Table 2.
A comparison of PPARγ knockout models specific to metabolic tissues.
| Targeted tissue (type of knock-out) |
Adiposity | Plasma profile | Adipokine production | Liver steatosis | Insulin resistance |
Other phenotype |
|---|---|---|---|---|---|---|
|
Adipose[26,78-83] (hypomorph[26,78]; w/ aP2- Cre[79,80]; aP2-Cre-ERT2[81]; PPARγ2-KO[82,83]) |
Congenital lipodystrophy[78] Progressive lipodystrophy[79,81] Moderate lipodystrophy[82] Normal adiposity[83] |
↑Glc & ↑Ins[78,83] Normal Glc & Ins[79,82] ↑TG, ↑FFA[78,79] ↓TG[81] Normal TG & Chol[82] or FFA[83] |
↓Leptin[78,79,82] ↑Leptin[83] ↓Adiponectin[26,78-80,82,83] |
Normal liver TG[78,82,83] Steatosis[79] |
Yes[78,79,82,83] | ↑Bone mass[26] |
|
Muscle[84,85] (w/ MCK-Cre) |
↑Adipose mass[84] (↑)Adipose mass[85] |
Normal Glc, Ins, TG & FFA[84] Normal Glc, ↑Ins, ↑TG & ↑FFA[85] |
Normal leptin[84] ↑Leptin & ↓Adiponectin[85] |
Normal liver TG[84] Steatosis[85] |
Yes[84,85] | Severely impaired HGP[84] Impaired HGP[85] |
|
Liver[86,87] (w/ Alb-Cre) |
Progressive obesity[86] Normal[87] |
↑Glc, ↑Ins, ↑TG[86] Normal Glc[87] |
↑Leptin & ↓Adiponectin[86] |
Normal liver TG[86,87] |
Yes[86] No[87] |
|
|
Pancreas[94] (w/ Insulin-Cre) |
Normal | Normal | ND | Normal liver TG | No | Pancreatic islet expansion on chow diet, but blunted response to high-fat diet |
|
Macrophage[96-98] (chimeras#,[96], w/ Mx- Cre*,[98]; Lyzs-Cre[97]) |
ND | ↓apoE, ↓LDL- cholesterol[98] |
ND | ND | ND | Increased atherosclerosis in recipients of PPARγ−/− macrophages[96,97] |
The different mouse models have various age and diet-dependent responses, thus for simplicity the above descriptions are for the adult phenotype in the postprandial state on a chow diet unless otherwise indicated. ND, not determined; Glc, glucose; Ins, insulin; TG, triglycerides; FFA, free fatty acids; Chol, cholesterol; MCK, muscle creatine kinase; HGP, hepatic glucose production; Alb, albumin; Mx, myxovirus resistance 1, interferon-inducible protein; Lyzs, lysozyme; apoE, apolipoprotein E; LDL, low density lipoprotein.
#
Derived from PPARγ−/− ES-cells, >90% of all macrophages PPARγ−/−.
*
The use of Mx-Cre also leads to PPARγ deficient liver.