GRO-BAT · Growth hormone: an endocrine factor that integrates thermogenic and circadian signals to regulate brown adipose tissue activity.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-10-01 → 2018-09-30
- EU contribution
- €212,195
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Growth hormone: an endocrine factor that integrates thermogenic and circadian signals to regulate brown adipose tissue activity.
The intertwined diseases of obesity and diabetes is one of the greatest threats to health worldwide. The potent fat-burning and glucose-consuming functions of brown adipose tissue (BAT) make it an appealing avenue to target both obesity and diabetes. In addition to the classic adrenergic activation of BAT in the cold, it has recently been shown that heat production in BAT is tightly controlled by the body’s circadian rhythm. This breakthrough has opened up new approaches to better understand how thermogenesis in fat tissue is regulated by intrinsic cues from the molecular clock and extrinsic cues from environmental temperature. However, little is known about how these cues coordinate inter-organ signals to regulate the metabolic activity of the tissue. We have identified an endocrine system that may integrate environmental and circadian signals to suppress BAT activity. This endocrine system is suppressed in mice during cold activation of BAT and is increased when the circadian clock turns thermogenesis off during sleep. siRNA-mediated knockdown in vitro increases uncoupled respiration in brown and beige adipocytes. Loss-of-function genetic models show a disruption to circadian temperature regulation and increased heat production during cold exposure. Identification of a novel endocrine system that dually coordinates the cold response and circadian rhythm of adipose thermogenesis could lead to new approaches to increase energy consumption in brown and beige fat.
Data: CORDIS, © European Union
Project objective
The twin pandemic of obesity and diabetes is one of the greatest health challenges we face today. While fat is at the center of the problem, it may also be part of the solution. It has recently been shown that humans have brown or brown-like fat, whose primary function is to burn, rather than store, energy. This energy-consuming capacity of brown and brown-like fat has the potential to be harnessed to treat obesity and diabetes. The host supervisor has recently discovered that brown adipose tissue (BAT) metabolism is not only controlled by classic thermogenic regulation, but also by the circadian rhythm of the body’s molecular clock. During my PhD training, I observed a doubling in the size of interscapular BAT in mice that lack growth hormone receptor (GHR). I found that BAT has some of the highest levels of Ghr out of all tissues in the body. Despite this, the role of GHR in BAT remains unknown. My preliminary data suggests that GHR is a critical mediator of both thermogenic and circadian regulation. We propose to use genetic gain- and loss-of-function studies accompanied by pharmacologic modulation of GHR to determine its role in BAT. Our in vitro and in vivo work will be complemented by human studies to measure the fuel uptake and thermogenic capacity of BAT. The outcome will be highly relevant to human disease given the enormous potential of BAT activation in the treatment of obesity and diabetes.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union