Phenotype Information for Diet-Induced Obese C57BL/6J (380050)

JAX® Mice Strain - B6 DIO

Stock Number 380050

DIO Phenotypic Data

DIO C57BL/6J mice do not develop overt type 2 diabetes, but they model early stages of the disease with phenotypes that include:

  • Obesity (Figure 1 and Table 1)
  • Mildly elevated non-fasting blood glucose (Figure 2)
  • Glucose intolerance that increases with age (Figure 3)
  • Elevated serum total cholesterol, HDL cholesterol, glucose, and triglycerides (Table 2)

Diets were supplied by Research Diets, Inc. Spleen flow cytometry data are also available (Table 3). 

Complete results are available from the Mouse Phenome Database.

 dio_weight

Figure 1 Body weight growth curve. Male C57BL/6J DIO mice were fed D12492 60 kcal% fat and Control mice were fed D12450B 10 kcal% fat diet between the ages of 6 and 30 weeks. Values represent mean and one standard deviation of at least 40 mice per diet and age, measured on the same day each week.

 dio_glucose

Figure 2 Non-fasted glucose. Blood glucose levels of C57BL/6J males fed either D12492 60 kcal% fat (DIO) or D12450B 10 kcal% fat (Control) diet between the ages of 6 and 30 weeks. Submandibular blood glucose measurements were obtained using a OneTouch Ultra 2 or UltraMini hand-held glucometer that was validated with a control glucose solution on each day of use. Values represent mean and one standard deviation of at least 40 non-fasted mice per diet and age.

 dio_glucose_tolerance

Figure 3 Glucose tolerance tests. Blood glucose levels during glucose tolerance tests (GTT) at 8 weeks (A) and 16 weeks (B) of age. Following a 16 hour fast, an initial submandibular blood glucose reading was taken and mice were administered glucose by IP injection at 2g/kg body weight.  Blood glucose was measured in 30 minute intervals. Values represent mean and one standard deviation of 20 mice per diet and time point.  GTT performed on DIO mice at 26 weeks gave similar results as the 16 week timepoint (not shown).

Table 1 Body Composition. Mice were weighed and then analyzed using a Lunar PIXImus DEXA scanner. Calculations of body composition exclude the head. Values represent mean and one standard deviation of 10 non-fasted mice per diet and age. Results were analyzed by age using two-way ANOVA with Sidak’s multiple comparisons test to identify values that differed significantly between diet groups, using GraphPad Prism version 6.07 for Windows (GraphPad Software).

Age (weeks) Group Body Weight (g) Bone Mineral Density (g/cm2) Bone Mineral Content (g) Bone Area (cm2) Lean Tissue (g) Fat Tissue (g) Percent Fat Tissue

8

DIO

28.1 +/- 2.1a

0.052 +/- 0.002

0.416 +/- 0.028

7.97 +/- 0.39

19.8 +/- 1.2b

8.4 +/- 1.1a

30.0 +/- 1.8a

Control

23.4 +/- 1.3a

0.054 +/- 0.001

0.434 +/- 0.031

8.11 +/- 0.44

18.1 +/- 1.2b

5.3 +/- 0.8a

22.6 +/- 3.2a

16

DIO

41.5 +/- 3.4a

0.057 +/- 0.002

0.528 +/- 0.046

9.33 +/- 0.95

22.0 +/- 1.4

19.5 +/- 3.8a

46.6 +/- 5.7a

Control

30.8 +/- 2.5a

0.059 +/- 0.003

0.458 +/- 0.147

8.60 +/- 0.56

22.0 +/- 2.0

8.8 +/- 2.4a

28.6 +/- 6.3a

26

DIO

51.8 +/- 3.5a

0.053 +/- 0.053

0.536 +/- 0.045

10.06 +/- 0.79

23.9 +/- 1.5

27.8 +/- 2.8a

53.8 +/- 2.6a

Control

38.1 +/- 2.8a

0.058 +/- 0.002

0.532 +/- 0.031

9.20 +/- 0.38

22.9 +/- 1.2

15.2 +/- 2.1a

39.8 +/- 3.1a

a P ≤ 0.0001 b P ≤ 0.05

Table 2 Clinical chemistry. All values were measured from serum collected from submandibular blood except HbA1c, which was measured from submandibular whole blood. Values represent mean and one standard deviation of 10-20 non-fasted mice per age and diet group. Results were obtained using a Beckman Coulter AU680 chemistry analyzer. Results were analyzed by age using two-way ANOVA with Sidak’s multiple comparisons test to identify values that differed significantly between diet groups, using GraphPad Prism version 6.07 for Windows (GraphPad Software).

Age (weeks) Group Total Cholesterol (mg/dL) HDL Cholesterol (mg/dL) LDL Cholesterol (mg/dL) Triglycerides (mg/dL) Free Fatty Acids (mEq/L) Glucose (mg/dL) HbA1c (NGSP %)

