CLEARFAT · Sympathetic Wiring of Adipose Tissue
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-06-01 → 2022-05-31
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Sympathetic Wiring of Adipose Tissue
Obesity is one of the greatest public health challenges of the 21st century. Whilst obesity itself results in mechanical and psychological problems, the major concern is its association with leptin resistance, type 2 diabetes, fatty liver and a range of other disorders generally known as metabolic syndrome – also including sleep apnoea, musculoskeletal disorders, several types of cancer and cardiovascular disorders including stroke . Metabolic homeostasis is a complex biological process that depends on the overall metabolic rate, balanced between energy expenditure and energy storage. The brain and peripheral tissues are anatomically and functionally connected by the ANS, comprising two antagonistic divisions, the SNS and PNS. The SNS is a multifunctional system which plays an important role in the regulation of several metabolic processes and cardiovascular control. Neuro-adipose junctions with the sympathetic nervous system (SNS) mediate lipolysis and fat mass reduction6. 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. While it is known that the autonomic nervous system (ANS) plays a critical role in peripheral lipid metabolism through both its sympathetic and parasympathetic (PNS) branches; however, the mechanisms that underlie the development of the autonomic innervation of AT remain completely unexplored. Even though the functionality of the AT is well described as an endocrine organ with a tight crosstalk within central and peripheral nervous system, the complete architecture of AT also remains elusive, as well as how this may be altered past hyperplasia and hypertrophy in pathological states. The SNS provides a complex homeostatic control to co-ordinate function and crosstalk between white (WAT) and brown adipose tissue (BAT) through dense fibre innervation. Through the actions of the neurotransmitter norepinephrine, SNS modulates important physiological functions of WAT such as lipolysis, adipocyte regeneration and secretion of adipokines. WAT is a biological energy reservoir and a highly active endocrine and metabolic structure in mammals, that in response to over-nutrition expands and in response to energy deficits releases free-fatty acids.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union