle Aged
Mitochondria, Muscle* / metabolism
Muscle, Skeletal* / metabolism
Obesity / metabolism
Obesity / surgery
Weight Loss* / physiology

Associated data

ClinicalTrials.gov/NCT01312090
ClinicalTrials.gov/NCT02882685

Abstract

Publication types

MeSH terms

Associated data

Grants and funding