Effect of MHY908 on body weight, plasma glucose, TG, and insulin levels in db/db mice.

<p>Mice were treated for 4/kg/day in food. Food intakes and body weights were similar in the Con group and MHY908- treated groups (n = 8/group, eight-weeks old). (A) Changes in body weights. (B) A series of plasma profiles from CR and MHY908 treated db/db mice. One-factor ANOVA was used to determine the significances of differences: *** p<0.001, ** p<0.01 and * p<0.05 versus the Con group. Lean; db/m mice, Con; db/db mice, CR; calorie restriction, 1 mg; MHY 908 1 mg/kg/day, 3 mg; MHY 908 3 mg/kg/day.</p

MHY908 improved hepatic steatosis in db/db mouse livers.

<p>(A) A histological examination based on hematoxylin-eosin staining showed marked fatty changes in the livers of db/db mice. (Original magnification 100 X) (B) Accumulated lipids in the livers of MHY908-treated db/db mice. One-factor ANOVA was used to determine the significances of differences: *** p<0.001, ** p<0.01 and * p<0.05 versus the Con group. (C) CPT-1 expression was assessed by immunohistochemistry (Original magnification 200 X). Lean; db/m mice, Con; db/db mice, CR; calorie restriction, 1 mg; MHY 908 1 mg/kg/day, 3 mg; MHY 908 3 mg/kg/day.</p

Possible mechanism of the effects of MHY908 on overnutrition-induced insulin resistance.

<p>We suggest that overnutrition induced lipid accumulation and led to insulin resistance by increasing ER stress, and that MHY908 downregulated ER stress and improved insulin signaling in the livers of db/db mice.</p

Synthesis of MHY908.

<p>Reagents and conditions: (a) Ethyl-bromoisobutyrate, 1N-NaOEt, EtOH, reflux, 14 h, 72%; (b) Na₂S₂O₅, DMF, 80°C, 11 h, 31%; (c) 1N-NaOH, 1,4-dioxane, rt, 17 h, 79%; (d) 1N-NaOH, 1,4-dioxane, rt, 4 h, 99.9%; (e) NaOAc, AcOH, reflux, 1 h, 40%.</p

MHY908 modulated serum leptin and adiponectin levels in db/db mice.

<p>(A) Serum concentrations of leptin (n = 6) (B) Serum concentrations of adiponectin (n = 6) One-factor ANOVA was used to determine the significances of differences: *** p<0.001, ** p<0.01 and * p<0.05 versus the Con group. Lean; db/m mice, Con; db/db mice, CR; calorie restriction, 1 mg; MHY 908 1 mg/kg/day, 3 mg; MHY 908 3 mg/kg/day.</p

Detailed information on the hydrogen bonding networks formed by fenofibrate, rosiglitazone, and MHY908.

<p>Detailed information on the hydrogen bonding networks formed by fenofibrate, rosiglitazone, and MHY908.</p

Heptadecane attenuated NF-kB-responsive COX-2 and iNOS via NIK/IKK and MAPKs.

<p>YPEN-1 cells were grown to 80% confluent in 100 mm dishes in DMEM. Cells were pre-treated (1 hr) with heptadecane (20 µM) and inhibitors and then stimulated with 10 µM t-BHP. After stimulation with t-BHP in the absence (−) or presence (+) of heptadecane and each kinase inhibitor, COX-2 and iNOS gene expressions were determined in cell extracts.</p

Heptadecane suppressed expressions of NF-kB-dependent genes in aged rats.

<p>Western blot was performed to detect renal COX-2 and iNOS levels in cytoplasmic extracts (40 µg protein) from young, aged, and aged rats fed heptadecane. One representative blot of each protein is shown from three experiments that yielded similar results, respectively. Young rats (9 months of age) and aged (20 months of age) were utilized. Heptadecane was fed to aged rats at 2 mg or 4 mg/Kg per day for 10 days. Statistical significance: results of one-factor ANOVA: ***p<0.001 vs. young rat; ^#p<0.05, ^##p<0.01 vs. old non-heptadecane-fed rats, respectively.</p

Heptadecane suppressed the age-related activations of NIK/IKK and MAPKs.

<p>Western blot on renal cytoplasmic extracts (40 µg protein) from young, aged, and aged rats fed heptadecane. (A) Phosphorylations of P38 and JNK are designated p-p38 and p-JNK1/2. (B) Phosphorylations of NIK and IKK are designated p-NIK and p-IKKα/β. (C) Phosphorylations of MEK1/2 and ERK1/2 were detected using antibodies of p-MEK1/2 and p-ERK1/2. One representative blot of each protein from three experiments that yielded similar results is shown. Young rats (9 months of age) and aged (20 months of age) were utilized. Heptadecane was fed to aged rats at 2 mg or 4 mg/Kg per day for 10 days.</p

Heptadecane protected YPEN-1 cells from t-BHP-induced oxidative stress and cytotoxicity.

<p>(A) Cells were treated with or without/heptadecane at concentrations of 1, 5, 10, and 20 µM for 1 hr and then with vehicle or 10 µM t-BHP. (B) Cells were treated with or without heptadecane at concentrations of 1, 5, 10 and 20 µM for 1 hr and then with t-BHP (10 µM) for 6 hr. Viable cell numbers were determined using an MTT assay. ^##p<0.01 vs. vehicle treated control group; **p<0.01, ***p<0.001 vs. the 10 µM t-BHP group by one-factor ANOVA.</p