The present work provides evidences that Embelin is effective in inhibiting adipogenesis and lipogenesis in vitro and the mechanisms may involve canonical Wnt signaling. Embelin has the potential to prevent body weight gain and fat accumulation, and to improve obesity-related glucose tolerance impairment and insulin resistance in the HFD-fed mice.
Background Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This can be prevented by the PPAR-γ agonist pioglitazone through its anti-oxidant and anti-inflammatory effects. Purpose In this study, the molecular mechanisms underlying these effects were investigated. Methods Rabbits were randomly divided into control (C), diabetic (DM), and pioglitazone-treated DM (Pio) groups. Echocardiographic, hemodynamic, electrophysiological, intracellular Ca2+ properties were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of pro-fibrotic marker transforming growth factor β1 (TGF-β1), and the mitochondrial proteins (PGC-1α, fission and fusion-related proteins) were measured. Results Compared with controls, the DM group demonstrated larger left atrial diameter and fibrosis area associated with a higher incidence of inducible AF. Lower serum PPAR-γ level was associated with lower PGC-1α, higher NF-κB and higher TGF-β1 expression. Mn-SOD protein was not different but lower mitochondrial fission- and fusion-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, lower MMP and higher intracellular Ca2+ transients were observed. In the Pio group, reversal of structural remodeling and lower inducible AF incidence were associated with higher PPAR-γ and PGC-1α. NF-κB and TGF-β1 were lower and biogenesis, fission and fusion-related protein were higher. Mitochondrial structure and function, and intracellular Ca2+ transients were improved. In HL-1 cell line, transfected with PGC-1α siRNA blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells. Conclusion Diabetes mellitus induces adverse atrial structural and electrophysiological remodeling, abnormal Ca2+ handling and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway. Acknowledgement/Funding National Natural Science Foundation of China (No 81570298, 81270245, 30900618 to T.L.)
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