Cited by 2,204Gut microbiota and healthAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

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Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice

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Gao, Zhanguo, Yin, Jun, Zhang, Jin, Ward, Robert E., Martin, Roy J., Lefevre, Michael, Cefalu, William T., Ye, Jianping·2009·Diabetes

DOI 10.2337/db08-1637PMC PMC2699871

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Abstract

OBJECTIVE: We examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet. RESEARCH DESIGN AND METHODS: In dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice. RESULTS: On the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a reduction in adiposity. CONCLUSIONS: Dietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function.

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Authors: Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J.
Affiliations: Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana;
Pennington Biomedical Research Center (US)
Utah State University (US)
Corresponding author: Ye, Jianping
ORCID: Yin, Jun
Ward, Robert E.
Martin, Roy J.
Cefalu, William T.
Ye, Jianping
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2009-04-14
Volume: 58
Issue: 7
Pages: 1509-1517
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db08-1637
PMC: PMC2699871
OpenAlex: W2101209169
Cited by: 2,204
References: 38
Citations by year: 2026: 129 · 2025: 187 · 2024: 200 · 2023: 198 · 2022: 213 · 2021: 206 · 2020: 229 · 2019: 168 · 2018: 149 · 2017: 115 · 2016: 119 · 2015: 98 · 2014: 58 · 2013: 43 · 2012: 33
FWCI: 12.09
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 4518 d)
Locations: Diabetes (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health (DK072476)
National Institute of Diabetes and Digestive and Kidney Diseases (DK072476, R56DK068036, R01DK068036, DK 68036, P30DK072476)
National Center for Complementary and Integrative Health (P50AT002776, P50 AT02776-020002)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: butyrate, short-chain fatty acids, insulin sensitivity, insulin resistance, energy expenditure, high-fat diet, obesity, thermogenesis, mitochondrial biogenesis, brown adipose tissue, skeletal muscle, AMPK, p38 MAPK, PGC-1α, type I muscle fibers, gut fermentation, dietary supplementation
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Body Temperature, Adipose Tissue, Brown, Butyrates, Dietary Fats, Energy Metabolism, Histone Deacetylases, Insulin, Insulin Resistance, Mice, Inbred C57BL, Mitochondria, Muscle, Obesity, Transcription Factors, Trans-Activators, Muscle, Skeletal, Muscle Fibers, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Metabolic Syndrome, Mice

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Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice

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