Review Article

An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus

Table 1

Considerations for designing a high fat diet protocol.

NotesReferences#

Design
 Length of dietAdaptive (<1 week)
Acute (<2 weeks)
Chronic (>8 weeks)
 FormulationMatching Human Western Diet
Accentuate pathology
 AgePathologies intensify with age
 GenderMales are predominantly used to avoid the female cycles
 StrainHyperglycemia susceptible: C57Bl/6J (C57Bl/6N healthier than C57Bl/6J after HFD), DBA2/J, BXD66 [12, 13, 4850]
Hyperglycemia resistant: MRL, Lrg, A/J, BXD77, BALB/cJ

Assessments
 WeightsWhole body and specific tissues: different adipocyte sites, liver, heart
 Weekly blood glucoseFasting versus fed, time of day
 Echocardiography
 Blood pressurePV loops versus noninvasive
 Glucose TTFasting versus fed, time of day, acute versus long term[44, 51]
Glucose delivery: oral, IP, or IV
 Insulin TTFasting versus fed, time of day, acute versus long term
 Serum collectionFasting versus fed, time of day
 DEXAAllows time course of body composition
 NMRAllows time course of body composition, more reliable than DEXA[44]
 HistologyFibrosis, picrosirius red, periodic acid shift, immune infiltrate, adipocyte, skeletal muscle, cardiac cell size
 FibrosisTGFβ, pSMAD2/3, αSMA, IL6, IL13, IL33[48]

Additional phenotypes
 Hyperglycemic clampIdentifies glucose sensitivity, by measuring serum insulin levels[44]
 Hyperinsulinemic-euglycemic clampConsiderations 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
 InflammationFlow cytometry for specific cell types [48]
Histology can also identify specific cells
Cytokine levels in serum or tissue extracts
 Liver, NAFLDAspartate transaminase and alanine transaminase
Progression of disease: steatosis > steatohepatitis > cirrhosis > HCC
 Electron micrographsAnalyze mitochondria and lipid storage sites in detail

TT, tolerance test; DEXA, duel-energy X-ray absorptiometry; HCC, hepatocellular carcinoma; IP, intraperitoneal; IV, intravenous; NAFLD, nonalcoholic fatty liver disease. #References are given where inappropriate.