Pro-Inflammatory wnt5a and Anti-Inflammatory sFRP5 Are Differentially Regulated by Nutritional Factors in Obese Human Subjects

Background: Obesity is associated with macrophage infiltration of adipose tissue. These inflammatory cells affect adipocytes not only by classical cytokines but also by the secreted glycopeptide wnt5a. Healthy adipocytes are able to release the wnt5a inhibitor sFRP5. This protective effect, however, was found to be diminished in obesity. The aim of the present study was to examine (1) whether obese human subjects exhibit increased serum concentrations of wnt5a and (2) whether wnt5a and/or sFRP5 serum concentrations in obese subjects can be influenced by caloric restriction. Methodology: 23 obese human subjects (BMI 44.161.1 kg/m 2) and 12 age- and sex-matched lean controls (BMI 22.360.4 kg/m 2) were included in the study. Obese subjects were treated with a very low-calorie diet (approximately 800 kcal/d) for 12 weeks. Body composition was assessed by impedance analysis, insulin sensitivity was estimated by HOMA-IR and the leptin-to-adiponectin ratio and wnt5a and sFRP5 serum concentrations were measured by ELISA. sFRP5 expression in human adipose tissue biopsies was further determined on protein level by immunohistology. Principal Findings: Pro-inflammatory wnt5a was not measurable in any serum sample of lean control subjects. In patients with obesity, however, wnt5a became significantly detectable consistent with low grade inflammation in such subjects. Caloric restriction resulted in a weight loss from 131.964.0 to 112.363.2 kg in the obese patients group. This was accompanied by a significant decrease of HOMA-IR and leptin-to-adiponectin ratio, indicating improved insulin sensitivity

Anthropometric measurements before, during (1 month) and after 3 months of caloric restriction: Body composition was estimated by impedance analysis.

<p>Shown are means±SEM of n = 23 obese human subjects during a VLCD. Statistical significance was tested by student's t-test, ns = not significant.</p

Adipokine, wnt5a and sFRP5 serum concentrations before, during (1 month) and after 3 months of caloric restriction.

<p>Adipokine, wnt5a and sFRP5 serum concentrations before, during (1 month) and after 3 months of caloric restriction.</p

wnt5a and sFRP5 serum concentrations in lean control subjects and patients with obesity.

<p>Serum samples were taken after an overnight fast and wnt5a and sFRP5 serum concentrations were measured by ELISA. Shown are means±SEM for n = 12 lean control subjects and n = 23 patients with obesity. In order to test for statistical significance, student's t-test was used, ns = not significant.</p

(A+B) Insulin resistance before, during (1 month) and after 3 month of caloric restriction: In the present study insulin resistance was measured by the HOMA-IR index (A) and the leptin-to-adiponectin ration (LAR) (B) since the later parameter has been shown to be closely correlated to measures of insulin resistance by hyperinsulinemic euglycemic clamp experiments [<b>16</b>].

<p>Data are given as means±SEM of n = 23 obese human subjects during a VLCD. Significance was tested by student's t-test. (<b>C</b>) <i>sFRP serum concentrations before, during (1 month) and after 3 months of caloric restriction</i>: sFRP5 serum concentrations were determined before (0 month), during (1 month) and after (3 months) of a VLCD. In this figure the levels are shown as fold increase compared to 0 month. The raw data are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032437#pone-0032437-t002" target="_blank">table 2</a>. Shown are means±SEM of n = 23 obese human subjects during a VLCD. t-test was used to test for statistical significance.</p