Table 5.

In vivo exercise studies investigating exerkine receptor signaling and examples of further human tissues with exerkine receptor expression

Exerkine	Exerkine receptor	Refs	Examples of further human tissues expressing exerkine receptors
Skeletal muscle
NTN	GFRA2/ RET	146	GFRA2: Nervous system, bone morrow, CSF RET: PBMCs
TGF-β2	TGF-βR2	151	PBMCs, breast
IL-15	IL-15Rα	149	No data
Fractalkine	CX3CR1	145,150	Adrenal gland, PBMCs, liver, lungs
Musclin	NPR3	95	Blood, urine
Apelin	APLNR	147,152	Spinal chord
Cardiac muscle
BDNF	NTRK2	171	CNS, CSF, PBMCs
IL-6	IL6R	225	Blood, nasal respiratory epithelium
VEGF	VEGFR3	170	Blood, breast, placenta, cardiac muscle
NRG1	ERBB2, ERBB4	176	ERBB2: lung, skin ERBB4: skin
White adipose tissue
KYNA	GPR35	185	Blood, monocytes, neutrophils, CSF, cardiac muscle
FGF21	FGFR1/KLB	192	FGFR1: Blood, monocytes, neutrophils, CSF, cardiac muscle KLB: no data
Irisin	αV/β5 integrins	183	Integrin αV: immune cells, platelets, lymphatic tissue, fetal heart, bone marrow, bone, smooth muscle organs, lung, pancreas, prostate, reproductive organs Integrin β5: immune cells, lymphatic tissue, cerebral cortex, heart, oral epithelium, fetal gut, liver, spleen, lung, pancreas, placenta, uterus, cervix, ovary
Lactate	HCAR1	462,463	No data
IL-6	IL6R	225	Blood, nasal respiratory epithelium
FSTL1	DIP2A	32	No data
Bone
Irisin	αV/β5 integrins	183	See above
L-BAIBA	MRGPRD	57,194,476	Heart
RCN2	NRP2/1 integrin	124	Blood, CNS, smooth muscle organs, adipocytes, amniocyte, breast, urine, skin, placenta, fetal organs
Central nervous system
Lactate	HCAR1	200,201,215	No data
ANGPT1	TIE-2	202	Fetal heart, lung, placenta
GDF15	GFRAL/ RET	203,477	GFRAL: no data RET: PBMCs
Immune cells
IL-8	IL8R	232	Nasal respiratory epithelium, PBMCs, monocytes
IL-6	IL6R	224	Blood, nasal respiratory epithelium
Succinate	SUCNR1	51,52	No data
Skin
IL-15	IL-15Rα	144	No data
Liver
FN1	αV/β1 integrins	250	Integrin αV: see above Integrin β1: blood, immune cells, platelets, lymphatic tissue, bone marrow, bone, CNS, retina, heart, smooth muscle organs, kidney, spleen, lung, adipocytes, secretory glands, prostate, skin, reproductive organs

The exerkines displayed in this table are derived from in vivo exercise studies on exerkines and exerkine receptors. Estimated protein expression was extracted from the Human Gene Database (https://www.genecards.org). By using a cutoff of 0.5 parts per million (ppm) on a base-10 log scale, we present an experimentally sound collection of target tissues that are characterized by exerkine receptor expression and therefore have the potential to transduce the signals of exerkines into tissue adaption. Of note, some of the exerkine receptors listed in the table did not meet the described criteria for inclusion as target tissue (marked with “No data”). However, this does not rule out the possibility that convincing evidence for exerkine receptor expression might originate from individual investigations APLNR apelin receptor, CX3XR1 C-X3-C motif chemokine receptor 1, IL-15Rα Interleukin-15 receptor α, IL-15 Interleukin 15, TGF-βR2 transforming growth factor β receptor 2, GFRA2 glial cell line derived neurotrophic factor family receptor α 2, RET REarranged during Transfection, NTN neurturin, TRKB tropomyosin-related kinase B, BDNF brain-derived neurotrophic factor, NRG1 neuregulin 1, IL-6 Interleukin 6, IL-R Interleukin 6 receptor, IL-8 Interleukin 8, IL-8R Interleukin 8 receptor, ERBB2/ERBB4 Erb-B2 receptor tyrosine kinase 2/Erb-B2 receptor tyrosine kinase 4, VEGFR3 vascular endothelial growth factor receptor 3, VEGF vascular endothelial growth factor, NRP2 neuropilin 2, RCN2 reticulocalbin 2, FSTL1 follistatin-like 1, DIP2A disco-interacting protein 2 homolog A, MRGPRD Mas-related G protein-coupled receptor type D, L-BAIBA β-aminoisobutyric acid, HCAR1 hydroxycarboxylic acid receptor 1, FGFR1 fibroblast growth factor receptor 1, KLB co-receptor β-Klotho, FGF21 fibroblast growth factor 21, GPR35 G protein-coupled receptor 35, KYNA kynurenic acid, GFRAL glial cell line derived neurotrophic factor family Receptor a Like, GDF15 growth differentiation factor 15, TIE-2 tyrosine-protein kinase receptor TEK, ANGPT1 angiopoietin 1, SUCNR1 succinate receptor 1, PBMC peripheral blood mononuclear cells, CSF cerebrospinal fluid, CNS central nervous system