Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease

Susanne Csader; Marsena Jasiel Ismaiah; Tiina Kuningas; Merja Heinäniemi; Janne Suhonen; Ville Männistö; Heikki Pentikäinen; Kai Savonen; Milla-Maria Tauriainen; Jean-Marie Galano; Jetty Chung-Yung Lee; Reeta Rintamäki; Piia Karisola; Hani El-Nezami; Ursula Schwab

doi:10.3390/ijms24108509

Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease

Int J Mol Sci. 2023 May 9;24(10):8509. doi: 10.3390/ijms24108509.

Authors

Susanne Csader¹, Marsena Jasiel Ismaiah², Tiina Kuningas³, Merja Heinäniemi³, Janne Suhonen³, Ville Männistö⁴, Heikki Pentikäinen⁵, Kai Savonen^{5

6}, Milla-Maria Tauriainen^{1

4}, Jean-Marie Galano⁷, Jetty Chung-Yung Lee², Reeta Rintamäki⁸, Piia Karisola⁹, Hani El-Nezami^{1

2}, Ursula Schwab^{1

8}

Affiliations

¹ Department of Public Health and Clinical Nutrition, University of Eastern Finland, FI-70200 Kuopio, Finland.
² School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, China.
³ Institute of Biomedicine, School of Medicine, University of Eastern Finland, FI-70210 Kuopio, Finland.
⁴ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, FI-70210 Kuopio, Finland.
⁵ Kuopio Research Institute of Exercise Medicine, FI-70210 Kuopio, Finland.
⁶ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, FI-70210 Kuopio, Finland.
⁷ Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, F-34093 Montpellier, France.
⁸ Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, FI-70210 Kuopio, Finland.
⁹ Faculty of Medicine, Human Microbiome Research Program, University of Helsinki, FI-00100 Helsinki, Finland.

Abstract

Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG₂), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO₂max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG₂, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F_2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.

Keywords: RNA; adipose tissue; exercise; gene expression; hemoglobin; human; non-alcoholic fatty liver disease; oxylipin.

MeSH terms

Adipose Tissue / metabolism
Female
Gene Expression
High-Intensity Interval Training*
Humans
Liver / metabolism
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / genetics
Non-alcoholic Fatty Liver Disease* / therapy
Weight Loss

Grants and funding

813781/European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie