Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans

Abstract

Context: Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.

Methods: Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.

Results: Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.

Conclusion: Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state.

Clinical trial registration: www.clinicaltrials.gov (NCT00562393).

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Relationships between circulating fatty acid binding protein 4 and fasting insulin (A) and percent body fat by DXA (B), and between adiponectin and visceral adipose tissue (C) and fasting serum non-esterified fatty acid (D) in men (empty circles) and women (dark circles).

Depicted are the line of fit and the 95% confidence curves that were obtained from linear regression. Abbreviations: FABP4, fatty acid binding protein 4; AT, adipose tissue; NEFA, non-esterified fatty acid.

Figure 2. Serum concentrations of fibroblast growth factor 21 (A), adiponectin (B), lipocalin-2 (C), fatty acid binding protein 4 (D) and plasminogen activating inhibitor 1 (E) at baseline and in response to overfeeding in healthy humans.

*P <0.05, **P ≤0.001. FABP4 data were log10-transformed prior to statistical analysis.

Figure 3. Associations between the change in adiponectin and change in weight (A) and BMI (B) and between the change in fatty acid binding protein 4 and change in fasting non-esterified fatty acid (C) and between the change in fibroblast growth factor 21 and resting metabolic rate (D) with overfeeding in men (empty circles) and women (dark circles).

Change was calculated as day 28 minus baseline (∆). Depicted are the line of fit and the 95% confidence curves that were obtained from linear regression. Abbreviations: BMI, body mass index; FABP4, fatty acid binding protein 4; FGF21, fibroblast growth factor 21; RMR, resting metabolic rate.