Successful metabolic adaptations leading to the prevention of high fat diet-induced XXXX cardiac remodeling.

@entity1 @entity296 @entity6 @entity3916 @entity28 @entity19 @entity1283 @entity1184 @entity26 @entity1735 @entity13088 @entity3240 @entity34020 @entity413
BACKGROUND: @entity296 is a devastating complication of @entity28 and @entity6 ( @entity6 ). It arises even in @entity1 with normoglycemia (glycosylated hemoglobin, @entity3916  <=7  %). As @entity28 and @entity6 are approaching epidemic levels worldwide, the @entity296 associated with these diseases must be therapeutically addressed. We have recently analyzed the systemic effects of a 12-week high fat diet (HFD) on wild type @entity19 from the C57Bl/6 (B6) strain and the wild type super-healing Murphy Roths Large (MRL) @entity19 . The MRL HFD @entity19 gained significantly more weight than their control diet counterparts, but did not present any of the other usual systemic @entity6 phenotypes. METHODS: Cardiac pathology and adaptation to HFD-induced @entity28 in the MRL @entity19 compared to the HFD C57Bl/6 @entity19 were thoroughly analyzed with echocardiography, histology, qPCR, electron microscopy and immunoblots. RESULTS: The @entity28 HFD C57Bl/6 @entity19 develop @entity1283 , cardiomyocyte lipid droplets, and initiate an ineffective metabolic adaptation of an overall increase in electron transport chain complexes. In contrast, the @entity28 HFD MRL hearts do not display @entity1184 nor lipid droplets and their metabolism adapts quite robustly by decreasing pAMPK levels, decreasing proteins in the @entity1735 metabolism pathway and increasing proteins utilized in the b-oxidation pathway. The result of these metabolic shifts is the reduction of toxic lipid deposits and reactive @entity26 species in the hearts of the @entity28 HFD fed MRL hearts. CONCLUSIONS: We have identified changes in metabolic signaling in @entity28 HFD fed MRL @entity19 that confer resistance to @entity13088 . The changes include a reduction of cardiac pAMPK, @entity3240 and @entity34020 in the MRL HFD hearts. Overall the MRL hearts down regulate @entity413 metabolism and favor lipid metabolism. These adaptations are essential to pursue for the identification of novel therapeutic targets to combat @entity28 related @entity296 .
