Table 2.

Characteristics of included studies.

Study	Health Condition (n) Participants (Mean Age)	Study Design EG and/or CG	Therapeutic Intensity	Conclusion
Asghari et al., 2022 [33]	NAFLD (n = 60) CR (40.08 years) and CG (39.27 years)	A randomized controlled trial CR: healthy calorie-restricted diet CG: control	Healthy eating and weight control advice for12 weeks Participants in the CR group were targeted to lose a maximum of 10% of their baseline body weight through a healthy calorie-restricted diet	CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/antioxidative status in these patients.
Besse-Patin et al., 2014 [34]	Eleven obese (n = 11) Non-diabetic male subjects (35.4 years)	An interventional clinical trial Single arm: endurance training	8-week endurance training The 45–60 min exercise sessions consisted mainly of cycling and running, 5 times a week, for 8 weeks	Exercise training upregulates muscle apelin expression in obese subjects.
Campderrós et al., 2020 [26]	Healthy (n = 18) Marathon runners (41.71 years)	An interventional clinical trial Single arm: marathon	42.2-km running race Maintaining an adequate level of hydration during the race	GDF-15 and FGF-21 levels transiently increased in runners following a marathon race.
Dâmaso et al., 2021 [27]	Overweight and obese (n = 31) Overweight and obese women (32 years)	An interventional clinical trial Single arm: overweight and obese women	12-week interdisciplinary weight loss program Nutritional therapy (individual nutritional consultation), physical activity (weekly videos with examples of exercise and health education information), and education for lifestyle changes	Changes in FGF-21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels.
De la Torre-Saldaña et al., 2019 [28]	Healthy (n = 82) Young sedentary healthy women (23 years)	An interventional clinical trial Single arm: physical activity	Maintaining daily physical activity according to a regular diet, lifestyle, and instructions for 2 weeks	Serum irisin and FGF-21 levels significantly increased after 2 weeks of supervised physical activity.
Keihanian et al., 2019 [29]	Type 2 diabetes mellitus (n = 34) ATG (52.4 years), RTG (52.4 years), and CG (53.0 years)	A controlled clinical trial ATG: aerobic training RTG: resistance training CG: control	Aerobic training: 30–45 min of aerobic running at 65–75% of maximum heart rate for 8 weeks Resistance training: 8 weeks of three sets of 10 repetitions maximum of leg press, bench press, knee extension, seated cable row, knee flexion, military press, and calf rise.	Aerobic and resistance exercise training led to a significant decrease in serum fetuin-A and fetuin-B levels and increased FGF-21 levels in men with type 2 diabetes mellitus.
Matsui, et al., 2022 [32]	Overweight and obese (n = 14) Overweight and obese men (49 years)	An interventional clinical trial Single arm: aerobic exercise	Supervised aerobic exercise training for 12 weeks (three times per week) Aerobic exercise (walking and/or jogging) was performed with moderate intensity (Borg scale: 12–14) for approximately 40–60 min.	Lowering postprandial circulating FGF21 levels may be associated with the improved glucose tolerance induced by habitual aerobic exercise in overweight and obese men.
Shabkhiz et al., 2021 [30]	Elderly men with and without T2D (n = 44) Elderly men without T2D (72.08 years) and with T2D (72.45 years)	A randomized controlled clinical trial EG: resistance training without and with T2D CG: normal activity without and with T2D	Resistance training: machine-based exercises (leg press, leg extension, seated leg curl, seated calf, bench press, compound row, triceps press, and bicep curl) over 12 weeks/3 sessions per week.	12 weeks of RT induced an overall significant reduction of FGF-21 and myostatin in elderly men with and without T2D.
Takahashi et al., 2020 [31]	NAFLD (n = 50) EG (55.5 years) and CG (50.4 years)	A retrospective clinical study EG: resistance training CG: lifestyle counseling	Resistance training: three sets of push-ups and three sets of squats at 20–30 min per session 3 times a week for a total of 12 weeks.	Simple resistance exercise reduced CK-18 and FGF-21 levels in patients with NAFLD.
Taniguchi et al., 2016 [35]	Elderly men (n = 32) Elderly Japanese men (69.6 years)	A randomized crossover trial EG: endurance exercise CG: control	5-week endurance exercise program The exercise program comprised three cycle ergometer sessions per week. The exercise time was 30 min for weeks 1 and 2 and 45 min for weeks 3–5.	A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels.

ATG, aerobic training group; CG, control group; CK-18, cytokeratin 18; CR, calorie-restricted; EG, experimental group; FGF-21, fibroblast growth factor 21; GDF-15, growth differentiation factor 15; NAFLD, nonalcoholic fatty liver disease; RTG, resistance training group; T2D, type 2 diabetes mellitus.