8

DIO

173 +/- 23

135 +/- 17

4.6 +/- 0.7

138 +/- 44

1.13 +/- 0.29

215 +/- 39

5.7 +/- 0.3

Control

160 +/- 17

128 +/- 11

4.8 +/- 1.0

119 +/- 45

1.21 +/- 0.29

221 +/- 28

5.7 +/- 0.3

16

DIO

211 +/- 18a

150 +/- 10b

5.2 +/- 0.7

155 +/- 50a

1.18 +/- 0.24

249 +/- 44a

6.4 +/- 0.4

Control

161 +/- 23a

121 +/- 13b

5.9 +/- 1.0

106 +/- 30a

0.96 +/- 0.24

202 +/- 25a

5.8 +/- 0.6

26

DIO

257 +/- 45a

168 +/- 23c

9.8 +/- 3.4

152 +/- 34a

1.02 +/- 0.28

230 +/- 49b

6.7 +/- 0.2

Control

191 +/- 25a

139 +/- 13c

7.4 +/- 1.8

98 +/- 26a

0.81 +/- 0.19

195 +/- 22b

6.1 +/- 0.3

a P ≤ 0.0001 b P ≤ 0.001 c P ≤ 0.01

Table 3 Spleen Flow Cytometry. All cell populations are calculated as percentages of the total viable splenocyte population, except for regulatory T cells that are calculated as the percentage of viable CD4+ cells. Values represent mean and one standard deviation of 10 mice per age and diet group. Parameters were measured using a BD Biosciences LSR II flow cytometer.

Age (weeks) Group B Cells (B220+) T Cells (CD3e+) Helper T Cells (CD3e+, CD4+) Cytotoxic T Cells (CD3e+, CD8+) Regulatory T Cells (CD3e+, CD4+, CD25+) NK T Cells (CD3e+, CD49b+)

8

DIO

58.9 +/- 2.6

23.7 +/- 1.8

14.5 +/- 1.3

8.04 +/- 0.65

12.3 +/- 0.8

0.25 +/- 0.03

Control

58.4 +/- 2.4

26.7 +/- 2.7

16.7 +/- 1.8

8.87 +/- 0.88

12.8 +/- 0.6

0.31 +/- 0.08

16

DIO

65.4 +/- 5.5

20.8 +/- 2.5

12.2 +/- 1.6

7.19 +/- 0.89

16.0 +/- 1.2

0.19 +/- 0.03

Control

61.2 +/- 3.6

22.8 +/- 4.4

13.4 +/- 2.8

7.96 +/- 1.61

16.8 +/- 1.8

0.19 +/- 0.02

26

DIO

65.1 +/- 2.5

18.5 +/- 1.3

10.9 +/- 0.9

6.30 +/- 0.70

15.9 +/- 1.2

0.13 +/- 0.03

Control

63.6 +/- 1.9

23.7 +/- 2.0

13.8 +/- 1.5

8.45 +/- 0.69

15.8 +/- 0.8

0.17 +/- 0.04

Age (weeks) Group Monocytes 
(CD11b+, SSClo, Gr1-)
NK Cells
(CD3-, B220-, CD49b+)
Dendritic Cells (CD11b+, SSClo, CD11c+) Neutrophils/Granulocytes (CD11b+, Gr-1+) Eosinophils (CD11b+, SSChi) Plasmacytoid Dendritic Cells (B220+, CD11c+)

8

DIO

 1.16 +/- 0.18

 1.33 +/- 0.17

0.68 +/- 0.10

5.66 +/- 0.93

0.11 +/- 0.02

1.50 +/- 0.09

Control

 1.17 +/- 0.18

 1.59 +/- 0.16

0.60 +/- 0.08

3.61 +/- 0.94

0.10 +/- 0.02

1.43 +/- 0.30

16

DIO

 1.22 +/- 0.23

 0.94 +/- 0.12

0.63 +/- 0.13

4.02 +/- 1.05

0.17 +/- 0.06

0.98 +/- 0.17

Control

 1.50 +/- 0.39

 1.22 +/- 0.17

0.51 +/- 0.09

4.59 +/- 1.26

0.23 +/- 0.09

0.87 +/- 0.26

26

DIO

 1.45 +/- 0.21

 0.66 +/- 0.11

0.55 +/- 0.09

3.14 +/- 0.42

0.13 +/- 0.03

0.83 +/- 0.25

Control

 1.16 +/- 0.23

 0.99 +/- 0.15

0.64 +/- 0.10

2.68 +/- 0.53

0.12 +/- 0.04

0.96 +/- 0.25

Effect of Rosiglitazone on DIO Mice

Rosiglitazone is an anti-diabetic drug commonly used as a reference compound in metabolic research. The following conclusions come from a study performed by In Vivo Pharmacology Services at The Jackson Laboratory to examine the effects of rosiglitazone on the C57BL/6J DIO model. Starting at 20 weeks of age, male C57BL/6J DIO mice were dosed for 6 weeks with either 25mg/kg rosiglitazone or vehicle alone. 

  • Rosiglitazone improved glucose tolerance in C57BL/6J DIO mice (Figure 1)
  • Insulin sensitivity increased in response to rosiglitazone (Figure 2)
  • Rosiglitazone treatment led to increased body weight (Figure 3)
Fig 1

Figure 1. Oral Glucose Tolerance Test (OGTT) of male DIO mice (n=20). After 6 weeks of treatment, mice were fasted for 16 hours and dosed with 2g/kg glucose by oral gavage. Mean blood glucose levels were measured by tail tip bleed at 15, 30, 60, 90 and 120 minutes post administration.

Fig 2

Figure 2. Homeostasis model assessment as an index of insulin resistance (HOMA-IR) for male DIO mice treated for 6 weeks. Rosiglitazone significantly improved insulin sensitivity (p = 0.000236).

Fig 3

Figure 3. Body weight of male DIO mice (n=20) fed 60 kcal% fat diet and treated subcutaneously for 6 weeks. The weight drop observed at 38 days of treatment corresponds with a 16 hour fasting period required for OGTT.