General Characteristics and Serum Maresin-1 Levels of Study Participants
A total of 116 non-NAFLD subjects and 124 NAFLD patients were enrolled in this study. The average age of the subjects was 43.44 ± 11.36 years, including 134 males (55.8%) and 106 females (44.2%). Table 1 summarizes the general anthropometric, biochemical and clinical parameters and serum Maresin-1 levels of the subjects. Compared to non-NAFLD subjects, NAFLD patients had higher BMI, WC, HC, WHR, SBP, DBP, FBG, WBC count, ALT, AST, GGT, ALP, Urea, UA, Crea, TC, TG, LDL-C, and HCY (P < 0.05 or P < 0.01 or P < 0.001) and lower levels of AST/ALT and HDL-C (both P < 0.001). The proportion of male was higher in subjects with NAFLD than in those non-NAFLD (P = 0.029). No significant differences were found in age, neutrophil count, TP, ALB, GLO, and A/G.
Table 1
Main clinical parameters and serum Maresin-1 levels in all participants.
Variables | non-NAFLD | NAFLD | P-value |
Male/Female | 57/59 | 77/47 | 0.029 |
Age (year) | 41.50 (33.00–51.00) | 45.50 (35.00–53.00) | 0.286 |
BMI (kg/m2) | 22.54 (21.20–24.20) | 27.26 (25.48–29.49) | 0.000 |
WC (cm) | 79.68 ± 8.52 | 90.39 ± 7.92 | 0.000 |
HC (cm) | 95.00 (91.00–98.00) | 100.00 (96.00-104.75) | 0.000 |
WHR | 0.84 ± 0.06 | 0.89 ± 0.05 | 0.000 |
SBP (mmHg) | 118.00 (110.00-124.00) | 130.50 (119.00-138.00) | 0.000 |
DBP (mmHg) | 71.45 ± 9.21 | 77.29 ± 10.68 | 0.000 |
FBG (mmol/L) | 4.95 (4.68–5.23) | 5.32 (4.90–5.75) | 0.000 |
WBC (*10^9/L) | 6.11 ± 1.22 | 6.75 ± 1.35 | 0.000 |
NEU (*10^9/L) | 3.65 ± 0.92 | 3.85 ± 0.95 | 0.099 |
ALT (U/L) | 18.20 (13.30–27.20) | 27.90 (21.25–42.05) | 0.000 |
AST (U/L) | 20.20 (17.30-26.05) | 23.40 (19.43–27.50) | 0.002 |
AST/ALT | 1.15 (0.92–1.34) | 0.83 (0.66–0.99) | 0.000 |
TP (g/L) | 73.00 ± 3.01 | 72.63 ± 2.93 | 0.328 |
ALB (g/L) | 46.25 (45.00-47.63) | 46.05 (45.03–47.80) | 0.970 |
GLO (g/L) | 26.62 ± 2.52 | 26.25 ± 2.59 | 0.260 |
A/G | 1.76 (1.62–1.90) | 1.77 (1.65–1.91) | 0.501 |
GGT (U/L) | 16.05 (13.10-26.85) | 31.55 (20.58–48.60) | 0.000 |
ALP (U/L) | 67.40 (53.95–79.78) | 74.05 (62.55–88.05) | 0.003 |
Urea (mol/L) | 4.70 (3.90–5.63) | 5.13 (4.59–5.93) | 0.004 |
UA (µmol/L) | 320.00 (261.48-380.78) | 370.15 (316.65–440.00) | 0.000 |
Crea (µmol/L) | 63.35 (53.80–71.40) | 70.50 (55.75–77.23) | 0.006 |
TC (mmol/L) | 4.73 ± 0.77 | 4.95 ± 0.72 | 0.022 |
TG (mmol/L) | 1.16 (0.84–1.67) | 2.00 (1.42–2.67) | 0.000 |
HDL-C (mmol/L) | 1.35 (1.17–1.66) | 1.08 (0.96–1.22) | 0.000 |
LDL-C (mmol/L) | 3.10 ± 0.83 | 3.42 ± 0.70 | 0.002 |
HCY (µmol/L) | 9.55 (8.00-11.50) | 10.65 (8.80–12.10) | 0.009 |
Maresin-1 (pg/mL) | 73.11 (65.12–84.50) | 63.63 (59.87–73.93) | 0.000 |
