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Lack of Adipocyte Purinergic P2Y6 Receptor Greatly Improves Whole Body Glucose Homeostasis
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
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 novel 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 PPARα affecting downstream PGC1α 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 KO 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.
- Subjects :
- medicine.medical_specialty
Glucose uptake
Type 2 diabetes
White adipose tissue
Diet, High-Fat
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Adipocyte
Internal medicine
Adipocytes
medicine
Animals
Homeostasis
Glucose homeostasis
Obesity
Muscle, Skeletal
Receptor
030304 developmental biology
Inflammation
Mice, Knockout
0303 health sciences
Multidisciplinary
Receptors, Purinergic P2
Purinergic receptor
JNK Mitogen-Activated Protein Kinases
Biological Sciences
medicine.disease
Mitochondria
3. Good health
Disease Models, Animal
Uridine diphosphate
Glucose
Endocrinology
Adipose Tissue
Diabetes Mellitus, Type 2
Gene Expression Regulation
chemistry
Knockout mouse
Energy Metabolism
Biomarkers
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Proc Natl Acad Sci U S A
- Accession number :
- edsair.doi.dedup.....3bf39a7fac040e4b7fc1236805b0bc63