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

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.

Interleukin 6 as an energy allocator in muscle tissue

“…The data on the effect of adipocyte-specific IL-6 in genetically obese (ob/ob) mice are not consistent, as studies both support 101 and undermine 103 the assertion that adipocyte IL-6 leads to insulin resistance. In humans, a recent report suggests that administration of tocilizumab in people with obesity reduces HOMA-IR 104 . In total, there is no definitive consensus on whether IL-6 from adipose tissue derived from individuals with obesity leads to insulin resistance and allocates energy to adipose tissue inflammation.…”

Food Consumption and Metabolic Risks in Young University Students

“…In obesity, the IL-6 concentration increases, which decreases the sensitivity to insulin and increases glucose absorption in peripheral tissues [ 4 , 5 , 6 ], causing metabolic and cardiovascular diseases [ 7 ] and diabetes mellitus 2 [ 8 , 9 ]. Furthermore, adiponectin has been reported to increase adipocyte differentiation and inhibit IL-6 gene expression, which favors insulin sensitivity, preventing metabolic complications [ 10 , 11 ].…”

Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

“…Our data also indicate that therapeutic approaches to inhibit B cells, by reducing the levels of ACPAs anti-bodies, might provide a potential tool to control metabolic alterations induced by RA. In this sense, our longitudinal study Previous studies have demonstrated that the adipocytokine profile might be modulated by TNF-a and IL-6R inhibitors, although controversial results have been found (Derdemezis et al, 2009;Gonzalez-Gay et al, 2008Hoffman et al, 2019;Wueest et al, 2021).…”

“…Previous studies have demonstrated that the adipocytokine profile might be modulated by TNF-α and IL-6R inhibitors, although controversial results have been found ( Derdemezis et al., 2009 ; Gonzalez-Gay et al., 2008 , 2010 ; Hoffman et al., 2019 ; Wueest et al., 2021 ).…”