Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration

Julie S. Pedersen (), Marte O. Rygg, Karoline Chrøis, Elahu G. Sustarsic, Zach Gerhart-Hines, Nicolai J. Wever Albrechtsen, Reza R. Serizawa, Viggo B. Kristiansen, Astrid L. Basse, Astrid E. B. Boilesen, Beth H. Olsen, Torben Hansen, Lise Lotte Gluud, Sten Madsbad, Steen Larsen, Flemming Bendtsen and Flemming Dela
Additional contact information
Julie S. Pedersen: Copenhagen University Hospital Hvidovre
Marte O. Rygg: Copenhagen University Hospital Hvidovre
Karoline Chrøis: University of Copenhagen
Elahu G. Sustarsic: University of Copenhagen
Zach Gerhart-Hines: University of Copenhagen
Nicolai J. Wever Albrechtsen: University of Copenhagen
Reza R. Serizawa: Copenhagen University Hospital Hvidovre
Viggo B. Kristiansen: Copenhagen University Hospital Hvidovre
Astrid L. Basse: University of Copenhagen
Astrid E. B. Boilesen: Copenhagen University Hospital Hvidovre
Beth H. Olsen: Copenhagen University Hospital Hvidovre
Torben Hansen: University of Copenhagen
Lise Lotte Gluud: Copenhagen University Hospital Hvidovre
Sten Madsbad: Copenhagen University Hospital Hvidovre
Steen Larsen: University of Copenhagen
Flemming Bendtsen: Copenhagen University Hospital Hvidovre
Flemming Dela: University of Copenhagen

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Impaired mitochondrial oxidative phosphorylation (OXPHOS) in liver tissue has been hypothesised to contribute to the development of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD). It is unknown whether OXPHOS capacities in human visceral (VAT) and subcutaneous adipose tissue (SAT) associate with NAFLD severity and how hepatic OXPHOS responds to improvement in NAFLD. In biopsies sampled from 62 patients with obesity undergoing bariatric surgery and nine control subjects without obesity we demonstrate that OXPHOS is reduced in VAT and SAT while increased in the liver in patients with obesity when compared with control subjects without obesity, but this was independent of NAFLD severity. In repeat liver biopsy sampling in 21 patients with obesity 12 months after bariatric surgery we found increased hepatic OXPHOS capacity and mitochondrial DNA/nuclear DNA content compared with baseline. In this work we show that obesity has an opposing association with mitochondrial respiration in adipose- and liver tissue with no overall association with NAFLD severity, however, bariatric surgery increases hepatic OXPHOS and mitochondrial biogenesis.

Date: 2022
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DOI: 10.1038/s41467-022-30629-5

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