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Decreased serum adiponectin: an early event in pediatric nonalcoholic fatty liver disease
Miriam Vos Louthan1, Shirish Barve, Craig J McClain
1Division of Gastroenterology and the Department of Pediatrics, University of Louisville, University of Louisville Medical Center, Louisville, Ky 40202, USA. mlouthan@childrensmemorial.org
Insights
Pediatric nonalcoholic fatty liver disease (NAFLD) is linked to lower adiponectin levels, not higher pro-inflammatory cytokines. This suggests reduced adiponectin is key in childhood NAFLD development.
Area of Science:
- Pediatric Endocrinology
- Hepatology
- Metabolic Syndrome
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a growing concern in children.
- The role of cytokines and adiponectin in pediatric NAFLD pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the serum concentrations of specific cytokines and adiponectin in children with presumed NAFLD.
- To compare these levels with those in normal-weight and overweight children.
Main Methods:
- A cohort of 30 children was studied, including those with presumed NAFLD (elevated Alanine aminotransferase [ALT]), overweight children, and normal-weight controls.
- Serum levels of adiponectin, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10 were measured.
- Ex vivo lipopolysaccharide stimulation was used to assess cytokine responses.
Main Results:
- Children with presumed NAFLD exhibited significantly lower mean serum adiponectin levels compared to normal-weight and overweight children.
- Serum adiponectin negatively correlated with body mass index, insulin, glucose, and ALT levels.
- No significant differences were observed in serum TNF-α, IL-6, IL-8, or IL-10 levels among the groups, nor in ex vivo stimulated cytokine production.
Conclusions:
- Reduced serum adiponectin is a characteristic finding in children with elevated ALT, mirroring adult observations.
- Unlike in adults, children with presumed NAFLD do not show elevated pro-inflammatory cytokine levels.
- These findings suggest that decreased adiponectin may play a more direct role than increased pro-inflammatory cytokines in the development of pediatric NAFLD.
Objective:
To evaluate the relative concentrations of cytokines in pediatric nonalcoholic fatty liver disease (NAFLD).
Study Design:
Thirty children were evaluated at a fasting morning visit to a pediatric research unit.
Results:
Compared with normal-weight children (n = 12) and children who were overweight (n = 11), children who had presumed NAFLD (elevated Alanine aminotransferase [ALT] with negative work-up) (n = 7) had significantly lower mean serum adiponectin levels (P = .004). Adiponectin negatively correlated with body mass index (r = -0.60, P = .001), insulin (r = -0.74, P < .001), glucose (r = -0.52, P = .004), and ALT (r = -0.53, P = .003). There was no difference between normal-weight, obese, and presumed NAFLD subjects in mean serum tumor necrosis factor alpha and interleukin-6 and -8 concentrations nor in tumor necrosis factor alpha and interleukin-8 and -10 levels in an ex vivo lipopolysaccharide-stimulated system.
Conclusions:
Serum adiponectin is reduced in children with elevated ALT, similar to adults. However, children with presumed NAFLD do not have elevated pro-inflammatory cytokine levels. This suggests that depressed adiponectin plays a more proximal role than elevated levels of circulating pro-inflammatory cytokines in the development of NAFLD in children.
