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10.1016/j.cmet.2022.11.013 15 BianY.LiW.KremerD

Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat

In contrast, a high-protein diet enhanced renal IGF-1 levels only in normal rats, suggesting that the additional effects of a high-protein intake on compensatory renal hypertrophy are partially mediated by GH signaling.77 In fact, the renal anabolic effects of the high-protein diet are attenuated by the inhibition of the GH receptor.78 Particularly, protein and energy wasting (PEW) is commonly observed in hemodialysis patients and likely associated with a lower protein and caloric intake.79 In this respect, circulating IGF-1 has been well-established as a marker for nutritional deficiency in hemodialysis patients for decades.80,81 Thus, patients undergoing hemodialysis with decreased muscle mass and a history of infections often show decreased serum IGF-1 levels, showing high sensitivity (77%) and moderate specificity (52%) as a marker of nutritional status.82 Compared to controls on a low-protein diet, rats fed a high-protein diet showed increased IGF-1 levels in the serum, liver and glomerulus, but not in the renal cortex, which resulted in higher total body and kidney weight but not liver

The takeaway is that both glutathione and NAC have unique roles

This is interesting in the context of our finding of increased lactate in both pgACC and dACC [9], as well as of a similar finding by Mueller at al.in their MRSI study [13]