Continuous variables are mean ± standard deviation (SD) or medians (25th, 75th percentiles). NAFLD: non-alcoholic fatty liver disease, BMI: body mass index, WC: waist circumference, HC: hip circumference, WHR: waist to hip ratio, SBP: systolic blood pressure, DBP: diastolic blood pressure, FBG: fasting blood glucose, WBC: white blood cells, NEU: neutrophil, ALT: alanine aminotransferase, AST: aspartate aminotransferase, TP: total protein, ALB: albumin, GLO: globulin, A/G: Albumin-globulin-ratio, GGT: gamma-glutamyl transpeptidase, ALP: alkaline phosphatase, UA: uric acid, Crea: creatinine, TC: total cholesterol, TG: triglyceride, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, HCY: Homocysteine. |
In all study subjects, the distribution of serum Maresin-1 concentration was from 51.65-224.45 pg/mL. There was no significant difference in circulating Maresin-1 levels between men and women (66.99 [61.18–77.40] vs 71.52 [62.57–79.32], P = 0.078). In addition, in order to understand the serum levels of Maresin-1 under different metabolic conditions, all participants were divided into normal and abnormal groups according to the levels of FBG, lipids or BMI [19, 20]. As shown in Fig. 1, serum Maresin-1 levels were significantly lower in subjects with elevated FBG, TC and TG levels (all P < 0.001, Fig. 1A-C), decreased HDL-C levels (P < 0.001; Fig. 1D), and overweight or obese subjects (P < 0.001; Fig. 1F) compared to their controls. There was no significant difference in serum Maresin-1 levels among subjects with different LDL-C levels (P = 0.2587; Fig. 1E). Importantly, serum Maresin-1 levels in NAFLD patients were significantly decreased compared with those in non-NAFLD subjects (P = 0.000, Table 1).
Clinical and biochemical characteristics by quartiles of serum Maresin-1 in all study participants
Table 2 shows the clinical and biochemical characteristics according to quartiles of serum Maresin-1 levels in all subjects. BMI, WC, HC, WHR, SBP, DBP, FBG, ALT, AST, AST/ALT, GLO, A/G, GGT, ALP, Urea, TG, HDL-C, and Maresin-1 concentrations were significantly different between participants in different serum Maresin-1 quartiles (P < 0.05 or P < 0.01 or P < 0.001). Compared to subjects in the lowest quartile of serum Maresin-1 concentration, participants in the highest quartile had lower levels of BMI, WC, HC, WHR, SBP, DBP, FBG, WBC count, ALT, GLO, GGT, Urea, TC, TG, and LDL-C (P < 0.05 or P < 0.01 or P < 0.001) and higher levels of serum Maresin-1, AST/ALT, A/G, and HDL-C (P < 0.01 or P < 0.001). As shown in Fig. 2, the prevalence of NAFLD was rapidly decreased in tandem with increasing quartile of serum Maresin-1 levels (P < 0.001).
Table 2
Clinical and biochemical characteristics by quartile of serum Maresin-1 level in all subjects.
