IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis.

Stephan Wueest,Helga Ellingsgaard,Marc Y Donath,Daniel Konrad,Mark P Lyngbaek,Kristian Karstoft,Eleonora Seelig,Katharina Timper

doi:10.3390/metabo11020079

Abstract

Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (−2.7 ± 8.2% in the placebo vs. −20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.

Highlights

While leptin-induced regulation of food intake and energy expenditure may be impaired in obesity because of emerging leptin resistance, the identification of the pathways that regulate circulating adiponectin and leptin levels is of importance for a better understanding of the derangements of the glucose metabolism and body weight management in people with obesity
To investigate whether IL-6 impacts the circulating serum adiponectin and leptin levels in humans, adiponectin and leptin were determined in the serum from people with obesity infused with the IL-6 receptor antibody tocilizumab (n = 13) or a placebo (n = 9)
homeostatic model assessment of insulin resistance (HOMA-IR) (Figure 2B), indicating that increased adiponectin levels positively affect insulin sensitivity, as expected. This exploratory analysis revealed that long-term IL-6 receptor blockade in combination with exercise training impacts on the serum adiponectin levels in people with obesity

Summary

Introduction

Human obesity is associated with decreased adiponectin and elevated leptin levels, the latter resulting from an increased release by the expanding fat mass [1]. While adiponectin plays an important role in glucose metabolism by positively affecting insulin sensitivity, leptin is a key hormone in the regulation of body weight, as it reduces food intake and increases energy expenditure [1]. While leptin-induced regulation of food intake and energy expenditure may be impaired in obesity because of emerging leptin resistance, the identification of the pathways that regulate circulating adiponectin and leptin levels is of importance for a better understanding of the derangements of the glucose metabolism and body weight management in people with obesity

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