Deficiency of haematopoietic-cell-derived IL-10 does not exacerbate high-fat-diet-induced inflammation or insulin resistance in mice

Abstract

Aims/hypothesis Recent work has identified the important roles of M1 pro-inflammatory and M2 anti-inflammatory macrophages in the regulation of insulin sensitivity. Specifically, increased numbers of M2 macrophages and a decrease in M1 macrophages within the adipose tissue are associated with a state of enhanced insulin sensitivity. IL-10 is an anti-inflammatory cytokine and is a critical effector molecule of M2 macrophages. Methods In the present study, we examined the contribution of haematopoietic-cell-derived IL-10 to the development of obesity-induced inflammation and insulin resistance. We hypothesised that haematopoietic-cell-restricted deletion of IL-10 would exacerbate obesity-induced inflammation and insulin resistance. Lethally irradiated wild-type recipient mice receiving bone marrow from either wild-type or Il10-knockout mice were placed on either a chow or a high-fat diet for a period of 12 weeks and assessed for alterations in body composition, tissue inflammation and glucose and insulin tolerance. Results Contrary to our hypothesis, neither inflammation, as measured by the activation of pro-inflammatory stress kinases and gene expression of several pro-inflammatory cytokines in the adipose tissue and liver, nor diet-induced obesity and insulin resistance were exacerbated by the deletion of haematopoietic-cell-derived IL-10. Interestingly, however, Il10 mRNA expression and IL-10 protein production in liver and/or adipose tissue were markedly elevated in Il10-knockout bone-marrow-transplanted mice relative to wild-type bone marrow-transplanted mice. Conclusions/interpretation These data show that deletion of IL-10 from the haematopoietic system does not potentiate high-fat diet-induced inflammation or insulin resistance.

Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications

“…IL-10 may have a protective anti-inflammatory role in muscle tissue. However, bone-marrow transplantation from IL-10-null mice into irradiated mice did not worsen inflammation in adipose and liver tissues or insulin resistance of the latter upon high-fat feeding (64). Of note, however, this was confounded by augmented IL-10 expression in adipose and liver tissues but normal circulating IL-10.…”

Inflammation during obesity is not all bad: evidence from animal and human studies

“…Whether IL-10 alters food intake and/or energy expenditure has not been evaluated. Interestingly, hematopoietic inactivation of IL-10 did not alter the response of the mice to an HFD (66), suggesting that the low adiposity of IL-10 KO mice is not due to loss of IL-10 in blood cells or macrophages. IL-10 infusion improved insulin sensitivity in rodents (59).…”

Bone marrow transplantation as an established approach for understanding the role of macrophages in atherosclerosis and the metabolic syndrome

“…Interleukin 10 Il10 À/À or WT C57Bl/6 HFD Obesity-related inflammation was increased [53] No effects on insulin resistance…”