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In turn, this inhibits respiratory chain activity and mitophagy and induces oxidative damage and apoptosis in pancreatic islet -cells, leading to enhanced insulin resistance ( In vivo experiments further confirmed that PAA significantly reduced blood urea nitrogen (BUN) and proteinuria levels in STZ-induced DKD mice, inhibited the expression of IL-1 and TNF- in renal tissues, significantly increased the levels of LC3 and ATG5 proteins, and downregulated the levels of marker proteins such as p62 and FUNDC1, suggesting that PAA can improve renal dysfunction in DKD mice by downregulating FUNDC1 activation of mitophagy (Wu et al., 2023)

After the initial baseline challenge, subjects were placed on a week-long oral regimen of a cocktail of poorly absorbed antibiotics previously shown to effectively suppress intestinal microbiota (6), and then the d 3 -l-carnitine challenge was repeated (Figure 1, open circles)

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