Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the immune response. In metabolic disorders such as obesity, immune cells interact with various classes of lipids, which are capable of controlling the plasticity of macrophages and T lymphocytes. The purpose of this review is to discuss lipids and their impact on innate and adaptive immune responses, focusing on two areas: (1) the impact of altering lipid metabolism on immune cell activation, differentiation and function and (2) the mechanism by which lipids such as cholesterol and fatty acids regulate immune cell plasticity.

ObjectiveObesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are associated with impaired adipose tissue (AT) function. In the last decade, eosinophils have been identified as regulators of proper AT function. Our study aimed to determine whether normalizing the number of AT eosinophils in obese mice, to those of lean healthy mice, would reduce obesity and/or improve metabolic fitness.MethodsC57BL/6J mice fed a high fat diet (HFD) were simultaneously given recombinant interleukin-5 (rIL5) for 8 weeks to increase AT eosinophils. Metabolic fitness was tested by evaluating weight gain, AT inflammation, glucose, lipid, and mixed-meal tolerance, AT insulin signaling, energy substrate utilization, energy expenditure, and white AT beiging capacity.ResultsEosinophils were increased ∼3-fold in AT of obese HFD-fed mice treated with rIL5, and thus were restored to levels observed in lean healthy mice. However, there were no significant differences in rIL5-treated mice among the above listed comprehensive set of metabolic assays, despite the increased AT eosinophils.ConclusionsWe have shown that restoring obese AT eosinophils to lean healthy levels is not sufficient to allow for improvement in any of a range of metabolic features otherwise impaired in obesity. Thus, the mechanisms that identified eosinophils as positive regulators of AT function, and therefore systemic health, are more complex than initially understood and will require further study to fully elucidate.

Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity.

SummaryCetaceans are the only mammals to have evolved hyperphalangy, an increase in the number of phalanges beyond the mammalian plesiomorphic condition of three phalanges per digit. In this study, cetaceans were used as a novel model to review previous studies of mammalian hyperphalangy and contribute new experimental evidence as to the molecular origins of this phenotype in embryos of the pantropical spotted dolphin (Stenella attenuata). Results show embryos of dolphins, mice, and pigs share similar spatiotemporal patterns of signaling proteins known to shape limbs of mammals (e.g., and delphinids, and was probably associated with a wave of signaling within the interdigital tissues.

Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess free fatty acids and regulation of the extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron-handling genes. Although studies have demonstrated that iron homeostasis is important for adipocyte health, little is known about how MFe ATMs may respond to and influence adipose tissue iron availability. Two methodologies were used to address this question: dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe ATMs accumulated excess iron, whereas the iron content of MFe ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe ATMs incorporated high levels of iron, and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe ATM incorporation into the MFe pool. The MFe ATM population maintained its low inflammatory profile and iron-cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.