IL-6: A Potential Role in Cardiac Metabolic Homeostasis

Abstract

Interleukin-6 (IL-6) is implicated in multiple biological functions including immunity, neural development, and haematopoiesis. Recently, mounting evidence indicates that IL-6 plays a key role in metabolism, especially lipid metabolic homeostasis. A working heart requires a high and constant energy input which is largely generated by fatty acid (FA) β-oxidation. Under pathological conditions, the precise balance between cardiac FA uptake and metabolism is perturbed so that excessive FA is accumulated, thereby predisposing to myocardial dysfunction (cardiac lipotoxicity). In this review, we summarize the current evidence that suggests the involvement of IL-6 in lipid metabolism. Cardiac metabolic features and consequences of myocardial lipotoxicity are also briefly analyzed. Finally, the roles of IL-6 in cardiac FA uptake (i.e., serum lipid profile and myocardial FA transporters) and FA metabolism (namely, β-oxidation, mitochondrial function, biogenesis, and FA de novo synthesis) are discussed. Overall, understanding how IL-6 transmits signals to affect lipid metabolism in the heart might allow for development of better clinical therapies for obesity-associated cardiac lipotoxicity.

Secreted Protein Acidic and Rich in Cysteine: Metabolic and Homeostatic Properties beyond the Extracellular Matrix Structure

“…This would result in a cellular profile adapted to the changes that tissues undergo in terms of energy usage and storage and homeostatic needs. Moreover, the implications of the ECM [46] or SPARC [49][50][51][52] in other nonstructural functions such as inflammation, immunity, and cell growth would not only emphasize the importance of uncovering more pathways that ECM and SPARC govern but would also strengthen knowledge of metabolics, especially of links that have been established between cytokine (involved in inflammation and immunity) and metabolism [53][54][55]. Herein, cancer would be an illustrative example of such a "cell development-metabolism synchronization".…”

Pathological Responses of Cardiac Mitochondria to Burn Trauma

“…Notably, high IL-6 levels are sustained in burn animals (at 14 days post-burn) and associated with significantly increased heart mass [ 118 ], implying that chronic cardiac alterations may occur in burn patients due to sustained high IL-6 levels. On the other hand, accumulated evidence has suggested a key role of IL-6 in metabolic regulation [ 119 ]. IL-6 has been reported to regulate peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, thus impacting mitochondria biogenesis [ 119 ].…”

“…On the other hand, accumulated evidence has suggested a key role of IL-6 in metabolic regulation [ 119 ]. IL-6 has been reported to regulate peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, thus impacting mitochondria biogenesis [ 119 ]. Lower cardiac PGC-1α levels were observed in IL-6 knockout mice than in wild type mice fed a high-fat diet [ 120 ], and ablation of IL-6 impaired mitochondria synthesis [ 121 ].…”

Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome before and after long-term continuous positive airway pressure treatment

“…Interleukin-6 (IL-6) is a pleiotropic cytokine with both pro-and anti-in ammatory capacities, produced by different cells and tissues, such as leukocytes, adipocytes, and endothelium [1,2]. Accordingly, elevated concentrations of IL-6 may indicate an ongoing in ammatory response due to systemic or localized infection or chronic in ammatory disease [1][2][3][4]. IL-6 plasma levels correlate with NF-κB-dependent endothelial dysfunction, arterial stiffness, and the extent of subclinical atherosclerosis [1,2].…”

“…Accordingly, elevated concentrations of IL-6 may indicate an ongoing in ammatory response due to systemic or localized infection or chronic in ammatory disease [1][2][3][4]. IL-6 plasma levels correlate with NF-κB-dependent endothelial dysfunction, arterial stiffness, and the extent of subclinical atherosclerosis [1,2]. IL-6 has also been implicated in metabolic regulation and especially in lipid metabolic homeostasis, being predictive of incident type 2 diabetes and obesity [3,4].…”