Table 1: Comparison of PPAR expression and function between rodents and humans.


rodents humans

expression PPARα: liver (PPARα expression is subject to negative and positive regulation by insulin and glucocorticoids) [89, 90], adipose tissue (highly expressed in comparison to human, high levels of PPARα mRNA are detected in brown fat), heart, kidney, skeletal muscle, GI tract (mucosa of stomach and duodenum), transient expression in the developing central nervous system and during skin maturation [91, 93]
PPARδ: ubiquitously expressed (often at higher levels than PPARα and PPARγ), most expressed isotype in the adult nervous system [92, 93, 93], weakly expressed in liver, as compared with other tissues such as lung and kidney [91, 93, 96], skeletal and cardiac muscle, testis (very high in sertoli cells) [93], expression is markedly induced in the uterus at the time of blastocyte implantation and remains abundantly expressed in the decidua at the postimplantation stage [97]
PPARγ: white and brown adipose tissues (major sites of expression) [98], intestinal mucosa (high levels in colon and caecum but less in the small intestine) [99, 100], lymphoid tissues (spleen and Peyer's patches) [93, 94], in retina and skeletal muscle (at low levels)
PPARα: liver (its levels in the liver appear lower than in the rodent liver) [101], adipose tissue, heart, skeletal muscle, intestine, renal cortex and kidney [102]
PPARδ: ubiquitously expressed (moderate levels in all tissues), highest expression rates are found in small intestine, colon, heart, adipose tissue, inflammatory cells, skin, brain and placenta [102]
PPARγ: adipose tissue and immune cells (in contrast to rodent, no expression in spleen or lymphoid tissues) [103]
function PPARs promote peroxisome proliferation in contrast to human PPARs leading to carcinogenic potential especially in liver [82]. Species specificity in ligand recognition (may be linked to the speed of evolution of the PPAR genes) [104]
PPARα: well conserved across species [91, 105], functions in rodents and human are similar and homology of the DBD and LBD is high [91, 107, 108]. Peroxisome proliferation leads to an increase in the density of peroxisomes and peroxisomal fatty acid β-oxidation, but PPARα agonists not only play a role in induction of genes for fatty acid oxidation, but also are carcinogenic in liver (specific to rats and mice) [109].
PPARδ: PPARδ shows species variations in structure and ligand activation profiles [91, 105]
PPARγ: well conserved across species [91, 105], but the PPARγ motif in E5 in the mouse genome was located in a small (∼100bp) fragment of a rodent-specific LINE/L1 transposon species-specific PPRE [110]
PPARα: regulates multiple metabolic processes including β-oxidation, lipid transport and gluconeogenesis and is also involved in inflammatory processes in summary regardless of the species, the expression of PPARα correlates with high mitochondrial and peroxisomal oxidation activities [104], however, there is a marked decrease in PPARα expression of human hepatocytes in the presence of an agonist due to differences in the promoter response elements of target genes [111], An inactive PPARα splice variant was found exclusively in human liver samples [101]
PPARδ: regulation of fatty acid β-oxidation in skeletal muscle
PPARγ: major impact on adipocyte differentiation and lipid metabolism, two putative enhancers/PPREs in hASCs (not in the murine genome) [110] the orthologous CD36 loci revealed multiple species-specific regulatory elements [110]