Prolylcarboxypeptidase (PRCP) as a new target for obesity treatment

Figures & data

Figure 1 The physiological action of prolylcarboxypeptidase (PRCP).

Notes: PRCP elicits increased production of proinflammatory prostaglandins and vasodilatory nitric oxide and promotes orexigenic action through inactivation of α-MSH.
Abbreviations: α-MSH, α-melanocyte-stimulating hormone; HK high molecular weight kininogen; PK, prekallikrein.

Figure 2 The role of the hypothalamus in food intake and metabolism.

Notes: The catalysis of α-MSH_1–13 to α-MSH_1–12 by PRCP leads to increased food intake and body weight gain in humans. Blue arrows indicate anorectic response and red arrows indicate orexigenic response.
Abbreviations: Act-α-MSH, acetylated α-MSH; AgRP, Agouti-related protein; ARC, arcuate nucleus of the hypothalamus; Des-α-MSH, desacetyl α-MSH; DM, dorsomedial hypothalamus; GABA, gamma-aminobutryric acid; LH, lateral hypothalamus; MC3R, melanocortin-3 receptor; MC4R, melanocortin-4 receptor; NPY, neuropetide y; POMC, pro-opiomelanocortin; PVN, paraventricular nucleus.

Figure 3 Schematic structure of pro-opiomelanocortin (POMC) and location of melanocyte-stimulating hormones (MSH).

Abbreviations: ACTH, adrenocorticotropic hormone; β-LPH, beta-lipotropic hormone; S, signal sequence; γ-MSH, gamma-MSH; α-MSH, alpha-MSH; β-MSH, beta-MSH; β-endorphin, beta-endorphin.

Figure 4 PRCP inhibitors provoke accumulation of α-MSH_1–13 peptide leading to reduced body weight, inflammation, and pain.

Abbreviations: α-MSH_1–13, a proopiomelanocortin (POMC) cleavage product; MC4R, melanocortin-4 receptor; MC1R, melanocortin-1 receptor; predominant receptors of α-MSH_1–13; AgRP, agouti-related protein; endogenous MC4R antagonist; MTII, MC4R agonist; and prolylcarboxypeptidase (PRCP), endogenous inactivator of α-MSH_1–13.