Professional Documents
Culture Documents
Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold
and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in
mice and humans, the events that lead from the sensing of cold to the development of beige
fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit,
consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13 and alternatively activated
macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced
biogenesis of beige fat. Mechanistically, macrophages recruited to cold-stressed subcutaneous
white adipose tissue (scWAT) undergo alternative activation to induce tyrosine hydroxylase
expression and catecholamine production, factors required for browning of scWAT.
Conversely, administration of IL-4 to thermoneutral mice increases beige fat mass and
thermogenic capacity to ameliorate preestablished obesity. Together, our findings have
uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its
targeting to treat obesity.
and studied, only in the last decade has it become apparent that the immune system plays a
broad and more subtle role in local and systemic metabolism. It is now apparent that the
immune system monitors and responds to specic metabolic cues in both pathologic and nonpathologic settings through a set of processes dubbed immunometabolism. Expansion of
adipose tissue mass, activation of lipolysis, eating a high fat diet and even non-shivering
thermogenesis all lead to the recruitment and activation of immune cells in key metabolic
tissues. The responses are complex and not completely dened, and indeed, as is typical of
rapidly evolving research areas, there are some conicting reports, especially related to the
metabolic consequences of manipulation of immune function. However, what is clear is the
consensus that metabolic processes, especially obesity and obesity-related complications,
activate both the innate and adaptive arms of the immune system. Canonical immune
processes consist of discrete steps: surveillance, recognition, effector action and resolution.
Over the last decade evidence for each part of the immune response has been found at the
intersection of the immune system with metabolism. Although evidence for immune
surveillance and modulation of metabolism has been found in the liver, muscle, hypothalamus
and pancreas, immune cell function has been most intensively studied and best understood in
adipose tissue where studies continue to provide insights into the intersection of the metabolic
and immune systems. Here we review the modulation of immune cell populations in adipose
tissue and discuss regulatory processes implicated in controlling the interface between
metabolism and immunologic function.