Abstract | AIMS/HYPOTHESIS: 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:
|
Authors | Tae Woo Jung, Hwan-Jin Hwang, Ho Cheol Hong, Hye Jin Yoo, Sei Hyun Baik, Kyung Mook Choi |
Journal | Diabetologia
(Diabetologia)
Vol. 58
Issue 9
Pg. 2096-105
(Sep 2015)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 26105792
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Aminoisobutyric Acids
- Fatty Acids
- Insulin
- NF-kappa B
- Palmitates
- Ppard protein, mouse
- RNA, Small Interfering
- Receptors, Cytoplasmic and Nuclear
- Carnitine O-Palmitoyltransferase
- AMP-Activated Protein Kinases
- Oxygen
- 3-aminoisobutyric acid
|
Topics |
- AMP-Activated Protein Kinases
(metabolism)
- Active Transport, Cell Nucleus
- Aminoisobutyric Acids
(chemistry)
- Animals
- Carnitine O-Palmitoyltransferase
(metabolism)
- Diabetes Mellitus
(metabolism)
- Diet, High-Fat
(adverse effects)
- Fatty Acids
(chemistry)
- Gene Expression Regulation
- Glucose Tolerance Test
- Inflammation
(physiopathology)
- Insulin
(metabolism)
- Insulin Resistance
- Male
- Mice
- Mice, Inbred C57BL
- Muscle Fibers, Skeletal
(metabolism)
- NF-kappa B
(metabolism)
- Oxygen
(chemistry)
- Palmitates
(adverse effects)
- RNA, Small Interfering
(metabolism)
- Receptors, Cytoplasmic and Nuclear
(metabolism)
- Signal Transduction
|