Page 18 - CIBERDEM2016-ENG

PROGRAMME 3. Cellular and molecular
mechanisms involved in the development
and progression of type 2 diabetes and
identification of new therapeutic targets
Coordinator: Antonio Zorzano Olarte
DETERMInIng FACTORS OF RESISTAnCE TO InSULIn: MOLECULAR MECHAnISMS
InVOLVED
Prospective longitudinal monitoring of newborn babies with low weight for their gestational age (SGA) has shown that they experience fast and exaggerated postnatal recovery growth and develop early resistance to insulin and increase of visceral and hepatic fat which in turn conditions a greater risk for the future development of diabetes (Sebastiani et al., Pediatr Obes 2016).
It has been shown that Mitofusin 2 (Mfn2) mitochondrial protein is repressed in the skeletal muscle of old mice, that knockout mice in which Mfn2 has been eliminated in the muscle display intolerance to glucose, mitochondrial dysfunction and muscular atrophy. This indicates that Mfn2 is a target for the development of new therapies for diabetes (Sebastián et al., EMBO J 2016).
Overexpression of Sirt1 in the skeletal muscle of the mouse has been proven to activate its oxidative capacity, but does not provide any protection against obesity and resistance to insulin (Vila et al., Mol Ther. Methods Clin Dev 2016). It has been described that an increase in the expression of Alox5ap can protect against obesity, inflammation, lipid steatosis and resistance to insulin (Elias et al. Diabetes 2016).
InFLAMMATIOn AS A PATHOgEnIC PROCESS In DIABETES MELLITUS: THE ROLE
OF ADIPOSE TISSUE AnD InTERACTIOn WITH OTHER TISSUES OR ORgAnS
We have established new interrelations between lipid metabolism and inflammation. Lipin -2, a lipid metabolism protein which regulates the levels of phosphatidic acid and diacylglycerol, acts as a key regulator in macrophages in molecular assembly generating interleukin 1, known as inflammasome nLRP3. This provides a molecular explanation of Majeed syndrome and provides a connection between lipid metabolism and inflammation, with some interesting possibilities for therapeutic manipulation (Lordén et al., J Exp Med 2016).
We have shown that the hostile environment of chronic inflammation associated with obesity and type 2 diabetes alters the immunological functional properties of the stem cells residing in adipose tissue (Serena et al., Stem Cells. 2016).
1283