Variables | Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | P-value |
| ( ~ < 62.13) | (62.13 ≤ - < 68.71) | (68.71 ≤ - < 77.79) | ( ~ ≥ 77.79) | |
Sample Size | 60 | 60 | 60 | 60 | - |
Male/Female | 37/23 | 38/22 | 28/32 | 31/29 | 0.198 |
Age (year) | 46.00 (40.25–52.75) | 46.00 (34.00–54.00) | 38.50 (31.00-51.75) | 40.00 (31.25–49.75) | 0.075 |
BMI (kg/m2) | 26.13 (24.19–28.93) | 26.27 (23.75–28.25) | 25.23 (21.99–27.89) | 23.06 (21.17–25.60) *** | 0.000 |
WC (cm) | 89.20 ± 9.73 | 87.13 ± 9.39 | 83.67 ± 9.29 ** | 80.85 ± 8.83 *** | 0.000 |
HC (cm) | 99.00 (94.25–104.00) | 98.00 (93.00-102.00) | 97.50 (93.25–103.00) | 95.00 (92.00–99.00) * | 0.017 |
WHR | 0.90 (0.88–0.93) | 0.89 (0.84–0.92) | 0.85 (0.81–0.90) ** | 0.85 (0.80–0.88) *** | 0.000 |
SBP (mmHg) | 130.50 (118.00-137.00) | 123.00 (115.00-134.75) | 121.50 (111.00-134.75) | 120.00 (112.00-129.50) * | 0.038 |
DBP (mmHg) | 76.93 ± 10.84 | 75.95 ± 10.51 | 73.78 ± 10.31 | 71.20 ± 9.15 ** | 0.012 |
FBG (mmol/L) | 5.47 (4.86–5.81) | 5.09 (4.83–5.68) | 5.06 (4.73–5.38) * | 4.98 (4.68–5.27) ** | 0.001 |
WBC (*10^9/L) | 6.72 ± 1.45 | 6.59 ± 1.33 | 6.30 ± 1.17 | 6.17 ± 1.29 * | 0.079 |
NEU (*10^9/L) | 3.67 (3.08–4.47) | 3.69 (3.07–4.58) | 3.55 (3.11–4.12) | 3.67 (2.99–4.43) | 0.830 |
ALT (U/L) | 26.70 (19.45–38.18) | 27.40 (19.48–36.70) | 20.90 (13.33–30.35) * | 19.20 (13.98–27.88) ** | 0.000 |
AST (U/L) | 23.20 (19.45–29.63) | 23.30 (19.98–28.40) | 20.15 (16.83–26.38) | 20.15 (17.53–24.78) | 0.010 |
AST/ALT | 0.85(0.67–1.06) | 0.88(0.67–1.14) | 1.02(0.83–1.21) * | 1.11(0.85–1.28) ** | 0.000 |
TP (g/L) | 73.10 ± 2.88 | 73.01 ± 2.54 | 72.20 ± 3.37 | 72.95 ± 3.00 | 0.321 |
ALB (g/L) | 45.95 (45.00–47.00) | 45.85 (45.10-47.78) | 45.90 (44.90-47.48) | 47.25 (45.33–48.83) | 0.058 |
GLO (g/L) | 27.11 ± 3.05 | 26.64 ± 2.34 | 26.01 ± 2.44 * | 25.97 ± 2.20 * | 0.039 |
A/G | 1.72 (1.55–1.83) | 1.73 (1.60–1.88) | 1.79 (1.66–1.91) | 1.81 (1.73–1.94) * | 0.009 |
GGT (U/L) | 30.90 (19.23–47.33) | 29.10 (18.03–42.53) | 20.35 (14.68–31.40) * | 15.40 (12.68–28.30) *** | 0.000 |
ALP (U/L) | 73.85 (56.45–84.73) | 73.80 (62.43–84.70) | 72.15 (61.23–87.53) | 63.20 (52.40-79.13) | 0.031 |
Urea (mol/L) | 5.16 (4.83–5.96) | 4.98 (4.40–5.90) | 4.84 (3.97–5.77) | 4.76 (3.96–5.41) * | 0.027 |
UA (µmol/L) | 356.55 (296.10-418.60) | 362.35 (314.58-434.23) | 332.80 (283.48-400.93) | 318.55 (269.15-415.45) | 0.160 |
Crea (µmol/L) | 68.70 (55.95–75.25) | 66.70 (54.38–74.38) | 65.40 (52.63–73.78) | 65.20 (54.93–74.95) | 0.735 |
TC (mmol/L) | 5.00 ± 0.80 | 4.92 ± 0.75 | 4.74 ± 0.77 | 4.71 ± 0.67 * | 0.098 |
TG (mmol/L) | 1.81 (1.28–2.65) | 1.79 (1.23–2.63) | 1.37 (0.91–1.82) ** | 1.21 (0.90–1.69) *** | 0.000 |
HDL-C (mmol/L) | 1.10 (0.99–1.34) | 1.11 (0.96–1.24) | 1.24 (1.08–1.46) | 1.33 (1.17–1.63) ** | 0.000 |
LDL-C (mmol/L) | 3.42 ± 0.79 | 3.32 ± 0.82 | 3.24 ± 0.77 | 3.07 ± 0.72 * | 0.093 |
HCY (µmol/L) | 10.05 (8.40-11.78) | 10.10 (8.60–12.20) | 10.10 (8.70–11.90) | 10.15 (7.63–12.10) | 0.866 |
Continuous variables are mean ± standard deviation or medians (25th, 75th percentiles). *P < 0.05, **P < 0.01, ***P < 0.001 versus quartile 1 group. |
Association of Serum Maresin-1 Levels with Clinical Parameters in the Study Population
Next, correlation analysis was performed to investigate the association of serum Maresin-1 levels and other clinical parameters. As shown in Table 3, in all study population, serum Maresin-1 concentrations were positively associated with AST/ALT, ALB, A/G, and HDL-C (P < 0.05 or P < 0.01 or P < 0.001) and were negatively associated with Age, BMI, SBP, WC, HC, WHR, WBC count, ALT, AST, GLO, GGT, Urea, TG, LDL-C, and FBG (P < 0.05 or P < 0.01 or P < 0.001). After adjusting for sex and age, Maresin-1 remained statistically positively associated with AST/ALT, ALB, A/G, and HDL-C (P < 0.05 or P < 0.01 or P < 0.001) and negatively associated with BMI, WC, HC, WHR, ALT, GGT, UA, TG, and FBG (P < 0.05 or P < 0.01 or P < 0.001).
