Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models

Figures

• 

  Figure 1. Structure and specific forms of human chemerin. The initial preprochemerin and its different products are processed by different proteases related to inflammation. The signal peptide (purple) is cleaved prior to secretion. Then, the C-terminus is cleaved by different proteases giving several active isoforms such as chemerin F156, chemerin S157 and chemerin K158.

• 

  Figure 2. Structure and specific forms of human visfatin. Human visfatin can be found under the intra-cellular form of nicotinamide phosphoribosyltransferase (iNAMPT) having an enzymatic role to produce NAD+ (nicotinamide adenine dinucleotide), and under the extracellular form (eNAMPT) with the same role. Visfatin acts also as a cytokine that could act on target cells. NAMPT catalyzes the reaction between nicotinamide and 5-phosphoribosyl-1-pyrophosphate (PRPP) to yield nicotinamide mononucleotide (NMN), an intermediate in the biosynthesis of NAD+.

• 

  Figure 3. Structure and specific forms of human resistin. Human resistin is composed by a signal peptide (purple), a variable region (green) and a C-terminal domain. Resistin can be found under the monomeric form and can form dimeric and trimeric proteins thanks to disulfide bridges. Then, disulfide and non-disulfide bridges can be involved in the formation of the hexameric protein.

• 

  Figure 4. Structure and specific forms of human apelin. Human apelin is first of all found under the preproapelin form (77 amino acids) that will be cleaved by endopeptidases acting on basic amino-acid-rich regions giving the proapelin (55 amino-acids) and then the other tissue-dependent active isoforms (36, 17, 13 and Pyr-13 amino-acids). PCSK3 (proprotein convertase subtilisin/kexin 3) is involved in the cleavage of proapelin to apelin-13.

• 

  Figure 5. Receptors used by chemerin, visfatin, resistin and apelin for their signaling pathways. chemerin can bind three different receptors that are CMKLR1, GPR1 and CCRL2. CMKLR1 and GPR1 are coupled with intracellular Gαi proteins. The last receptor doesn’t have any active signaling pathway identified until now suggesting a putative role of co-receptor for CCRL2. Apelin has its own receptor called APJ coupled with intracellular Gq and Gαi proteins. Resistin could bind receptors such as CAP-1, ROR-1 and TLR-4 but it has to be confirmed. No receptor for visfatin has been identified until now.

• 

  Figure 6. Expression and effects on GnRH (Gonadotropin-Releasing Hormone) release of chemerin, visfatin, resistin and apelin in hypothalamus. ⇧ Increase/stimulation. ⇩ Decrease/inhibition. ND: not determined. CSF: cerebrospinal fluid.

• 

  Figure 7. Expression and effects on gonadotropic cells of chemerin, visfatin, resistin and apelin in pituitary. ⇧ Increase/stimulation. ⇩ Decrease/inhibition. ND: not determined.

• 

  Figure 8. Expression and effects of chemerin, visfatin, resistin and apelin on the ovarian follicle. ⇧ Increase/stimulation. ⇩ Decrease/inhibition.

• 

  Figure 9. Effects of chemerin, visfatin, resistin and apelin on steroidogenesis in vitro in primary human granulosa cells. Chemerin and resistin are known to inhibit IGF-1 (Insulin Like Growth Factor 1)-induced steroidogenesis whereas visfatin and apelin exert stimulatory effects.

• 

  Figure 10. Expression and effects of chemerin, visfatin, resistin and apelin on testicular function. ⇧ Increase/stimulation. ⇩ Decrease/inhibition.

• 

  Figure 11. Effects of chemerin, visfatin, resistin and apelin on ovarian physiology, plasma and adipose tissue in polycystic ovarian syndrome (PCOS) as compared to control patients. ⇧ Increase/stimulation. ⇩ Decrease/inhibition.

• 

  Figure 12. Description of PCOS syndrome and possible involvement of chemerin, visfatin, resistin and apelin in this syndrome.