PPAR-α–Null Mice Are Protected From High-Fat Diet–Induced Insulin Resistance
Article Figures & Tables
Figures
- FIG. 1.
Effect of high-fat feeding on plasma glucose and insulin. Plasma glucose and insulin concentrations were measured in blood obtained from the orbital sinus of mice that had been food-deprived for 4 h. Wild-type and PPAR-α–null Sv/129 mice were fed either standard diet (□; n = 8 per genotype) or high-fat diet (▪; n = 8 per genotype) for 22 weeks. Data represent mean ± SE. *P < 0.01 versus standard diet.
- FIG. 2.
Relationship between leptin and adipose tissue weight. Plasma leptin was plotted against the epididymal adipose tissue weight for wild-type (triangles) and PPAR-α–null (circles) Sv/129 and C57BL/6 mice, fed either standard diet (open symbols) or high-fat diet (closed symbols).
- FIG. 3.
Effect of high-fat feeding on ITT. Intraperitoneal ITTs were performed in Sv/129 wild-type (○) and PPAR-α–null (•) mice fed either standard or high-fat diet for 22 weeks. Data are expressed relative to time 0 and represent the means ± SE of seven independent tests. Response curves were compared by two-way analysis of variance. The diet effect was statistically significant (P < 0.01) in wild-type mice. The genotype effect was statistically significant (P < 0.05) in high-fat–fed mice.
- FIG. 4.
Effect of high-fat feeding on GTT. Intraperitoneal GTTs were performed in Sv/129 wild-type (○) and PPAR-α–null (•) mice fed either standard or high-fat diet for 22 weeks. Data are expressed as changes relative to time 0 and represent the means ± SE of five independent tests.
- FIG. 5.
Insulin secretion in isolated islets. Insulin secretion was measured in static incubations of isolated islets from wild-type and PPAR-α–null mice on the C57BL/6N genetic background fed standard diet (□) or high-fat diet (▪) for 16 weeks. Data are the means ± SE of three (high-fat diet) and five (standard diet) separate incubations.
Tables
- TABLE 1
Effect of long-term high-fat feeding in wild-type and PPAR-α–null mice on two genetic backgrounds
C57BL/6N mice Sv/129 mice Wild-type PPAR-α–null Wild-type PPAR-α–null Standard diet (n = 6) High-fat diet (n = 6) Standard diet (n = 6) High-fat diet (n = 6) Standard diet (n = 8) High-fat diet (n = 8) Standard diet (n = 8) High-fat diet (n = 8) Food intake (kcal · kg−1 · day−1) 465 ± 28.5 511 ± 15.2 506 ± 21.0 560 ± 28.9 383 ± 7.35 414 ± 13.3 369 ± 11.6 386 ± 22.4 Body weight (g) 32.7 ± 0.95 38.0 ± 1.37† 30.8 ± 0.94 32.4 ± 0.78 27.1 ± 0.80 34.5 ± 1.28† 29.6 ± 0.70 33.1 ± 0.90 Liver weight (g) 1.46 ± 0.12 1.44 ± 0.10 1.50 ± 0.07 1.48 ± 0.11 1.00 ± 0.03 1.26 ± 0.05† 1.26 ± 0.08 1.95 ± 0.10† Adiposity index* (%) 1.60 ± 0.33 3.58 ± 0.34† 1.71 ± 0.25 3.74 ± 0.40† 2.94 ± 0.23 6.34 ± 0.78† 3.42 ± 0.36 5.93 ± 0.52† Plasma glucose (mmol/l) 9.8 ± 0.67 11.5 ± 0.75 10.6 ± 0.72 9.3 ± 0.42 9.6 ± 0.56 11.6 ± 0.58 9.1 ± 0.41 8.2 ± 0.65 Plasma insulin (pmol/l) 209 ± 21.3 398 ± 50.1† 189 ± 31.8 225 ± 30.2 215 ± 23.9 378 ± 38.8† 284 ± 26.9 256 ± 32.3 Data are means ± SE. Mice on the C 57BL/6N genetic background were fed the high-fat diet for 16 weeks. Mice on the Sv/129 genetic background were fed the high-fat diet for 22 weeks.
- *
* Adiposity index was the ratio of epididymal adipose tissue to body weight for C57BL/6N mice and the ratio of epididymal + inguinal adipose tissue to body weight for Sv/129 mice.
- †
† P < 0.05 versus standard diet.
- TABLE 2
Effect of high-fat feeding on IR index
Wild-type PPAR-α–null Standard diet (n = 5) High-fat diet (n = 5) Standard diet (n = 6) High-fat diet (n = 5) AUC glucose (mg/dl · 2 h) 115 ± 15 296 ± 78* 106 ± 16 128 ± 27 AUC insulin (ng/dl · 2 h) 17.3 ± 3.1 27.6 ± 2.7* 23.2 ± 6.3 12.8 ± 2.5 IR Index (AUC glucose · AUC insulin) 1,970 ± 413 8,400 ± 2,790* 2,490 ± 730 1,680 ± 548 Data are means ± SE. Areas under the insulin and glucose curves were calculated from the data shown in Fig. 4. The IR index is the product of glucose and insulin AUCs.
- *
* P < 0.05 versus standard diet.
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