Nme7 Mutation Affects Glucose Tolerance in Rats
Nme7 is a Protein Coding gene. Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors.
The family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions.
But several lines of evidence from human and experimental studies point to the potential involvement of one of its members.
This member is NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism.
As a complete lack of Nme7 is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous +/− on male rats vs. their wild-type +/+ controls.
Nme7+/− animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance.
Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage.
Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of Nme7+/− male rats with a concerted increase of expression of lipogenic enzymes including Scd1, Fads1, Dhcr7 and a decrease of Cyp7b1.
Network analyses suggested possible links between these cells and the activation of Srebf1 and Srebf2 upstream regulators.
These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity.