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Sympathetic Wiring of Adipose Tissue

Project description

Insight into adipose tissue

Obesity is reaching epidemic proportions and requires novel interventions. It is well established that the autonomic nervous system (ANS) plays a critical role in energetic metabolism. Emerging evidence indicates that the ANS innervates adipose tissue (AT) and mediates lipolysis and fat mass reduction. The scope of the EU-funded CLEARFAT project is to study AT architecture and delineate the mechanism of AT innervation during development. Understanding how these mechanisms could lead to metabolic disturbance later in life has important clinical implications as it may lead to fat loss interventions that circumvent central leptin resistance.

Objective

Obesity is a metabolic disorder with unmet medical intervention strategies, for which a therapy is urgently needed. The Domingos Lab recently discovered that sympathetic (SNS) neuro-adipose junctions mediate lipolysis and fat mass reduction (Zeng et al., 2015). Thus, direct and targeted activation of SNS inputs to adipose tissues (AT) could represent a new strategy for the induction of fat loss that would circumvent central leptin resistance as well as historical challenges associated with drug delivery across the blood-brain-barrier. While it is known that the autonomic nervous system (ANS) plays a critical role in energetic metabolism through both its sympathetic and parasympathetic (PNS) branches; the mechanisms that underlie the development of the autonomic innervation of AT remain completely unexplored. Both the parasympathetic and sympathetic systems develop before birth, and autonomic nerve fibers can be observed in various peripheral organs as early as mid-gestation (Black, 1978; Burris and Hebrok, 2007; Rinaman and Levitt, 1993) although as AT originates at late gestation it is unclear how this late stage targeting may occur and how disruption to this process may impact metabolic profiles later in life. Although it has recently gained acceptance as an important endocrine organ, the cellular architecture of AT also remains elusive, as well as how this may be altered past hyperplasia and hypertrophy in pathological states. This has been due to the amorphous and unclearly defined nature of the tissue that becomes deformed and disrupted by classical dissection. The advent of whole body tissue clearing techniques allows us for the first time to study the architecture of AT and its inputs obviating the need for dissection and sectioning.

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 212 933,76
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76