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

• Published in: Nature communications 2022-05, Vol.13 (1), p.2931-2931, Article 2931
• Main Authors: Pedersen, Julie S., Rygg, Marte O., Chrøis, Karoline, Sustarsic, Elahu G., Gerhart-Hines, Zach, Wever Albrechtsen, Nicolai J., Serizawa, Reza R., Kristiansen, Viggo B., Basse, Astrid L., Boilesen, Astrid E. B., Olsen, Beth H., Hansen, Torben, Gluud, Lise Lotte, Madsbad, Sten, Larsen, Steen, Bendtsen, Flemming, Dela, Flemming
• Format: Article
• Language: English
• Subjects: 14; 45/77; 631/443/319/333; 692/4020/4021/1607/2751; 692/699/1702/393; Adipose tissue; Biopsy; Biosynthesis; Body fat; Fatty liver; Gastrointestinal surgery; Humanities and Social Sciences; Liver; Liver diseases; Mitochondrial DNA; multidisciplinary; Obesity; Oxidative phosphorylation; Pathogenesis; Patients; Phosphorylation; Respiration; Science; Science (multidisciplinary); Surgery
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30629-5

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. Impaired mitochondrial function in liver tissue may contribute to the pathogenesis and disease progression of nonalcoholic fatty liver disease (NAFLD). Here the authors report that patients with obesity have lower mitochondrial capacity in adipose tissues but higher capacity in the liver, without overall associations to NAFLD severity, and that bariatric surgery increases hepatic mitochondrial respiration and mitochondrial biogenesis.