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In obese microenvironments, ATF4 acts as a metabolic stress sensor, transcriptionally upregulating protein disulfide isomerase a3 (PDIA3) to drive TNF-, IL-6 and chemokine (C-C motif) ligand 2 (CCL2) production, thereby intensifying adipose tissue inflammation (177)

This indicates that they have the ability to replace the initial requirement for serum trophic factors in neuronal cultures

However, in another study reporting administration of NR or the CD38 inhibitor GSK987A to mdx mice for 20 weeks 267 , treated mice with the CD38 inhibitor showed increased NAD + levels in muscle tissue, but no improvement was found in muscle function after treatment with either the inhibitor or with NR

However, these compounds are widely distributed in nature and often suffer from poor bioavailability, raising questions about the translational relevance of their observed effects in vitro