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

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

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

Kustantaja: Wiley

Julkaisuvuosi: 2026

Lehti: Acta Physiologica

Artikkelin numero: e70150

Vuosikerta: 242

Numero: 2

ISSN: 1748-1708

eISSN: 1748-1716

DOI: https://doi.org/10.1111/apha.70150

Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla

Julkaisukanavan avoimuus : Osittain avoin julkaisukanava

Verkko-osoite: https://doi.org/10.1111/apha.70150

Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/508578541

Rinnakkaistallenteen lisenssi: CC BY

Rinnakkaistallennetun julkaisun versio: Kustantajan versio

Tiivistelmä

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.

Ladattava julkaisu

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Acta Physiologica - 2026 - Kolk - Human Skeletal Muscle Mitochondria Responses to Weight Loss Induced by Bariatric Surgery.pdf

Julkaisussa olevat rahoitustiedot:
The study was supported by the Research Council of Finland (272376, 266286, 314383, 335443, 369181 to Kirsi H. Pietiläinen; 314457 to Anne Juuti; 259926, 265204, 292839, 314456, 335446 to Kirsi A. Virtanen; 361956 and 338417 to Sini Heinonen; 335445, 314455, and Research Council of Finland Profi6 funding (336449) awarded to the University of Oulu: to Eija Pirinen); the Finnish Medical Foundation (Kirsi H. Pietiläinen, Sini Heinonen, Anne Juuti, Eija Pirinen, Kirsi A. Virtanen); the Finnish Diabetes Research Foundation (Birgitta van der Kolk, Sini Heinonen, Kirsi H. Pietiläinen, Kirsi A. Virtanen); the Orion Foundation Sr (Birgitta van der Kolk, Sini Heinonen); the Novo Nordisk Foundation (NNF10OC1013354, NNF17OC0027232, NNF20OC0060547, NNF24OC0091683 and NNF25SA0103783 to Kirsi H. Pietiläinen; NNF24SA0090438 to Birgitta van der Kolk; NNF23SA0083953 and NNF25OC0100827 to Sini Heinonen); the Paulo Foundation (Sini Heinonen, Kirsi H. Pietiläinen); the Gyllenberg Foundation (Kirsi H. Pietiläinen); the Finnish Foundation for Cardiovascular Research (Kirsi H. Pietiläinen); the Sigrid Juselius Foundation (Kirsi H. Pietiläinen, Kirsi A. Virtanen); the Paavo Nurmi Foundation (Sini Heinonen); Helsinki University Hospital Research Funds (Sini Heinonen, Kirsi H. Pietiläinen, and Anne Juuti); Government Research Funds (Kirsi H. Pietiläinen, Sini Heinonen, Kirsi A. Virtanen); and the University of Helsinki (Kirsi H. Pietiläinen).