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Neelakantan H, Vance V, Wetzel MD, Wang HY, McHardy SF, Finnerty CC, Hommel JD, Watowich SJ. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high-fat diet-induced obesity in mice. Biochem Pharmacol. 2018 Jul;154:161-171. doi: 10.1016/j.bcp.2018.05.003. Epub 2018 May 5. PMID: 29738706; PMCID: PMC6015571

This genetic metabolic block severely impairs the body's ability to produce cellular energy and clear out neurotoxins, directly contributing to the hallmark symptoms of ME/CFS, including profound post-exertional malaise (PEM) and unrefreshing sleep

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[] Furthermore, BNIP3, a critical mitophagy receptor, is a known transcriptional target of FOXO3, which itself can stimulate PGC-1 expression