Effect of High Fat Feeding on Inflammatory Cytokines in Obese and Healthy Children
Authors: Chiu Abraham S. , Ganesan Goutham , Horvath Peter , Bachman Georgia , Zaldivar Frank P. , Galassetti Pietro R. 
Published: November 2023

Background and Rationale

Adult and pediatric obesity are associated with chronic inflammation. In adults, this inflammation, considered a major pathogenetic link to future development of cardiovascular disease, is manifested partly by the systemic elevation of circulating leukocytes and pro‐inflammatory cytokines. These alterations are present chronically in obese adults, and acutely exacerbated by elevations in circulating lipids. Despite the recent alarming increase in the prevalence of pediatric obesity, the interaction of hyperlipidemia and systemic inflammation remains poorly defined in children. The purpose of the study was therefore to determine the leukocyte and cytokine profile of obese (Ob) vs. non‐obese (Non‐ob) children (10–17 y.o) in response to the ingestion of a high‐fat dairy mixture.

Methods

Seven Ob (BMI ≥95%, 13.7+2.6 y.o., 3F) and 8 Non‐ob (13.3+1.7 y.o., 3F) children without cardiovascular complications were enrolled. During two separate visits, participants ingested a heavy cream mixture (1.5g fat/kg body weight) or placebo drink (non‐caloric vitamin water) after a 10–12 hr overnight fast. Blood was drawn at fasting (30 min following IV catheter insertion), one hour, and two hours after the drinks were given. Blood was centrifuged, plasma isolated and frozen at −80° until batch analysis by ELISA for MCP‐1, IL1‐RA, IL‐6. Lipid panel and differential blood counts were also analyzed at the three time points. Data were analyzed via 2‐way RM AVOVA, with Dunnet's post‐hoc test when appropriate.

Results

The heavy cream mixture caused a doubling of triglyceride concentrations from fasting for both Ob and Non‐ob children (95±17 to 207±47 Ob, 66±14 to 128±16 mg/dl Non‐ob). In response to fat‐feeding, both group's total white blood cell counts increased significantly after 2 hrs (6900±400 to 7900±600/ul Ob, p<0.0001; 5400±600 to 6000±600/ul Non‐ob, p=0.01). Throughout the study, plasma IL‐6 concentrations were elevated in Ob compared to Non‐ob (p=0.001). Interestingly, IL‐6 concentrations significantly further increased 2 hr after fat ingestion in Ob (1.4±0.2 to 2.0 ±0.3 pg/mL, p=0.01) but not Non‐ob (0.7±0.1 to 0.7±0.1 pg/mL)(see figure). IL‐1RA concentrations were elevated in Ob vs Non‐ob (361+64 vs 71+33 pg/mL, fasting, p=0.01) but did not increase with fat feeding in either group. MCP‐1 concentrations at fasting were similar in both groups (57±3, Ob, 50±5 pg/mL, Non‐ob), and were similarly, slightly increased by fat feeding (p=0.056).

Conclusions

Ob children display a chronically elevated immune profile with more circulating leukocytes, IL‐6, and IL‐1RA concentrations as compared to controls. Acute fat ingestion caused an increase in white blood cell counts in both Ob and Non‐ob children. Ob children, however, displayed a greater sensitivity to the pro‐inflammatory stimulus associated with fat ingestion, experiencing an additional increase in IL‐6 concentrations that was not observed in Non‐ob children. Clear understanding of the differential immune response between Ob and Non‐ob children to everyday stimuli may elucidate the key factors that contribute to development of future obesity‐related cardiovascular complications.

Support or Funding Information

NIH NICHD P01HD048721 & UL1 TR000153