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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
Open accessAbstract
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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“BAIBA promotes increased VAT lipolysis, increased FFA oxidation, and glucose uptake in SkM [110,111,112].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [111]
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“For example, β‐aminoisobutyric acid (BAIBA), a novel exercise‐induced muscle factor, attenuates insulin resistance, improves glucose tolerance, and promotes the browning of white adipose tissue (WAT) and hepatic β‐oxidation (Roberts et al, 2014; Jung et al, 2015).”
From Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation (2020) · cites this paper as Jung et al, 2015
In the citing paper
“In another study using C2C12 mouse myocytes and a wild-type mouse model (palmitate or high-fat diet exposure), BAIBA treatment attenuated insulin resistance, reduced inflammation and increased fatty acid oxidation through AMP-activated protein kinase (AMPK) and a AMPK-PPARδ-dependent pathway in skeletal muscle113.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [113]
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Metadata
- 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
- Venue
- Diabetologia
- Published
- 2015-06-24
- Volume
- 58
- Issue
- 9
- Pages
- 2096-2105
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- 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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