Table 1.
Loss-of-function studies on PPARγ cofactors in adipogenesis and energy metabolism
PPARγ cofactor | Phenotype in the absence of the cofactor | |
| ||
Cell-based studies | Mouse studies | |
| ||
Brg1, hBrm (SWI/SNF components) | Blocked adipogenesis (Salma et al. [25]) | — |
Reduced presence of Pol II and GTFs on the promoter (Salma et al. [25]) | ||
Decreased PPARγ transcription (Salma et al. [25]) | ||
| ||
TIF2 | Increased lipolysis (Picard et al. [50]) | Enhanced adaptive thermogenesis (Picard et al. [50]) |
Protection against obesity (Picard et al. [50]) | ||
Increased insulin-sensitivity (Picard et al. [50]) | ||
Improved metabolic profile. Increased lipolysis (Picard et al. [50]) | ||
Decreased presence of PPARγ | ||
| ||
SRC-1 | — | Predisposition to obesity (Picard et al. [50]) |
Reduced energy expenditure (Picard et al. [50]) | ||
Reduced fatty acid oxidation in brown adipose tissue (Picard et al. [50]) | ||
Decreased energy expenditure, attenuated fatty acid oxidation (Picard et al. [50]) | ||
| ||
SRC-1/pCIP double knockout | Abrogated preadipocyte differentiation (Wang et al. [51]) | Diminished lipid storage in brown fat; increased caloric intake on both chow and high-fat diet due to increased leptin levels; resistance to diet-induced obesity; increased basal metabolic rate and energy expenditure (Wang et al. [51]) |
Reduced expression of PPARγ-target genes, including UCP-1, due to corepressor recruitment and decreased PPARγ recognition of PPREs (Wang et al. [51]) | ||
| ||
PGC-1α | Impaired induction of thermogenic genes in BAT (Uldry et al. [52]) | Reduced mitochFondrial function (Lin et al. [53]) |
Decreased number and impaired function of mitochondria (Uldry et al. [52]) | Resistance to obesity and hyperactivity (Lin et al. [53]) | |
| ||
TRAP220/DRIP205/PBP | Defective PPARγ-stimulated adipogenesis (Ge et al. [31]) | Defective vascular development similar to that seen in PPARγ-null mice (Barak et al. [54]; Zhu et al. [55]) |
| ||
PRIP/NRC/RAP250/TRBP | Decreased PPARγ-mediated transcriptional activation (Antonson et al. [56]; Zhu et al. [57]) | — |
| ||
RIP140 | Upregulation of genes involved in energy dissipation (Poweka et al., 2006) | Increased oxygen consumption and resistance to high-fat diet-induced obesity (Leonardsson et al. [58]) |
Increased PGC-1α expression (Poweka et al., 2006) | Expression of lipgenic enzymes is decreased. UCP-1 (involved in energy dissipation in BAT) expression is increased (Leonardsson et al. [58]) | |
| ||
NCoR and SMRT | Increased adipocyte differentiation (Yu et al. [42]) | — |
| ||
Sirt1 | Decreased NCoR levels (Picard et al. [43]) | — |