Plasma concentrations of zonulin are elevated in obese men with fatty liver disease

Figures & data

Table 1 Clinical characteristics of the subjects

Characteristic	Normal (n=17)	Mild fatty liver (n=89)	Moderate-to-severe fatty liver (n=34)	P-value
Age, years	44.5±9.5	44.8±8.9	44.7±9.2	0.986
Systolic BP, mmHg	132.9±11.3	131.0±16.6	132.5±12.1	0.830
Diastolic BP, mmHg	82.3±8.6	81.9±11.4	84.8±11.4	0.433
Height, cm	173.8±8.4	174.3±6.5	174.9±4.8	0.838
Weight, kg	84.1±10.7	87.3±10.6	89.8±9.4	0.168
BMI, kg/m^2	27.8±2.5	28.8±2.8	29.3±2.6	0.161
WC, cm	96.3±4.8	97.2±6.5	97.5±6.0	0.806
Fasting glucose, mg/dL	98.6±13.9	101.4±16.4	100.0±23.9	0.818
HbA1c, g/dL	5.6±0.5	5.8±0.8	7.1±7.7	0.205
AST, U/L	25.5±11.4	26.1±14.5	27.9±17.6	0.802
ALT, U/L	30.0±15.2	37.2±20.6	38.7±27.9	0.391
GGT, U/L	65.5±55.1	62.0±84.4	58.9±48.0	0.954
TB, mg/dL	0.78±0.24	0.87±0.37	0.86±0.41	0.695
Total cholesterol, mg/dL	180.1±43.8	192.6±35.8	186.4±35.8	0.373
LDL-C, mg/dL	115.0±34.7	135.5±31.7	134.6 ± 32.2	0.055
HDL-C, mg/dL	49.0±9.1	47.0±8.9	42.9±9.2	0.035
Triglyceride, mg/dL	174.2±86.3	173.3±73.3	153.4±39.2	0.336
Serum creatinine, mg/dL	0.90±0.18	0.89±0.13	0.91±0.13	0.704
eGFR, mL/min/1.73m^2	95.6±23.1	95.3±14.5	91.1±25.0	0.513
Zonulin, ng/mLa	0.618±1.15	2.143±4.27	5.815±3.11	<0.001
Smoking status				0.466
Nonsmoker	2 (11.8)	16 (18.0)	10 (29.4)
Former smoker	9 (52.9)	38 (42.7)	11 (32.4)
Current smoker	6 (35.3)	35 (32.4)	13 (38.2)
Alcohol consumption				0.476
None	1 (5.9)	9 (10.1)	7 (20.6)
Social	9 (52.9)	35 (39.3)	7 (20.6)
Heavy	6 (35.3)	32 (36.0)	11 (32.4)
Binge	1 (5.9)	13 (14.6)	9 (26.5)
Physical activity
Inactive	8 (47.1)	48 (53.9)	15 (44.1)
Active	9 (52.9)	41 (46.1)	19 (55.9)	0.591
Medical history
Hypertension	6 (35.3)	21 (23.6)	8 (23.5)	0.579
Diabetes	2 (11.8)	7 (7.9)	2 (5.9)	0.763
Dyslipidemia	2 (11.8)	5 (5.6)	2 (5.9)	0.632

Notes: All values are presented as mean±SD or number (%). P-values were calculated using the chi-square test for discrete outcomes and one-way ANOVA for continuous outcomes.

a There was a significant trend toward increased mean values of concentrations (P-trend<0.001).

Abbreviations: BP, blood pressure; BMI, body mass index; WC, waist circumference; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gammaglutamyltransferase; TB, total bilirubin; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; ANOVA, analysis of variance.

Table 2 Effect of plasma zonulin concentrations on the risk of fatty liver disease

	Mild fatty liver		Moderate-to-severe fatty liver
	OR (95% CI)	P-value	OR (95% CI)	P-value
Model 1a	1.51 (0.99–2.30)	0.059	1.90 (1.23–2.92)	0.004
Model 2b	1.44 (0.94–2.22)	0.095	1.83 (1.18–2.84)	0.007
Model 3c	1.40 (0.91–2.16)	0.122	1.77 (1.13–2.76)	0.015

Notes:

a Unadjusted model.

b Adjusted for HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and BMI.

c Adjusted for the covariates in Model 2 as well as age, smoking, alcohol consumption, physical activity, diabetes, and dyslipidemia.

Abbreviations: OR, odds ratio; BMI, body mass index.

Table 3 Median concentration of plasma zonulin according to fatty liver severity in the subgroups

Appropriate drinking subgroup
Normal (n=10)	Mild fatty liver (n=44)	Moderate-to-severe fatty liver (n=14)	P-value	P-trend
0.002 (0.001–0.687)	0.500 (0.002–2.250)	6.550 (3.150–8.050)	<0.001	0.002
Hazardous drinking subgroup
Normal (n=7)	Mild fatty liver (n=45)	Moderate-to-severe fatty liver (n=20)	P-value	P-trend
0.002 (0.001–2.000)	0.590 (0.003–2.750)	5.800 (3.450–7.775)	<0.001	0.001

Notes: All values are presented as median (interquartile range). P-values were calculated using the Kruskal–Wallis test.

Figure 1 OR of zonulin concentration in fatty liver disease in the appropriate drinking subgroup.

Notes: In the multivariate multinomial logistic regression analysis adjusted for covariates, the OR of zonulin concentrations in relation to the incidence of mild fatty liver was 1.63 (adjusted OR=1.63, 95% CI=0.75–3.55) in the appropriate drinking group and was not statistically significant. However, the OR for moderate-to-severe fatty liver was 1.91 (95% CI=1.01–3.95) in the same group and was statistically significant.
Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 2 OR of zonulin concentration in fatty liver disease in the hazardous drinking subgroup.

Notes: In the multivariate multinomial logistic regression analysis adjusted for covariates, the OR of zonulin concentrations in relation to the incidence of mild fatty liver was 1.17 (95% CI=0.69–1.96) in the hazardous drinking group and was not statistically significant. However, the OR for moderate-to-severe fatty liver was 1.56 (95% CI=1.02–2.67) in the same group and was statistically significant.
Abbreviation: OR, odds ratio.