Interestingly, oleic and palmitic acid led to an increase of GRP78 at the message level but not at the protein level, which was lower than the control. C/EBP homologous protein has been identified as a crucial link between a dysfunctional ER stress and apoptosis and is a highly expressed gene during ER stress . Corresponding to the increased ER stress caused by FFAs, CHOP protein levels were increased. In contrast, exendin-4 reduced CHOP expression both at the protein and mRNA levels regardless of the FFA type loaded . It is noteworthy that while all the fatty acids induced the expression of CHOP, exendin-4 treatment LY294002 customer reviews suppressed the levels three fold in both oleic and palmitic acid loaded hepatocytes in comparison to elaidic acid. We did not find significant difference in 18s rRNA expression levels between treatments . Recently, macroautophagy has been identified as a mechanism for removal of fatty acid loads from hepatocytes. We wanted to confirm if GLP-1 analogs induced autophagy in fat loaded cells. Examination of autophagy related genes and proteins revealed that GLP-1 analog treatments both in vitro and in vivo increased key proteins associated with macroautophagy. Beclin and LC3B-II are two key proteins associated with macroautophagy. Exendin-4 significantly increased beclin protein levels except in oleic acid-treated hepatocytes where the change was insignificant; and exendin-4 also significantly increased the conversion of LC3-B1 to LC3B-II . These observations were in agreement with mRNA expression levels also. Beclin expression levels were decreased in response to saturated fatty acid in contrast to unsaturated cis- or trans-fatty acids . Exendin-4 was unable to enhance these levels in cells treated with oleic acid. Providing exendin-4 after both elaidic and palmitic acids enhanced Beclin expression.
In an ideal position to establish an H-bond with H221 explaining the high gain in potency
Leave a reply