Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review

Table 1 General characteristic of studies included

Ref.	Number of subjects with NAFLD	Age (mean)	Sex (male, %)	BMI (mean)	Primary measure	Exercise intervention	Dietary intervention	Program length	Session frequency (wk)	Exercise session duration (min)
Hallsworth et al[27], 2011	21	AE: 52	NR	AE: 32.3	H-MRS	RE	No	8 wk	3	45-60
		C: 62		C: 32.3
Sullivan et al[28], 2012	33	E: 49	AE: 33	AE: 37.1	H-MRS	AE	No	16 wk	5	30-60
		C: 48	C: 17	C: 40
Bacchi et al[29], 2013	40	AE: 56	AE: 71	AE: 30.5	H-MRS	AE and RE	No	4 mo	3	60
		RE: 56	RE: 71	RE: 28.8
Eckard et al[33], 2013	56	LFDE: 44	LFDE: 50	LFDE: 32.7	Liver biopsy	AE	Yes	6 mo	4-7	20-60
		MFDE: 55	MFDE: 67	MFDE: 40.3
		ME: 52	ME:67	ME: 31.3
		C: 51	C: 64	C: 34.7
Wong et al[12], 2013	154	AE: 51	AE: 52	AE: 51	H-MRS,	AE	Yes	12 mo	3-5	30
		C: 26	C: 41	C: 25.3	Fibroscan
Pugh et al[30], 2014	31	AE: 48	AE: 54	AE: 31	H-MRS	AE	No	16 wk	3	30-45
		C: 47	C: 50	C: 30
Cuthbertson et al[31], 2016	69	AE: 50	AE: 77	AE: 30.6	H-MRS	AE	No	16 wk	3-5	30-45
		C: 52	C: 80	C: 29.7
Hallsworth et al[32], 2015	29	AE: 54	NR	AE: 31	H-MRS	AE	No	12 wk	3	30-40
		C: 52		C: 31

AE: Aerobic exercise; RE: Resistance exercise; C: Control; LFDE: Low-fat diet plus moderate exercise; MFDE: Moderate-fat diet plus moderate exercise; ME: Moderate exercise; NR: Not reported; RT: Randomized trial; BMI: Body mass index; NAFLD: Non-alcoholic fatty liver disease; H-MRS: Hydrogen-magnetic resonance spectroscopy.

Table 2 Summary of responses in patients receiving exercise only compared to controls

Ref.	Number of subjects with NAFLD	Number of subjects who completed the study	Exercise group	Control group	Percentage of fat reduction in exercise group	Percentage of fat reduction in control group
Hallsworth et al[27], 2011	21	19	11	8	13%	3%
Sullivan et al[28], 2012	33	18	12	6	10%	-8%3
Bacchi et al[29], 2013 (Aerobic)1	40	31	14	-	33%	-
Bacchi et al[29], 2013 (Resistance)1	40	31	17	-	26%	-
Eckard et al[33], 20132	56	41	9	11	21%	8%
Pugh et al[30],2014	31	21	13	8	33%	16%
Cuthbertson et al[31], 2016	69	50	30	20	48%	9%
Hallsworth et al[32], 2015	29	25	14	11	26%	-1%3

¹Study with 2 different exercise limbs combined; one aerobic, one resistance;

²Study with 4 limbs one of which is exercise;

³Control groups in these studies had an increase in liver fat. NAFLD: Non-alcoholic fatty liver disease.

Table 3 Summary of responses in patients receiving diet and exercise compared to controls

Ref.	Number of subjects with NAFLD	Number of subjects who completed the study	Diet and exercise group	Control group	Percentage of fat reduction in exercise group	Percentage of fat reduction in control group
Eckard et al[33], 20131	56	41	9	11	27	8
Eckard et al[33], 20131	56	41	12	11	35	8
Wong et al[12], 2013	154	145	74	71	55	17

¹Study in which 1 limb had low-fat and other moderate-fat diet intake. NAFLD: Non-alcoholic fatty liver disease.

Table 4 Summary of studies included

Ref.	Intervention	Changes in fat	Physiologic changes	Clinical outcome	Exercise outcome
Hallsworth et al[27], 2011	RE	13% relative decrease in IHTG in exercise group	No significant change in blood lipids or ALT	No effect on body weight, visceral adipose tissue volume or whole body fat	RE without weight change is effective in reducing IHTG in people with NAFLD
			Approximately 12% increase in insulin sensitivity and increased fat oxidation
Sullivan et al[28], 2012	AE	10.3% ± 4.6% relative decrease in IHTG in exercise group	Plasma ALT decreased 12.8% + 3.1 in exercise group	Body weight, body fat mass remained same	Small decrease in IHTG content
Bacchi et al[29], 2013	AE and RE	Reduction in IHTG by 35.8% in AE vs 25.9% in RE	HbA1c, HDL, TG, insulin sensitivity improved	BMI, total body fat mass, VAT, SAT were reduced	Absolute and relative reduction in IHTG in both exercise groups
Eckard et al[33], 2013	Diet and AE	Significant change was found in pre to post NAFLD activity score	Significant decrease in Brunt grade, ALT, AST	No subgroup achieved a significant weight loss of > 5%	Lifestyle modification improved liver histology after 6 mo intervention
				Changes in % body fat were minimal	Weight loss is not the key to improving liver histology
Wong et al[12], 2013	Diet and AE	6.7% decrease in IHTG in intervention group	Decrease in Total cholesterol, LDL, ALT and liver stiffness	Reduction in body weight 5.6 kg, in BMI and waist circumference	64% of patients achieved remission of NAFLD in exercise group
Pugh et al[30], 2014	AE	IHTG decreased by 33% in exercise group SAT decreased no significant difference in VAT, total abdominal fat and muscle fat	Fasting glucose decreased No difference in HOMA score, insulin, liver enzymes, lipid profile, adiponectin, and leptin	No weight change Cardiorespiratory fitness improved Waist circumference decreased	improved endothelial dysfunction in the absence of change in liver fat and visceral fat content exercise training can reduce intrinsic CVD risk in NAFLD
Cuthbertson et al[31], 2016	AE	IHTG Significantly decreased (19.4%→10.1% in AE, 16%→14.6% in control)	No significant change in HOMA, plasma insulin, fetuin, irisin, adiponectin	Cardiorespiratory fitness improved in exercise group	Improvement in peripheral IR but not in hepatic IR
Hallsworth et al[32], 2015	AE	27% reduction in IHTG in exercise group	Decrease in ALT and AST Improvement in diastolic function	No weight change Mean 1.8 kg reduction in fat mass and body fat percentage	Significant reduction in IHTG, liver enzymes and body fat

H-MRS: Proton magnetic resonance spectroscopy; RE: resistance exercise; AE: Aerobic exercise; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; IR: Insulin resistance; HOMA: Homeostasis model assessment of insulin resistance; HbA1c: Glycosylated hemoglobin; HDL: High density lipoprotein; LDL: Low density lipoprotein; TG: Triglyceride; BMI: Body mass index; IHTG: Intrahepatic triglyceride.