|
| Notes | References# |
|
Design | | |
Length of diet | Adaptive (<1 week) | |
Acute (<2 weeks) | |
Chronic (>8 weeks) | |
Formulation | Matching Human Western Diet | |
Accentuate pathology | |
Age | Pathologies intensify with age | |
Gender | Males are predominantly used to avoid the female cycles | |
Strain | Hyperglycemia susceptible: C57Bl/6J (C57Bl/6N healthier than C57Bl/6J after HFD), DBA2/J, BXD66 | [12, 13, 48–50] |
Hyperglycemia resistant: MRL, Lrg, A/J, BXD77, BALB/cJ |
|
Assessments | | |
Weights | Whole body and specific tissues: different adipocyte sites, liver, heart | |
Weekly blood glucose | Fasting versus fed, time of day | |
Echocardiography | | |
Blood pressure | PV loops versus noninvasive | |
Glucose TT | Fasting versus fed, time of day, acute versus long term | [44, 51] |
Glucose delivery: oral, IP, or IV |
Insulin TT | Fasting versus fed, time of day, acute versus long term | |
Serum collection | Fasting versus fed, time of day | |
DEXA | Allows time course of body composition | |
NMR | Allows time course of body composition, more reliable than DEXA | [44] |
Histology | Fibrosis, picrosirius red, periodic acid shift, immune infiltrate, adipocyte, skeletal muscle, cardiac cell size | |
Fibrosis | TGFβ, pSMAD2/3, αSMA, IL6, IL13, IL33 | [48] |
|
Additional phenotypes | | |
Hyperglycemic clamp | Identifies glucose sensitivity, by measuring serum insulin levels | [44] |
Hyperinsulinemic-euglycemic clamp | Considerations are time of clamp and how tightly to regulate the glucose infusions | [44, 52, 53] |
Determines glucose use |
Tissue specific glucose uptake | Used in conjunction with the above clamp techniques | [44] |
Requires an MRI and radioactively labeled energy sources |
Much easier in rats |
Determines insulin sensitivity in multiple tissues |
Inflammation | Flow cytometry for specific cell types | [48] |
Histology can also identify specific cells |
Cytokine levels in serum or tissue extracts |
Liver, NAFLD | Aspartate transaminase and alanine transaminase | |
Progression of disease: steatosis > steatohepatitis > cirrhosis > HCC | |
Electron micrographs | Analyze mitochondria and lipid storage sites in detail | |
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