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Publication
Lack of adipocyte purinergic P2Y6 receptor greatly improves whole body glucose
homeostasis.
Authors Jain S, Pydi SP, Toti KS, Robaye B, Idzko M, Gavrilova O, Wess J, Jacobson KA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2020
Date Published 12/1/2020
Volume : Pages 117 : 30763 - 30774
PubMed Reference 33199639
Abstract Uridine diphosphate (UDP)-activated purinergic receptor P2Y6 (P2Y6R) plays a
crucial role in controlling energy balance through central mechanisms. However,
P2Y6R's roles in peripheral tissues regulating energy and glucose homeostasis
remain unexplored. Here, we report the surprising finding that
adipocyte-specific deletion of P2Y6R protects mice from diet-induced obesity,
improving glucose tolerance and insulin sensitivity with reduced systemic
inflammation. These changes were associated with reduced JNK signaling and
enhanced expression and activity of PPARa affecting downstream PGC1a levels
leading to beiging of white fat. In contrast, P2Y6R deletion in skeletal muscle
reduced glucose uptake, resulting in impaired glucose homeostasis.
Interestingly, whole body P2Y6R knockout mice showed metabolic improvements
similar to those observed with mice lacking P2Y6R only in adipocytes. Our
findings provide compelling evidence that P2Y6R antagonists may prove useful for
the treatment of obesity and type 2 diabetes.




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