Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr−/−.Leiden mice

Anouk C. Tengeler, Eveline Gart, Maximilian Wiesmann, Ilse A.C. Arnoldussen, Wim van Duyvenvoorde, Marloes Hoogstad, Pieter J. Dederen, Vivienne Verweij, Bram Geenen, Tamas Kozicz, Robert Kleemann, Martine C. Morrison, Amanda J. Kiliaan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr−/−.Leiden mice. Ldlr−/−.Leiden mice received 16 weeks either a high-fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD-fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD-control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD-induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1-positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD-induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD-induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.

Original languageEnglish
Pages (from-to)9575-9593
JournalFASEB Journal
Volume34
Issue number7
Early online date30 May 2020
DOIs
Publication statusPublished - Jul 2020

Keywords

  • cerebral vasoreactivity
  • cognition
  • liver fibrosis
  • neuroimaging
  • obesity

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    Tengeler, A. C., Gart, E., Wiesmann, M., Arnoldussen, I. A. C., van Duyvenvoorde, W., Hoogstad, M., Dederen, P. J., Verweij, V., Geenen, B., Kozicz, T., Kleemann, R., Morrison, M. C., & Kiliaan, A. J. (2020). Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr−/−.Leiden mice. FASEB Journal, 34(7), 9575-9593. https://doi.org/10.1096/fj.202000455R