Peroxisome proliferator-activated receptor

In the field of

• α (alpha) - expressed in liver, kidney, heart, muscle, adipose tissue, and others^[6]
• β/δ (beta/delta) - expressed in many tissues, especially in brain, adipose tissue, and skin
• γ (gamma) - although transcribed by the same gene, this PPAR, by way of alternative splicing, is expressed in three forms:
  • γ1 - expressed in virtually all tissues, including
    colon, kidney, pancreas, and spleen
  • γ2 - expressed mainly in adipose tissue; it is 30 amino acids longer than γ1
  • γ3 - expressed in
    large intestine, white adipose tissue

These agents, pharmacologically related to the fibrates were discovered in the early 1980s.

PPARs were originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells in 1992.^[7] The first PPAR (PPARα) was discovered in 1990 during the search for a molecular target of a group of agents then referred to as peroxisome proliferators, as they increased peroxisomal numbers in rodent liver tissue, apart from improving insulin sensitivity.^[8]

When it turned out that PPARs played a much more versatile role in biology, the agents were in turn termed PPAR ligands. The best-known PPAR ligands are the thiazolidinediones.

After PPARδ (delta) was identified in humans in 1992,^[9] it turned out to be closely related to PPARβ (beta), previously described during the same year in an amphibian, Xenopus. The term "PPARδ" is generally used in the US, whereas the use of "PPARβ" has remained in Europe, where this receptor was initially discovered in Xenopus.

PPARs were so-named because they were discovered to induce peroxisome proliferation in rodents, but this induction of peroxisome proliferation is not believed to occur in humans.^[10][11]

Physiological function

All PPARs

The three main forms of PPAR are transcribed from different genes:

• PPARα - chromosome 22q12-13.1 (OMIM 170998)
• PPARβ/δ - chromosome 6p21.2-21.1 (OMIM 600409)
• PPARγ - chromosome 3p25 (OMIM 601487
  ).

• (A/B) - N-terminal region
• (C) DBD - DNA-binding domain
• (D) - flexible
  hinge
  region
• (E) LBD -
  ligand binding domain
• (F) C-terminal region

The DBD contains two

The LBD has an extensive

PPARα and PPARγ are the molecular targets of a number of marketed drugs.

For instance the

The synthetic chemical perfluorooctanoic acid activates PPARα while perfluorononanoic acid activates both PPARα and PPARγ. ^{[citation needed]}

Berberine inactivates PPARγ. ^{[citation needed]}

Other natural compounds from different chemical classes activate or inactivate PPARγ.^[21][22][23]

See also

• Metabolic syndrome
• Endocannabinoid system

References