Comparative analysis of liver enzymes in obese vs. non-obese adults

Introduction

Could the global obesity epidemic be silently compromising liver health across populations? The prevalence of obesity has reached alarming levels worldwide, with recent estimates suggesting that over 650 million adults qualify as obese based on body mass index criteria [1] . This metabolic condition extends its influence far beyond simple weight accumulation, affecting virtually every organ system in the human body [2] . The liver, serving as the central metabolic hub, appears particularly vulnerable to the consequences of excessive adiposity [3] . Hepatic enzymes represent sensitive indicators of liver cell integrity and function. Alanine aminotransferase and aspartate aminotransferase are predominantly intracellular enzymes that become elevated in serum when hepatocytes experience damage or increased membrane permeability [4] . GGT participates in glutathione metabolism and demonstrates particular sensitivity to fatty infiltration of the liver parenchyma [5] . ALP, while less specific to hepatic tissue, provides additional information regarding biliary function and cholestasis [6] . Together, these markers form the foundation of routine liver function assessment in clinical practice. Non-alcoholic fatty liver disease has emerged as the hepatic manifestation of metabolic syndrome, affecting an estimated 25% of the global population [7] . The pathophysiology involves triglyceride accumulation within hepatocytes, triggering inflammatory cascades and oxidative stress responses [8] . Obese individuals carry substantially higher risk for developing fatty liver, with prevalence rates approaching 80% in morbidly obese populations [9] . But the relationship between adiposity and liver enzyme abnormalities extends beyond simple fat deposition, involving complex hormonal and inflammatory mediators [10] . Previous investigations have documented associations between elevated BMI and abnormal liver biochemistry, yet several questions remain inadequately addressed [11] . The magnitude of enzyme elevation across different obesity categories requires further characterization. Additionally, the independent contribution of adiposity to hepatic dysfunction, separate from confounding factors like alcohol consumption and medication use, deserves careful examination [12] . Understanding these relationships carries important implications for clinical risk stratification and preventive care strategies. The French adult population presents an interesting context for examining obesity-related liver changes. While France historically maintained lower obesity rates compared to other Western nations, recent decades have witnessed concerning increases in overweight and obese individuals [13] . Regional variations exist, with certain areas showing higher metabolic disease burden [14] . Lyon and its surrounding communities represent a diverse urban population suitable for investigating these health relationships. This research aimed to compare serum liver enzyme concentrations between obese and non-obese adults while accounting for relevant confounding variables. We hypothesized that obese participants would demonstrate significantly elevated hepatic enzyme levels compared to their non-obese counterparts. Secondary objectives included evaluating correlations between BMI and individual enzyme values, and identifying independent predictors of liver enzyme abnormalities. The findings may contribute to improved screening recommendations and risk assessment protocols for individuals with excess body weight. (BMI <30 kg/m²) according to World Health Organization classifications [16] . Venous blood samples of 10 mL were collected from the antecubital vein using aseptic technique. Samples were allowed to clot at room temperature for 30 minutes before centrifugation at 3000 rpm for 10 minutes. Serum aliquots were separated and analyzed within 4 hours of collection. ALT and AST activities were determined using pyridoxal phosphate-activated kinetic methods. GGT measurement employed gamma-glutamyl-carboxynitroanilide substrate methodology. ALP activity was assessed using p-nitrophenyl phosphate as substrate at pH 10.4. Statistical analyses were performed using SPSS version 27.0 (IBM Corporation, Armonk, NY, USA). Continuous variables were expressed as mean±standard deviation following assessment for normality using Shapiro-Wilk tests. Between-group comparisons utilized independent samples t-tests for normally distributed variables. Pearson correlation coefficients evaluated relationships between BMI and enzyme levels. Multiple linear regression models assessed independent predictors of liver enzyme concentrations, adjusting for age, sex, alcohol consumption patterns, and concomitant medication use. Statistical significance was defined as p<0.05 for all analyses.

