Fig 1.
Biosynthesis pathway of n-6 polyunsaturated fatty acids.
Fig 2.
Structure of compound-326.
Table 1.
In vitro IC50 values (nM) for fatty acid desaturases.
Fig 3.
Effects of chronic treatment with compound-326 on BW, calorie intake, and blood PD markers in DIO mice.
DIO mice (initial BW; 31.1±1.6 g) were treated with compound-326 (0.1, 1, and 10 mg/kg), 30 mg/kg sibutramine, or vehicle p.o. for 6 weeks. (A) Changes in BW from initial value. (B) Daily calorie intake during the study. (C) Changes in blood AA and DGLA concentrations after 6-week treatment. (D) Changes in the blood AA to DGLA ratio after 6-week treatment. Data are expressed as mean ± SE (n = 7). #p≤ 0.025 vs. DIO vehicle by Williams' test. §p≤ 0.025 vs. DIO vehicle by Shirley-Williams test. *p≤ 0.05, **p≤ 0.01 vs. DIO vehicle by Aspin-Welch test. ¶p≤ 0.05, ¶¶p≤ 0.01 vs. DIO vehicle by Student's t-test.
Fig 4.
Effects of chronic treatment with compound-326 on plasma glucose and insulin during an OGTT, and HOMA-IR in DIO mice.
Oral glucose tolerance test (OGTT) was performed after chronic treatment with compound-326 for 6 weeks in DIO mice. (A) Changes in plasma glucose levels. (B) Effect on plasma glucose AUC. (C) Changes in plasma insulin levels. (D) Effect on HOMA-IR. Data are expressed as mean ± SE (n = 7). §p≤ 0.025 vs. DIO vehicle by Shirley-Williams test. ¶p≤ 0.05 vs. DIO vehicle by Student's t-test.
Fig 5.
Effects of chronic treatment with compound-326 on BW, calorie intake, and fat mass in DIO mice.
DIO mice were treated with 10 mg/kg compound-326, p.o., for 11 weeks. (A) Changes in BW. (B) Changes in daily calorie intake. (C) Weights of different body fat depots after 11-week treatment. Data are expressed as mean ± SE (n = 7). *p≤ 0.05, **p≤ 0.01 vs. DIO vehicle by Aspin-Welch test. ¶p≤ 0.05, ¶¶p≤ 0.01 vs. DIO vehicle by Student's t-test.
Fig 6.
Effect of chronic treatment with compound-326 on energy expenditure in DIO mice.
Daily energy expenditure (DEE) was monitored on days 1 (A), 8 (B), 15 (C), 21 (D), and 56 (E) during the study indicated in Fig 5.
Fig 7.
Effects of chronic treatment with compound-326 on PD markers and gene expression in WAT in DIO mice.
HFD-fed DIO mice were treated with compound-326 (10 mg/kg), p.o. for 6 weeks. Mice fed a normal diet (ND) were used as normal reference. (A) Levels of AA and DGLA in epididymal adipose tissue. (B) AA to DGLA ratio in epididymal adipose tissue. RT-qPCR was performed in epididymal (C) and subcutaneous fat tissues (D) after 6-week treatment. Data are expressed as mean ± SE (n = 8–9). *p≤ 0.05, **p≤ 0.01 vs. DIO vehicle by Aspin-Welch test. ¶p≤ 0.05, ¶¶p≤ 0.01 vs. DIO vehicle by Student's t-test.