An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling

Abstract

Beige adipocytes have been recently shown to regulate energy dissipation when activated, and help organisms defend against hypothermia and obesity. Prior reports indicate beige-like adipocytes exist in adult humans and may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we uncovered that the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) is induced in subcutaneous fat during the activation of these cells, and that acetylcholine-producing immune cells within this tissue regulate this signaling pathway via paracrine mechanisms. CHRNA2 functions selectively in uncoupling protein 1 (Ucp1)+ beige adipocytes, increasing thermogenesis through a cAMP and PKA pathway. Furthermore, this signaling via CHRNA2 is conserved and present in human subcutaneous adipocytes. Inactivation of Chrna2 in mice compromises the cold-induced thermogenic response selectively in subcutaneous fat and exacerbates high-fat diet-induced obesity and associated metabolic disorders, indicating that even partial loss of beige fat regulation in vivo leads to detrimental consequences. Our results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors (nAChRs) in energy metabolism. These findings may lead to identification of therapeutic targets to counteract human obesity.

Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3)

“…This realisation provides us with an opportunity to re-evaluate the current model of type 2 immunity in adiposity and beiging by defining previously unknown or under-appreciated immune cells and the mechanisms underpinning their contribution to AT homeostasis. A recent study found that AT immune cells secrete acetylcholine that elicits beiging, highlighting the importance of haematopoietic cells in AT homeostasis 55 . Interestingly though, acetylcholine-producing cells were predominantly B cells, T cells and macrophages, leaving the contribution of other lineages, such as eosinophils, unresolved.…”

“Multiple human adipocyte subtypes and mechanisms of their development”

“…"Brite/beige" adipocyte progenitors display high expression levels of cytokine genes, which could modulate the local concentrations of immune and stromal cells, which in turn could affect fate determination. Indeed, multiple reports exist of paracrine interactions with immune cells that enhance thermogenic activation [47][48][49]. In addition to cytokines, progenitors that give rise to "brite/beige" adipocytes display enhanced expression of PTGS2, the rate-limiting step in prostaglandin synthesis.…”

Carbon Nanotube Yarn Microelectrodes Promote High Temporal Measurements of Serotonin Using Fast Scan Cyclic Voltammetry

“…The detection of dopamine is crucial for understanding Parkinson's disease and drug abuse [1], while selective serotonin reuptake inhibitors (SSRIs) are used as treatments for depression [2]. Neurochemical measurements are also important in studying other disease states such as epilepsy [3,4] and obesity [5]. In order to study neurochemical dynamics in vivo, scientists have used several bioanalytical assays such as microdialysis [6], positron emission tomography (PET) imaging [7], enzymatic biosensors [8], and carbon electrodes [9].…”