Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back

Abstract

Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.

The Role of Diet in Children with Psoriasis: Emerging Evidence and Current Issues

“…This evidence may be explained by preclinical data demonstrating that obesity and overweight are associated with an increase in inflammatory cytokines (e.g., IL-6 and TNF-), which represent key mediators in psoriasis [ 4 , 5 , 13 ].…”

“…As far as MD is concerned, unsaturated fats may affect immune-metabolic pathways [ 60 ]. In fact, oleic acid, a monounsaturated fat found in olive oil, protects cell membranes from harmful oxidative effects, and many polyunsaturated fatty acids, such as omega-3 and omega-6, are involved in the synthesis of anti-inflammatory and pro-inflammatory compounds, respectively [ 13 ]. In particular, omega-3 fatty acids compete with arachidonic acid to bind to COX-2 (cyclooxygenase-2), contributing to an anti-inflammatory effect.…”

“…This evidence may be explained by preclinical data demonstrating that obesity and overweight are associated with an increase in inflammatory cytokines (e.g., IL-6 and TNF-), which represent key mediators in psoriasis [4,5,13]. Also in the pediatric population, obesity and overweight, whose prevalence is growing (from 4% in 1975 to 18% in 2016, for a total of 380 million children), are associated with psoriasis [11,54,55].…”

“…At the molecular level, leptin, a protein with a dual role as a hormone and as a cytokine, could have a key role in the relationship between obesity and psoriasis. In fact, leptin promotes the inflammatory response, highlighting that adipose tissue, besides the underlying low-grade inflammation, secretes immunomodulatory molecules, primarily impairing Th2 responses, while reinforcing Th1 inflammatory responses [ 13 ]. Elevated leptin levels are found in the majority of obese patients, suggesting a state of leptin resistance [ 14 , 15 ].…”

Obesity Is Associated With Immunometabolic Changes in Adi-Pose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies

“…The innate immune cells, such as macrophages, respond to environmental danger signals that are released by the necrotic adipocytes that trigger chronic low-grade systematic inflammation via metabolic reprogramming [9]. During inflammation, there is an interplay between macrophages, that act as antigen-presenting cells, and adaptive immunity cells such as T-cells, by shaping T-cell responses and dysregulating the immunometabolic homeostasis towards a proinflammatory environment [10].…”