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; Flemming Dela

doi:10.1038/s41467-022-30629-5

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

Julie S. Pedersen (Corresponding Author), 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, Flemming Dela

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20 Citations (Scopus)

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.

Original language	English
Article number	2931
Number of pages	15
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30629-5
Publication status	Published - Dec 2022
Externally published	Yes

Field of Science*

1.4 Chemical sciences
3.1 Basic medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-30629-5Licence: CC BY

Influence of NAFLD and bariatric surgeryFinal published version, 1.18 MBLicence: CC BY

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Pedersen, J. S., Rygg, M. O., Chrøis, K., Sustarsic, E. G., Gerhart-Hines, Z., Wever Albrechtsen, N. J., Serizawa, R. R., Kristiansen, V. B., Basse, A. L., Boilesen, A. E. B., Olsen, B. H., Hansen, T., Gluud, L. L., Madsbad, S., Larsen, S., Bendtsen, F., & Dela, F. (2022). Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration. Nature Communications, 13(1), Article 2931. https://doi.org/10.1038/s41467-022-30629-5

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title = "Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration",

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.",

author = "Pedersen, {Julie S.} and Rygg, {Marte O.} and Karoline Chr{\o}is and Sustarsic, {Elahu G.} and Zach Gerhart-Hines and {Wever Albrechtsen}, {Nicolai J.} and Serizawa, {Reza R.} and Kristiansen, {Viggo B.} and Basse, {Astrid L.} and Boilesen, {Astrid E.B.} and Olsen, {Beth H.} and Torben Hansen and Gluud, {Lise Lotte} and Sten Madsbad and Steen Larsen and Flemming Bendtsen and Flemming Dela",

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year = "2022",

month = dec,

doi = "10.1038/s41467-022-30629-5",

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Pedersen, JS, Rygg, MO, Chrøis, K, Sustarsic, EG, Gerhart-Hines, Z, Wever Albrechtsen, NJ, Serizawa, RR, Kristiansen, VB, Basse, AL, Boilesen, AEB, Olsen, BH, Hansen, T, Gluud, LL, Madsbad, S, Larsen, S, Bendtsen, F & Dela, F 2022, 'Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration', Nature Communications, vol. 13, no. 1, 2931. https://doi.org/10.1038/s41467-022-30629-5

TY - JOUR

T1 - Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration

AU - Pedersen, Julie S.

AU - Rygg, Marte O.

AU - Chrøis, Karoline

AU - Sustarsic, Elahu G.

AU - Gerhart-Hines, Zach

AU - Wever Albrechtsen, Nicolai J.

AU - Serizawa, Reza R.

AU - Kristiansen, Viggo B.

AU - Basse, Astrid L.

AU - Boilesen, Astrid E.B.

AU - Olsen, Beth H.

AU - Hansen, Torben

AU - Gluud, Lise Lotte

AU - Madsbad, Sten

AU - Larsen, Steen

AU - Bendtsen, Flemming

AU - Dela, Flemming

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2931

ER -

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

Abstract

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