Material and Methods

Material

Ethical Considerations

This research received ethical approval from the Regional Ethics Committee for Biomedical Research at Université Claude Bernard Lyon 1 (Protocol CERB-2021-087, approved July 15, 2021). Written informed consent was obtained from all participants before enrollment, with documents provided in French and explained verbally by trained research coordinators. Participants received comprehensive information regarding research objectives, procedures, potential risks, and their right to withdraw at any time without consequences to their medical care. Personal data protection followed European Union General Data Protection Regulation requirements, with all identifying information stored separately from research data using coded linkage systems. Blood samples were processed anonymously using unique identification numbers, and remaining biological material was destroyed following analysis completion. Participants didn't receive financial compensation but were provided with their individual liver enzyme results and appropriate medical referrals when abnormalities were detected. Baseline demographic and anthropometric characteristics revealed important group differences. The obese cohort was slightly older than non-obese participants, reaching statistical significance (p=0.038). Sex distribution remained comparable between groups, with roughly equal male-tofemale ratios. As expected by design, BMI differed substantially, with mean values of 34.8±4.2 kg/m² versus 24.3±2.9 kg/m² (p<0.001).

Results

Waist circumference measurements confirmed central adiposity patterns in the obese group. Weekly alcohol consumption showed no significant difference, supporting appropriate matching for this potential confounder. Liver enzyme analysis revealed consistent elevations across all markers in obese participants. ALT showed nearly double the concentration compared to controls, with large effect sizes (Cohen's d=1.68) indicating clinically meaningful differences. AST followed similar patterns, though the magnitude of difference was somewhat smaller. GGT demonstrated the most pronounced disparity, consistent with its known sensitivity to hepatic steatosis. ALP elevation reached statistical significance but with moderate effect size, suggesting less specific hepatocyte involvement. The flowchart illustrates the systematic approach to participant selection and group assignment. Beginning with 847 initial screenings, rigorous exclusion criteria reduced the eligible pool while maintaining balanced group sizes.

The final cohorts of 198 obese and 214 non-obese participants provided adequate statistical power for detecting meaningful between-group differences.

Comprehensive Interpretation

Correlation analysis revealed positive associations between BMI and liver enzyme concentrations in both groups, but with notably steeper slopes in obese participants. The obese cohort demonstrated stronger correlation coefficients, suggesting that incremental weight gain produces proportionally greater hepatic impact once obesity thresholds are exceeded. Multiple regression modeling confirmed BMI as an independent predictor of ALT elevation (β=0.412, p<0.001), GGT elevation (β=0.387, p<0.001), and AST elevation (β=0.298, p<0.01) after adjusting for age, sex, alcohol consumption, and medication use. These findings support a dose-response relationship between adiposity and hepatic dysfunction.

Discussion

This research demonstrates consistent and clinically significant elevations in liver enzyme concentrations among obese adults compared to non-obese individuals. The findings align with existing literature documenting hepatic consequences of excessive adiposity while providing quantitative estimates specific to a French adult population. The magnitude of differences observed, particularly for ALT and GGT, suggests substantial hepatocyte involvement even in the absence of clinically diagnosed liver disease. The pronounced GGT elevation warrants particular attention. This enzyme serves as a sensitive marker for hepatic fat accumulation and demonstrates strong associations with metabolic syndrome components. Our finding of 98% higher mean GGT in obese versus non-obese participants exceeds several previous reports, possibly reflecting higher average BMI values in our obese cohort or population-specific factors. The correlation patterns further support GGT's utility as an early indicator of obesity-related liver changes. ALT elevation in obesity primarily reflects hepatocyte membrane damage from lipid accumulation and associated inflammatory responses. The observed 76% increase corresponds with established understanding of non-alcoholic fatty liver disease progression. Multiple regression results confirming BMI as an independent predictor strengthen the direct relationship between adiposity and hepatic dysfunction, separate from confounding influences of alcohol or medication effects.

Comparison with international data reveals both similarities and distinctions. Asian population studies often report steeper correlations between BMI and liver enzymes, possibly due to metabolically active visceral fat accumulation patterns at lower BMI thresholds. European cohorts generally show associations consistent with our findings, supporting generalizability within similar demographic contexts. The French population context adds valuable data to the broader understanding of obesity-liver relationships across different cultural and dietary environments.

Limitations

Several limitations merit acknowledgment when interpreting these results.

Acknowledgement

Acknowledgements Funding SourcesThis research received support from institutional research funds allocated by the Institut Européen de Recherche Médicale. The funding body had no involvement in research design, data collection, analysis, interpretation, or manuscript preparation.

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