Abstract
Obesity is associated with chronic inflammation and elevated levels of IL-6. The role of IL-6 in induction of acute-phase proteins and modulation of hematological responses has been demonstrated in models of inflammation and aging, but not in obesity. We hypothesized that IL-6 is necessary to regulate the acute-phase response and hematological changes associated with diet-induced obesity (DIO) in mice. Feeding a 60%kcal/fat diet for 13weeks to C57BL6 WT male mice induced a significant increase in IL-6 expression in visceral adipose tissue (VAT), but not liver, compared to mice fed chow diet. Significantly elevated IL-6 levels were present in the peritoneal lavage fluid, but not plasma, of DIO compared to lean mice.A comparable degree of obesity, hepatomegaly, hyperleptinemia, VAT inflammation and insulin resistance was observed in DIO WT and IL-6 KO mice compared to WT and KO mice fed chow diet. Significant leukocytosis was observed in DIO WT but not DIO KO mice compared to lean groups. A significant reduction in platelet counts, without alterations in platelet size, percentage of circulating reticulated platelets and number of bone marrow megakaryocytes, was present in DIO KO mice compared to each other group. Hepatic expression of thrombopoietin was comparable in each group, with DIO WT and KO mice having reduced VAT expression compared to lean mice. Lean KO mice had significantly elevated plasma levels of thrombopoietin compared to each other group, whereas liver-associated thrombopoietin levels were comparable in each group. Deficiency of IL-6 resulted in blunted hepatic induction of the acute-phase protein serum amyloid A-1, whereas expression of hepcidin-1 and -2, LPS-binding protein, ceruloplasmin, plasminogen activator inhibitor-1 and thrombospondin-1 was IL-6-independent. In conclusion, in the absence of overt metabolic alterations, IL-6 modulates leukocytosis, thrombopoiesis and induction of SAA-1, but not other acute-phase proteins in obese mice.
Highlights
Obesity is associated with a state of chronic inflammation, characterized by infiltration by macrophages and other leukocytes in adipose tissue and increased production of several inflammatory mediators, including the pleiotropic cytokine IL-6 [1]
Results obtained from the present study demonstrate that IL-6 mediates modulation of serum amyloid A-1 (SAA-1) expression and participates in regulation of leukocytosis and thrombopoiesis in obese mice, whereas development of visceral adipose tissue (VAT) inflammation and induction of several acute-phase proteins in this model is independent of IL-6
IL-6 was significantly elevated in the peritoneal lavage fluid of dietinduced obesity (DIO) compared to lean WT mice, whereas only a non-significant trend was observed in circulating IL-6 levels (Fig 1)
Summary
Obesity is associated with a state of chronic inflammation, characterized by infiltration by macrophages and other leukocytes in adipose tissue and increased production of several inflammatory mediators, including the pleiotropic cytokine IL-6 [1]. Experimental evidence indicates the involvement of IL-6 in modulating development of obesity and insulin resistance in mice. Development of age-related obesity has been demonstrated in IL-6 KO (KO) mice fed a standard chow diet, with significant differences in body weight reported to begin at either 6 months [2] or 17-20 weeks of age [3]. Increased insulin resistance and exacerbated hepatic damage develop in KO mice fed a HFD for 20 weeks [3]. Overall the available data indicate that IL-6 regulates adipogenesis and glucose metabolism, suggesting that increased production of IL-6 in obesity might represent an attempt at protecting the organism against the damage associated with excessive fat accumulation and the associated development of chronic inflammation and insulin resistance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
