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

Arnoldussen, Ilse A.C.; Wiesmann, Maximilian; Pelgrim, Charlotte E.; Wielemaker, E M; Duyvenvoorde, Wim van; Amaral-Santos, P L; Verschuren, Lars; Keijser, Bart J. F.; Heerschap, Arend; Kleemann, Robert; Wielinga, Peter Y.; Kiliaan, Amanda J.

doi:10.1038/ijo.2017.52

Cited by 88 publications

(110 citation statements)

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“…In fact, histone deacetylase inhibitors are being tested in several fibrosis-related diseases (43). Considering also that butyric, propionic, and acetic acid contribute to improve metabolism of glucose and lipids (14,44,45) and that butyrate restores high-fat diet-induced metabolic adaptations in obese mice (46), results presented herein provide new rationale for exploring prebiotic supplementation in patients with cirrhosis and chronic liver conditions leading to cirrhosis, such as nonalcoholic fatty liver disease or steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

et al. 2019

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Short‐chain fatty acids (SCFAs) are gut microbiota‐derived products that participate in maintaining the gut barrier integrity and host's immune response. We hypothesize that reduced SCFA levels are associated with systemic inflammation, endotoxemia, and more severe hemodynamic alterations in cirrhosis. Patients with cirrhosis referred for a hepatic venous pressure gradient (HVPG) measurement (n = 62) or a transjugular intrahepatic portosystemic shunt placement (n = 12) were included. SCFAs were measured in portal (when available), hepatic, and peripheral blood samples by GC‐MS. Serum endotoxins, proinflammatory cytokines, and NO levels were quantified. SCFA levels were significantly higher in portal vs. hepatic and peripheral blood. There were inverse relationships between SCFAs and the severity of disease. SCFAs (mainly butyric acid) inversely correlated with the model for end‐stage liver disease score and were further reduced in patients with history of ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis. There was an inverse relationship between butyric acid and HVPG values. SCFAs were directly related with systemic vascular resistance and inversely with cardiac index. Butyric acid inversely correlated with inflammatory markers and serum endotoxin. A global reduction in the blood levels of SCFA in patients with cirrhosis is associated with a more advanced liver disease, suggesting its contribution to disease progression.—Juanola, O., Ferrusquía‐Acosta, J., García‐Villalba, R., Zapater, P., Magaz, M., Marín, A., Olivas, P., Baiges, A., Bellot, P., Turon, F., Hernández‐Gea, V., González‐Navajas, J. M., Tomás‐Barberán, F. A., García‐Pagán, J. C., Francés, R. Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis. FASEB J. 33, 11595–11605 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

et al. 2019

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“…; Arnoldussen et al . ), and propionate is able to reduce anticipatory reward responses to high‐energy foods in the human striatum (Byrne et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…Considering the plethora of ways in which they can affect the host, it's not surprising that SCFAs have been implicated in numerous physiological functions such as gastrointestinal functionality, host metabolism, blood-pressure regulation, circadian rhythm and (neuro)immune function (Koh et al 2016;Erny et al 2017;Pluznick, 2017;Tahara et al 2018). Gut microbial-derived SCFAs are also increasingly implicated in emotional processing and behaviour, as butyrate has been shown to ameliorate cognitive impairments in a model of vascular dementia and in mid-adult high-fat-diet-induced obese mice Arnoldussen et al 2017), and propionate is able to reduce anticipatory reward responses to high-energy foods in the human striatum (Byrne et al 2016). Finally, correlations between SCFA levels and depressive-, anxietyand stress-related behaviours have been reported after prebiotic administration .…”

Section: Introductionmentioning

confidence: 99%

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Wouw

Boehme

Lyte

et al. 2018

The Journal of Physiology

543

309

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There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota-derived metabolites play a central role in the communication between microbes and their host, with short-chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.

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“…There is a growing interest in short-chain fatty acids—such as butyrate—as dietary intervention for obesity and related metabolic diseases [ 17 , 18 ]. Butyrate is one of the fatty acids produced during bacterial fermentation in the distal gut of nondigestible carbohydrates like dietary fiber and resistant starch.…”

Section: Introductionmentioning

confidence: 99%

Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice

Pelgrim¹,

Franx²,

Snabel

et al. 2017

Nutrients

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Adipose tissue (AT) has a modulating role in obesity-induced metabolic complications like type 2 diabetes mellitus (T2DM) via the production of so-called adipokines such as leptin, adiponectin, and resistin. The adipokines are believed to influence other tissues and to affect insulin resistance, liver function, and to increase the risk of T2DM. In this study, we examined the impact of intervention with the short-chain fatty acid butyrate following a high-fat diet (HFD) on AT function and other metabolic risk factors associated with obesity and T2DM in mice during mid- and late life. In both mid- and late adulthood, butyrate reduced HFD-induced adipocyte hypertrophy and elevations in leptin levels, which were associated with body weight, and cholesterol and triglyceride levels. HFD feeding stimulated macrophage accumulation primarily in epididymal AT in both mid- and late life adult mice, which correlated with liver inflammation in late adulthood. In late-adult mice, butyrate diminished increased insulin levels, which were related to adipocyte size and macrophage content in epididymal AT. These results suggest that dietary butyrate supplementation is able to counteract HFD-induced detrimental changes in AT function and metabolic outcomes in late life. These changes underlie the obesity-induced elevated risk of T2DM, and therefore it is suggested that butyrate has potential to attenuate risk factors associated with obesity and T2DM.

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

Cited by 88 publications

References 50 publications

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice

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