IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis.
Stephan WueestEleonora SeeligKatharina TimperMark P P LyngbækKristian KarstoftMarc Y DonathHelga EllingsgaardDaniel KonradPublished in: Metabolites (2021)
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.
Keyphrases
- insulin resistance
- high fat diet
- adipose tissue
- metabolic syndrome
- high fat diet induced
- type diabetes
- skeletal muscle
- double blind
- polycystic ovary syndrome
- clinical trial
- endothelial cells
- rheumatoid arthritis
- weight loss
- placebo controlled
- glycemic control
- randomized controlled trial
- low dose
- cardiovascular disease
- study protocol
- phase iii
- pluripotent stem cells
- juvenile idiopathic arthritis
- rheumatoid arthritis patients
- cross sectional
- induced pluripotent stem cells
- high dose
- binding protein
- physical activity
- weight gain