Effects of reducing sedentary behavior on liver insulin sensitivity, liver fat content, and liver enzyme levels: a six-month randomized controlled trial

  • Saara Laine*
  • , Tanja Sjöros
  • , Taru Garthwaite
  • , Miikka Juhani Honka
  • , Eliisa Löyttyniemi
  • , Jooa Norha
  • , Olli Eskola
  • , Mikko Koivumäki
  • , Henri Vähä-Ypyä
  • , Harri Sievänen
  • , Tommi Vasankari
  • , Jussi Hirvonen
  • , Kirsi Laitinen
  • , Noora Houttu
  • , Kari K. Kalliokoski
  • , Virva Saunavaara
  • , Juhani Knuuti
  • , Ilkka H.A. Heinonen
  • *Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

Metabolic syndrome increases the risk of developing noncommunicable diseases such as metabolic dysfunction-associated steatotic liver disease. The aim was to investigate the effects of sedentary behavior (SB) reduction on liver glucose uptake (LGU), endogenous glucose production (EGP), liver fat content (LFC), and liver enzyme levels [alanine aminotransferase (ALT), aspartate aminotransferase, and c-glutamyltransferase]. Forty-four sedentary (daily SB time ≥ 10 h), physically inactive middle-aged adults with metabolic syndrome were randomized into intervention (INT; n = 23, 21 completed) and control (CON; n = 21, 19 completed) groups. For 6 mo, INT aimed to limit SB by 1 h/day, whereas CON aimed to maintain usual habits. SB and physical activity (PA) were measured continuously with hip-worn accelerometers. Before and at the end of the intervention, LGU was measured using positron emission tomography during the hyperinsulinemic-euglycemic clamp. EGP was calculated, and LFC was measured by magnetic resonance spectroscopy. INT reduced SB by 51 [95% confidence interval (CI): 22, 78] min/day and increased moderate-to-vigorous physical activity (MVPA) by 22 (95% CI: 12, 33) min/day, with no significant change in CON. Differences in liver health markers between the groups were not significant. However, according to the exploratory analyses among participants who successfully reduced SB, ALT decreased (-1.1 [95% CI: 0.93, 1.36] U/L) compared with the continuously sedentary participants (+ 0.8 [95% CI: 0.65, 1.05] U/L) (group X time, P = 0.006). To enhance liver health, reducing SB for longer durations and/or increasing the intensity of PA may be necessary. However, successfully reducing SB may lead to better levels of circulating ALT liver enzymes.

Original languageEnglish
Pages (from-to)E756-E771
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume328
Issue number6
DOIs
Publication statusPublished - Jun 2025
MoE publication typeA1 Journal article-refereed

Funding

This study was conducted within the Centre of Excellence in Cardiovascular and Metabolic Research, supported by the Research Council of Finland, the University of Turku, Turku University Hospital, and Åbo Akademi University. We extend our gratitude to the personnel of Turku PET Centre, the University of Turku, and the Turku University Hospital Laboratory for the exceptional technical support. The study was financially supported by the Research Council of Finland Grant 324243 (to I.H.A.H.); Instrumentarium Science Foundation Grant 200034; Turku University Foundation Grant 80519; Juho Vainio Foundation Grants 202100392 and 202300322; Hospital District of South-West Finland Grant 11212; and Yrjö Jahnsson Foundation Grant 20227535 (to S.L.); the Jalmari and Rauha Ahokas Foundation; the Finnish Cultural Foundation’s Varsinais-Suomi Regional Fund Grant 85232102; and State Research Funding from Turku University Hospital (to M.-J.H.). The study was financially supported by the Research Council of Finland Grant 324243 (to I.H.A.H.); Instrumentarium Science Foundation Grant 200034; Turku University Foundation Grant 80519; Juho Vainio Foundation Grants 202100392 and 202300322; Hospital District of South-West Finland Grant 11212; and Yrjo€ Jahnsson Foundation Grant 20227535 (to S.L.); the Jalmari and Rauha Ahokas Foundation; the Finnish Cultural Foundation’s Varsinais-Suomi Regional Fund Grant 85232102; and State Research Funding from Turku University Hospital (to M.-J.H.).

Keywords

  • endogenous glucose production
  • liver fat
  • liver glucose uptake
  • physical activity
  • sedentary behavior

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