Table 3
The correlations analysis of variables associated with serum Maresin-1 levels in study population.
| Serum Maresin-1 | Serum Maresin-1 (age- and sex-adjusted) |
| r | P-value | r | P-value |
Sex | 0.114 | 0.078 | - | - |
Age | -0.171 | 0.008 | - | - |
BMI | -0.331 | 0.000 | -0.318 | 0.000 |
WC | -0.329 | 0.000 | -0.294 | 0.000 |
HC | -0.204 | 0.001 | -0.224 | 0.000 |
WHR | -0.360 | 0.000 | -0.281 | 0.000 |
SBP | -0.211 | 0.001 | -0.093 | 0.152 |
DBP | -0.113 | 0.081 | -0.079 | 0.222 |
FBG | -0.285 | 0.000 | -0.186 | 0.004 |
WBC | -0.155 | 0.016 | -0.093 | 0.151 |
NEU | -0.060 | 0.352 | -0.015 | 0.823 |
ALT | -0.289 | 0.000 | -0.212 | 0.001 |
AST | -0.214 | 0.001 | -0.102 | 0.116 |
AST/ALT | 0.260 | 0.000 | 0.240 | 0.000 |
TP | 0.016 | 0.810 | 0.006 | 0.931 |
ALB | 0.157 | 0.015 | 0.172 | 0.008 |
GLO | -0.150 | 0.020 | -0.123 | 0.058 |
A/G | 0.204 | 0.002 | 0.156 | 0.016 |
GGT | -0.358 | 0.000 | -0.158 | 0.015 |
ALP | -0.119 | 0.065 | -0.085 | 0.193 |
Urea | -0.211 | 0.001 | -0.125 | 0.055 |
UA | -0.126 | 0.051 | -0.129 | 0.048 |
Crea | -0.068 | 0.294 | -0.038 | 0.559 |
TC | -0.089 | 0.169 | -0.072 | 0.270 |
TG | -0.330 | 0.000 | -0.192 | 0.003 |
HDL-C | 0.255 | 0.000 | 0.242 | 0.000 |
LDL-C | -0.150 | 0.020 | -0.121 | 0.062 |
HCY | 0.002 | 0.977 | -0.013 | 0.837 |
Further, binary logistic regression analysis was performed to investigate the association of Maresin-1 with NAFLD. When no adjustment was made, serum Maresin-1 levels were significantly and inversely associated with the prevalence of NAFLD [OR = 0.945; 95% CI = 0.922–0.968, P = 0.000]. After adjusting for sex, age, BMI, SBP, DBP, WHR, and FBG or further adjusting for ALT, AST, AST/ALT and UA, the association between serum Maresin-1 levels and the presence of NAFLD was not affected [OR = 0.958, 95% CI = 0.928–0.989, P = 0.008] or [OR = 0.957, 95% CI = 0.926–0.989, P = 0.008]. Finally, even after adjusting for lipid profiles (TC, TG, HDL-C, and LDL-C), the Maresin-1 levels were significantly associated with NAFLD [OR = 0.965, 95% CI = 0.933–0.999, P = 0.042].