Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice

Arnoldussen, I A C; Wiesmann, M; Pelgrim, C E; Wielemaker, E M; van Duyvenvoorde, W; Amaral-Santos, P L; Verschuren, L; Keijser, B J F; Heerschap, A; Kleemann, R; Wielinga, P Y; Kiliaan, A J

doi:10.1038/ijo.2017.52

Cited by 101Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesFatty Acid Research and Health

Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice

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Arnoldussen, I A C, Wiesmann, M, Pelgrim, C E, Wielemaker, E M, van Duyvenvoorde, W, Amaral-Santos, P L, Verschuren, L, Keijser, B J F +4 more·2017·International Journal of Obesity

DOI 10.1038/ijo.2017.52

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Abstract

Objective Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing body weight and adiposity. Subjects We examined the impact of a high-fat diet (HFD) followed by intervention with 5% (w/w) dietary butyrate, on metabolism, microbiota, brain function and structure in the low-density-lipoprotein receptor knockout (LDLr-/-) mouse model in mid and late life. Results In mid-adult mice, 15 weeks of HFD-induced adiposity, liver fibrosis and neuroinflammation, increased systolic blood pressure and decreased cerebral blood flow, functional connectivity assessed with neuroimaging. The subsequent 2 months butyrate intervention restored these detrimental effects to chow-fed control levels. Both HFD and butyrate intervention decreased variance in fecal microbiota composition. In late-adult mice, HFD showed similar detrimental effects and decreased cerebral white and gray matter integrity, whereas butyrate intervention attenuated only metabolic parameters. Conclusion HFD induces detrimental effects in mid- and late-adult mice, which can be attenuated by butyrate intervention. These findings are consistent with reported associations between midlife obesity and cognitive impairment and dementia in humans. We suggest that butyrate may have potential in prevention and treatment of midlife obesity.

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9-month old, but not 12-month old, diet-induced obese low-density-lipoprotein receptor transgenic mice have decreased hippocampal cerebral blood flow and functional connectivity, spatial memory, and increased hippocampal microglia activation, all of which were rescued by butyrate supplementation.
“In addition, 9-month old, but not 12-month old diet-induced obese, low-density-lipoprotein receptor transgenic mice have decreased hippocampal cerebral blood flow and functional connectivity, spatial memory, and increased hippocampal microglia activation, all of which were rescued by butyrate supplementation (Arnoldussen et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Arnoldussen et al., 2017
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The hippocampus and striatum seem to be affected by gut-derived SCFAs, indicating that SCFAs may play a modulatory role in learning and cognition as well as reward-associated behaviors.
“In addition, particularly the hippocampus and striatum seem to be affected by gut-derived SCFAs, indicating that SCFAs may play a modulatory role in learning and cognition (Arnoldussen et al., 2017;Val-Laillet et al., 2018), as well as reward-associated behaviors (Byrne et al., 2016;van de Wouw et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Arnoldussen et al., 2017
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Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial
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In vivo imaging biomarkers of neuroinflammation in the development and assessment of stroke therapies - towards clinical translation
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The Microbiota-Gut Axis in Premature Infants: Physio-Pathological Implications
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Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice
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A casein hydrolysate based formulation attenuates obesity and associated non-alcoholic fatty liver disease and atherosclerosis in LDLr-/-.Leiden mice
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Blood-brain barrier pathology in cerebral small vessel disease
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Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice
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Predictive microbial feature analysis in patients with depression after acute ischemic stroke
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Resistance exercise improves learning and memory and modulates hippocampal metabolomic profile in aged rats
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Butyric Acid Precursor Tributyrin Modulates Hippocampal Synaptic Plasticity and Prevents Spatial Memory Deficits: Role of PPARγ and AMPK
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Determining the emotional regulation function of Bifidobacterium breve : the role of gut metabolite regulation over colonization capability
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Butyrate improves testicular spermatogenic dysfunction induced by a high-fat diet
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Severe Cognitive Decline in Long-term Care Is Related to Gut Microbiome Production of Metabolites Involved in Neurotransmission, Immunomodulation, and Autophagy
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Butyric acid reduced lipid deposition in immortalized chicken preadipocyte by inhibiting cell proliferation and differentiation
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Rosuvastatin ameliorates obesity-associated insulin resistance in high-fat diet-fed mice by modulating the gut microbiota and gut metabolites
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Malícia honey (Mimosa quadrivalvis L.) produced by the jandaíra bee (Melipona subnitida D.) improves anxious-like behaviour and has anti-adiposity effect in cafeteria diet-induced obese rats
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Partial removal of visceral epididymal white adipose tissue in obese Ldlr-/-.Leiden mice impacts adipokine secretion, plasma free fatty acids, and improves cerebrovascular health
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Authors: Arnoldussen, I. A. C., Wiesmann, M., Pelgrim, C. E., Wielemaker, E. M., van Duyvenvoorde, W., Amaral-Santos, P. L., Verschuren, L., Keijser, B. J. F., Heerschap, A., Kleemann, R., Wielinga, P. Y., & Kiliaan, A. J.
Affiliations: Radboud University Nijmegen (NL)
Netherlands Organisation for Applied Scientific Research (NL)
ORCID: Arnoldussen, I A C
Wiesmann, M
Pelgrim, C E
Verschuren, L
Keijser, B J F
Heerschap, A
Kleemann, R
Kiliaan, A J
Venue: International Journal of Obesity
Publisher: Springer Science and Business Media LLC
Published: 2017-02-21
Volume: 41
Issue: 6
Pages: 935-944
ISSN: 0307-0565 (ISSN-L)
1476-5497
DOI: 10.1038/ijo.2017.52
OpenAlex: W2590130858
Cited by: 101
References: 51
Citations by year: 2026: 5 · 2025: 13 · 2024: 10 · 2023: 18 · 2022: 12 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 2
FWCI: 3.13
Type: journal article
Language: en
Open access: green
research.wur.nl
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: International Journal of Obesity (publishedVersion)
PubMed (publishedVersion)
Socio-Environmental Systems Modeling (acceptedVersion)
TNO Repository (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: Radboud Universitair Medisch Centrum
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords: butyrate, high-fat diet, midlife obesity, dementia, cognitive impairment, brain function, brain metabolism, neuroinflammation, cerebral blood flow, brain functional connectivity, gut microbiota, liver fibrosis, LDL receptor knockout mice, dietary intervention
MeSH terms: Animals, Butyrates, Cerebrovascular Circulation, Cognition Disorders, Disease Models, Animal, Hypertension, Inflammation, Liver Cirrhosis, Male, Mice, Obese, Neuroprotective Agents, Adiposity, Mice, Diet, High-Fat

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Butyrate restores HFD-induced adaptations in brain function and metabolism in mid-adult obese mice

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