Evidence Against a Role for Eosinophils in Adipose Tissue Health
Eosinophils are white blood cells distinguished by a multi-lobed nucleus and cytoplasm filled with granules that stain pink with hematoxylin and eosin stain. Known for their role in combatting parasitic infections and modulating allergic responses, eosinophils also regulate a wide array of other processes such as wound healing, the estrus cycle, GI tract remodeling, mammary gland development, and T-cell polarization. Recent research has revealed that eosinophils are also present in adipose tissue (AT), and various animal models of eosinophil deficiency or overabundance suggest that these cells promote weight control, glucose tolerance, and insulin sensitivity. The fact that eosinophil populations in the AT decrease in obesity suggests that these cells may play a critical role in maintaining AT health and overall metabolic homeostasis. Most studies of the effects of eosinophils on AT health, however, have focused on animals bearing gene mutations leading to life-long alterations in eosinophil number, or they have used methods that alter eosinophil populations in the context of potential off-target inflammatory or immune reactions. This led Basic Sciences investigator Alyssa Hasty and her laboratory to question whether the apparent effects of eosinophils might actually be due to other systemic changes present in the models used for their study. To address this question, they exposed mice to a high fat diet in the presence or absence of treatment with interleukin-5 (IL5), a cytokine known to promote eosinophil migration to AT. They showed that consistent with prior results, the high fat diet led to obesity in the mice and a concomitant reduction in AT eosinophils. Treatment with IL5 restored AT eosinophil numbers to those found in nonobese mice while having minimal effects on eosinophil populations in other body tissues. The investigators then embarked on a large series of studies to see if AT eosinophil restoration had any impact on weight gain or metabolism in obese mice consuming the high fat diet. They found no effect on food consumption, amount of weight gained, body composition, glucose tolerance, triglyceride tolerance, response to insulin signaling, metabolic parameters, or response to a cold challenge. These essentially negative findings call into question the hypothesis that eosinophils, per se, play a significant role in AT homeostasis, and they indicate a need for further research before that hypothesis becomes more widely accepted. The work is published in the journal Molecular Metabolism [W. R. Bolus, et al. Mol. Metab., (2017) published online Dec 16, DOI: 10.1016/j.molmet.2017.12.004].