Cited by 145Peroxisome Proliferator-Activated ReceptorsMetabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic Diseases

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BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice

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Jung, Tae Woo, Hwang, Hwan-Jin, Hong, Ho Cheol, Yoo, Hye Jin, Baik, Sei Hyun, Choi, Kyung Mook·2015·Diabetologia

DOI 10.1007/s00125-015-3663-z

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Abstract

Aims/hypothesis We explored the effects of β-aminoisobutyric acid (BAIBA) on hyperlipidaemic-condition-induced insulin resistance and inflammation as mediated through a signalling pathway involving AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor δ (PPARδ). Methods Mouse skeletal muscle C2C12 cells and C57BL/6J mice were treated with palmitate or a high-fat diet (HFD) and BAIBA. Inflammation and the expression of genes associated with insulin signalling were determined by western blot and quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si)RNA knockdown and specific inhibitors. Results BAIBA treatment ameliorated impairment of insulin receptor substrate (IRS)-1/Akt-mediated insulin signalling in palmitate-treated C2C12 myocytes and in skeletal muscle of HFD-fed mice. In addition, BAIBA treatment reversed HFD-induced increases in body weight and improved impaired glucose tolerance in mice. In vitro and in vivo, inhibitory κBα (IκBα) phosphorylation, nuclear factor κB (NFκB) nuclear translocation and downstream inflammatory cytokines were significantly suppressed by BAIBA. Furthermore, BAIBA treatment significantly induced AMPK phosphorylation and expression of PPARδ in C2C12 myocytes and in skeletal muscle of mice. Both compound C, an AMPK inhibitor, and Pparδ (also known as Ppard) siRNA abrogated the inhibitory effects of BAIBA on palmitate-induced inflammation and insulin resistance. BAIBA significantly induced the expression of genes associated with fatty acid oxidation, such as carnitine palmitoyltransferase 1 (Cpt1), acyl-CoA oxidase (Aco; also known as Acox1) and fatty acid binding protein 3 (Fabp3); this effect of BAIBA was significantly reduced by compound C and Pparδ siRNA. Conclusions/interpretation These results are the first to demonstrate that BAIBA attenuates insulin resistance, suppresses inflammation and induces fatty acid oxidation via the AMPK-PPARδ pathway in skeletal muscle.

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Retracted
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Authors: Jung, T. W., Hwang, H.-J., Hong, H. C., Yoo, H. J., Baik, S. H., & Choi, K. M.
Affiliations: Korea University Guro Hospital (KR)
Corresponding author: Choi, Kyung Mook
ORCID: Jung, Tae Woo
Hwang, Hwan-Jin
Yoo, Hye Jin
Baik, Sei Hyun
Choi, Kyung Mook
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2015-06-24
Volume: 58
Issue: 9
Pages: 2096-2105
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-015-3663-z
OpenAlex: W2163244012
Cited by: 145
References: 35
Citations by year: 2026: 14 · 2025: 12 · 2024: 21 · 2023: 22 · 2022: 13 · 2021: 14 · 2020: 11 · 2019: 14 · 2018: 8 · 2017: 9 · 2016: 7
FWCI: 3.47
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: beta-aminoisobutyric acid, insulin resistance, inflammation, AMPK, PPARδ, palmitate, high-fat diet, skeletal muscle, fatty acid oxidation, NF-κB, compound C, carnitine palmitoyltransferase 1, acyl-CoA oxidase, fatty acid binding protein 3, glucose tolerance, hyperlipidemia
MeSH terms: Aminoisobutyric Acids, Animals, Carnitine O-Palmitoyltransferase, Diabetes Mellitus, Fatty Acids, Gene Expression Regulation, Glucose Tolerance Test, Inflammation, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Oxygen, Palmitates, Signal Transduction, NF-kappa B, Receptors, Cytoplasmic and Nuclear, Muscle Fibers, Skeletal, Active Transport, Cell Nucleus, RNA, Small Interfering, Mice, AMP-Activated Protein Kinases, Diet, High-Fat

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BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice

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