Table 1.

Summary of myokine studies: effects of exercise training

Study	Subjects/animals	Intervention	Tissue examined	Main findings
Irisin
Bostrom et al., 1995	Muscle creatine kinase promoter (MCK)‐PGC1‐α transgenic and wild type BALB/c mice	3 weeks of swimming	–	Increase of brown‐like genes on the WAT
			Epididymal fat	Twofold increase in Ucp1 mRNA
			Subcutaneous inguinal	65‐fold increase in Ucp1 mRNA
		3 weeks of wheel running	Visceral, epididymal	Twofold increase in Ucp1 mRNA
			Subcutaneous inguinal	25‐fold increase in Ucp1 mRNA
			Brown adipose tissue	Increase whole‐body energy expenditure
	Non‐diabetic men	10 weeks of endurance training at ~65% of VO2max	Muscle biopsies	FNDC5, VEGFB and TIMP4, LRG1 and mRNAs
			Blood	Circulating Irisin
	BALB/c mice, primary adipocytes	Incubation with FNDC5	Cell culture	7 to 500‐fold increase of Ucp1; threefold in PPARγ mRNA
Kim et al., 2013	Lean and overweight/obese adults	8 weeks of resistance training at 65–80% of 1RM	Blood	~17.5% irisin plasma levels
		8 weeks of endurance training at 65–80% of HRmax		body fat and BMI
Huh et al., 2005	Young males(± 20 years)	8 weeks or 30 min of endurance training	Blood	~18% circulating irisin
Metrnl
Rao et al., 2010	Young men	RT at 80% 1RM + 30 min of cycling at 70% VO2peak	Vastus lateralis muscle biopsies	metrnl up to 4 h post exercise. mRNA peak expression was at 1 h
	Wild‐type C57/BL6J, BALB/cJ Myo‐PGC‐1α4, ΔdbGATA mice, metrnl KO mice		Subcutaneous fat; epididymal fat;	M2‐macrophages gene markers; inflammation genes in the AT (TNF‐α, IFN‐γ and IL‐1β)
		60 min of downhill running exercise at 15 m·min−1		Thermogenesis; mitochondrial gene programme; UCP‐1 (~3.5), DIO2, PGC‐1α, ERR‐α mRNA
			Brown adipose tissue	metrnl mRNA and thermogenic gene programme; UCP‐1 mRNA in BAT
			Quadriceps and triceps muscle	~fourfold increase of metrnl mRNA
			Blood	~twofold increase in circulating metrnl
		Adenovirus injection to deliver full‐length metrnl to the liver	Liver and blood	~20‐fold increase in liver mRNA and ~five to sixfold in plasma
			Culture of myotubes PGC‐1α4 expression	~eightfold increase of metrnl mRNA
Fibroblast growth factor 21
Cuevas‐Ramos et al., 2009	Sedentary young women	2 weeks of endurance exercise at 85% of HR	Blood	~66% circulating levels of FGF‐21; ~25% triglycerides; Epinephrine; FFA (~50%)
Tanimura et al., 2015	Male ICR mice	60 min of endurance exercise at 10–30 m·min−1	Liver	mRNA and protein levels of FGF‐21
			Blood	Serum FGF‐21
			Gastrocnemius muscle	mRNA and protein of FGF‐21; p‐Akt/Akt protein
	Young sedentary men	Single bout for 60 min at 75% of VO2max	Blood	Serum FGF‐21, NEFA, 3‐hydroxybutyric acid
Kim et al., 2015	Male C57/BL6 mice	30 min of endurance exercise at 25 m·min−1	Blood	FGF‐21 serum levels
		30 min of endurance exercise at 50 or 80% of VO2max	Liver	FGF‐21, PPARα, ATF4 mRNA
	Male adults		Blood	FGF‐21 serum levels only 1 h after end of bout
Slusher et al., 2016	Obese and lean adults	30 min of endurance training at 75% of VO2max	Blood	FGF‐21 in lean subjects regardles the time and in the obese only after 1 h post bout
				Increased circulatory FGF‐21 correlates to total relative energy expenditure
Hansen et al., 2016	Young lean and type 2 diabetic men	2 h of endurance exercise at 60% of VO2max + Patients that underwent through pancreatic clamp	Blood	Glucagon/Insulin ratio; Plasma FGF‐21 in controls;
				In type 2 diabetic patients and Pancreatic clamp FGF‐21 is abolished in plasma
IL‐15
Kim et al., 2015	Male Zucker diabetic fatty rats	12 weeks – 60 min of endurance training at 15–20 m·min−1	Soleus and gastrocnemius muscles	IL‐15 protein levels in S. muscle
Bazgir et al., 2015e	Young male non‐ and athletes	Two bouts of RT, one focusing on CON at 70–80% 1RM and the second on ECC at 90–100% 1RM ‐with 8 to 10 repetitions	Blood	IL‐15 serum levels
				hs‐CRP levels in athletes
				hs‐CRP and TNF‐α levels in non‐athletes
Quinn et al., 2015	IL‐15‐KO and IL‐15Rα KO mice	Endurance training at 15‐17 m·min−1 until exhaustion	Gastrocnemius muscle	Endurance capacity in KO mice; MHC mRNA
				IL‐15 mRNA in G. muscle; Serum IL‐15 in KO mice
				PPARδ and SIRT1 mRNA and protein after IL‐15 injection and 3 h post bout
		Acute injection of IL‐15	Blood	IL‐15Rα in Control and KO‐mice
				IL‐15 circulating levels in IL‐15Rα‐KO mice
				PGC‐1α and 1β in SKM of IL‐15KO
				IL15Rα after an acute bout of exercise
Pistilli et al., 2008	IL‐15Rα KO mice	14 h data from Voluntary wheel exercise	EDL, gastrocnemius and quadriceps muscle	Ambulatory activity, fatigue resistance and wheel revolutions
				IL‐15 mRNA in muscles of IL‐15Rα‐KO mice IL‐15, Ppard, Pgc‐1α, citrate synthase, SERCAII and calsequestrin mRNA in EDL and gastrocnemius of IL‐15Rα‐KO mice
IL‐6
McGinnis et al., 2015	C57/Bl6 or IL‐6−/− mice	3 days of 60 min of treadmill exercise at 18 m·min−1 prior I/R surgery procedure	Serum	~4.5‐fold in IL‐6 and sIL‐6R serum concentration after 30 min exercise in controls; IL‐6R in G. muscle and heart after exercise in C57/Bl6 mice
			Gastrocnemius muscle	COX‐2 mRNA and protein post exercise; iNOS and p‐STAT protein before and after exercise in IL‐6−/− in G. muscle
				of ~65% of necrotic area, ECG score protection against arrhythmias in C57/Bl6
			Heart	p‐p44/42 MAPK and p‐p38 MAPK proteins in the myocardium after the exercise in C57/Bl6 mice