Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit
Open accessAbstract
Objective: Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Design: Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice. Results: Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT. Conclusion: Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT.
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SCFAs have an important role in the prevention and treatment of obesity-associated insulin resistance in animal studies.
“Animal studies suggest that SCFAs have an important role in the prevention and treatment of obesity-associated insulin resistance (89, 114, 191, 192).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [89]
The introduction says butyrate supplementation can prevent high-fat-diet-induced obesity and insulin resistance, and the results report lower insulin resistance in butyrate-treated mice. The discussion proposes butyrate as a strategy to combat obesity-related disease, but the study does not demonstrate treatment of established insulin resistance or the same benefit across SCFAs generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSCFAs enhance sleep, suppress the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and modulate signaling triggered by the ghrelin receptor, contributing to circadian rhythm and appetite control.
“Further, SCFAs show effects on several neural functions, such as enhancing sleep (10), suppressing the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus (89), and modulating the signaling triggered by the ghrelin receptor (129), contributing to circadian rhythm and appetite control.”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [89]
SCFAs are associated with a variety of diseases such as rectal cancer, pancreatitis, abnormal energy metabolism, constipation, blood lipid metabolism, sleep disorders and Alzheimer's disease.
“Studies have found that SCFAs are associated with a variety of diseases such as rectal cancer, 174 pancreatitis, 175 abnormal energy metabolism, 176 constipation, 177 blood lipid metabolism, 178 sleep disorders 179 and Alzheimer's disease.180”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [176]
Activation of FFA3 receptors on vagus nerve cells can activate various CNS neurons, including dynamic regulation of hypothalamic neuronal circuitry.
“Activation of FFA3 receptors on vagus nerve cells can result in the activation of various neurons in the CNS, including dynamic regulation of hypothalamic neuronal circuitry (287).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [287]
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- Authors
- Li, Z., Yi, C.-X., Katiraei, S., Kooijman, S., Zhou, E., Chung, C. K., Gao, Y., van den Heuvel, J. K., Meijer, O. C., Berbée, J. F. P., Heijink, M., Giera, M., Willems van Dijk, K., Groen, A. K., Rensen, P. C. N., & Wang, Y.
- Affiliations
- Leiden University Medical Center (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
- University of Groningen (NL)
- Corresponding author
- Wang, Yanan
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-11-03
- Volume
- 67
- Issue
- 7
- Pages
- 1269-1279
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2765733390
- Semantic Scholar
- 3a9a0df94b76abc1b5b1498f67141e19d318c8bf
- Cited by
- 674
- References
- 48
- Citations by year
- 2026: 50 · 2025: 107 · 2024: 101 · 2023: 95 · 2022: 102 · 2021: 82 · 2020: 65 · 2019: 50 · 2018: 19 · 2017: 1
- FWCI
- 22.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Universiteit Leiden
- Leids Universitair Medisch Centrum
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- butyrate, appetite, brown adipose tissue, vagotomy, dietary intake, neuropeptide Y, hypothalamus, nucleus tractus solitarius, dorsal vagal complex, energy expenditure, fat oxidation, diet-induced obesity, hyperinsulinemia, hepatic steatosis, high-fat diet, sympathetic outflow, short-chain fatty acids
- MeSH terms
- Administration, Oral, Animals, Appetite, Adipose Tissue, Brown, Butyrates, Energy Intake, Energy Metabolism, Injections, Intravenous, Male, Satiety Response, Mice
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