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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.
Diabetologia 2015; 58(9):2096-105D

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.

Authors+Show Affiliations

Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 152-050, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26105792

Citation

Jung, Tae Woo, et al. "BAIBA Attenuates Insulin Resistance and Inflammation Induced By Palmitate or a High Fat Diet Via an AMPK-PPARδ-dependent Pathway in Mice." Diabetologia, vol. 58, no. 9, 2015, pp. 2096-105.
Jung TW, Hwang HJ, Hong HC, et al. BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK-PPARδ-dependent pathway in mice. Diabetologia. 2015;58(9):2096-105.
Jung, T. W., Hwang, H. J., Hong, H. C., Yoo, H. J., Baik, S. H., & Choi, K. M. (2015). BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK-PPARδ-dependent pathway in mice. Diabetologia, 58(9), pp. 2096-105. doi:10.1007/s00125-015-3663-z.
Jung TW, et al. BAIBA Attenuates Insulin Resistance and Inflammation Induced By Palmitate or a High Fat Diet Via an AMPK-PPARδ-dependent Pathway in Mice. Diabetologia. 2015;58(9):2096-105. PubMed PMID: 26105792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK-PPARδ-dependent pathway in mice. AU - Jung,Tae Woo, AU - Hwang,Hwan-Jin, AU - Hong,Ho Cheol, AU - Yoo,Hye Jin, AU - Baik,Sei Hyun, AU - Choi,Kyung Mook, Y1 - 2015/06/24/ PY - 2015/02/04/received PY - 2015/05/21/accepted PY - 2015/6/25/entrez PY - 2015/6/25/pubmed PY - 2016/6/11/medline SP - 2096 EP - 105 JF - Diabetologia JO - Diabetologia VL - 58 IS - 9 N2 - 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. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/26105792/BAIBA_attenuates_insulin_resistance_and_inflammation_induced_by_palmitate_or_a_high_fat_diet_via_an_AMPK_PPARδ_dependent_pathway_in_mice_ L2 - https://doi.org/10.1007/s00125-015-3663-z DB - PRIME DP - Unbound Medicine ER -