IL-6: A Potential Role in Cardiac Metabolic Homeostasis

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obesity 17 endocrinologydiseases

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hypertriglyceridemia 5134 administration. Furthermore, IL-6 neutralizing antibody Actemra (tocilizumab) induces body weight gain, hypertriglyceridemia , and hypercholesterinemia in humans [[28]]. Interestingly, carriers of IL-6 gene polymorphism G174C
hypertriglyceridemia 12419 Moreover, long-term administration of humanized anti-IL-6 antibody Actemra (tocilizumab) results in hypertriglyceridemia in human subjects and the severity appears to increase in a time-dependent manner [[28]]. Furthermore,
obesity 1654 to affect lipid metabolism in the heart might allow for development of better clinical therapies for obesity -associated cardiac lipotoxicity.1. IntroductionDue to the functional pleiotropy of cytokines, interleukin-6
obesity 2608 metabolism. Wallenius et al. reported that IL-6 deficiency in mice results in the development of mature-onset obesity which is partially reserved by intracerebroventricular IL-6 injection [[18]]. Furthermore, mice overexpressing
obesity 6445 rodents also implicate a role of IL-6 in metabolic regulation. IL-6-deficient mice exhibit mature-onset obesity , with disrupted carbohydrate and lipid metabolism, which are partially reserved by intracerebroventricular
obesity 6781 IL-6 reduces relative weight of mesenteric and retroperitoneal fat pads, thereby suggesting the anti- obesity role of IL-6 [[32]]. Mice over-expressing human IL-6 have less visceral fat when fed a normal diet and
obesity 6934 human IL-6 have less visceral fat when fed a normal diet and are free from high-fat-diet (HFD)-induced obesity [[33]]. Direct delivery of murine IL-6 via adenoviral vector into rat hypothalamus results in suppressed
obesity 7603 expressing IL-6 or IL-6 receptors [[35]]. Given the above results, IL-6 is suggested to play an anti- obesity role in rodent metabolic homeostasis (Table 2).However, evidence against the anti-obesity role of IL-6
obesity 7693 play an anti-obesity role in rodent metabolic homeostasis (Table 2).However, evidence against the anti- obesity role of IL-6 during HFD feeding has been reported. Our group showed a significantly more pronounced
obesity 8115 body weight gain during HFD feeding [[33]]. Furthermore, Gregorio et al. failed to detect late-onset obesity or disturbed lipid metabolism in IL-6−/− mice reported by Wallenius et al. [[37]]. Although it remains
obesity 8709 level observed in IL-6−/− mice were more severe than those in WT after HFD. Therefore, the anti- obesity effect of IL-6 deficiency during HFD could be a secondary symptom during HFD-induced obesity. Taken
obesity 8802 the anti-obesity effect of IL-6 deficiency during HFD could be a secondary symptom during HFD-induced obesity . Taken together, current evidence suggests that IL-6 is involved in metabolic regulation, especially
obesity 9686 maintained to ensure that no excess FA is accumulated in myocardium. However, metabolic disorders including obesity and diabetes tilt the balance towards enhanced uptake and/or reduced FA utilization [[40],[41]]. Although
obesity 14736 ceramide [[54]]. Our group also noticed that cardiac FAT/CD36 mRNA levels increase during HFD-induced obesity in both WT and IL-6−/− mice [[36]]. However, the elevation is significantly more pronounced in IL-6−/−
obesity 20032 thereby suggesting that IL-6 partially protects against suppressed expression of PGC-1α induced by obesity [[67]]. Decreased expression of PGC-1α in Drosophila results in reduced inhibition of FA synthase,
obesity 28975 cardiomyopathy. Decoding the activators and effectors of IL-6 in cardiac lipotoxicity during HFD-induced obesity will provide cues for treatment of obesity-associated dyslipidemia and cardiac lipotoxicity, and improve
obesity 29018 effectors of IL-6 in cardiac lipotoxicity during HFD-induced obesity will provide cues for treatment of obesity -associated dyslipidemia and cardiac lipotoxicity, and improve development of novel drug therapies.Figure
obesity 34434 control in rodents.Species/DescriptionTreatmentObserved EffectsReferenceMice/IL-6 KOn.d.Mature-onset obesity : Increased weight of subcutaneous fat pad[[18]]Mice/IL-6 KO; HFDIntracerebroventricular IL-6 injection
obesity 34842 intake; Increased energy expenditure; Reduced visceral fat on normal chow and free from HFD-induced obesity [[33]]Rat/maleDirect delivery of recombinant adeno-associated viral vector expressing murine IL-6 into

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