Extended Data Fig. 6: Myriocin remodels obesity and sphingolipid metabolism in serine-associated peripheral neuropathy.
From: Insulin-regulated serine and lipid metabolism drive peripheral neuropathy
(a) Thermal latency quantification in C57BL/6J mice fed with either a control diet (n = 10) or serine/glycine-free how (-Ser/Gly, n = 10) for 12 months. (b) Representative images of intraepidermal nerve fiber (IENF) density and quantification of IENF in paw skin in mice fed with either a control (n = 2) or serine/glycine free diet (n = 3) for 12 months. PGP9.5 staining of IENF is shown by arrows. (c) Body weight time course in mice fed with a low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (d) Body weight gain 6 months after dietary intervention in mice fed with a low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (e) Adipose tissue size 6 months after dietary intervention in mice fed with a low fat diet + vehicle (LFD+Veh, n = 9), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (f) Plasma amino acid concentration 6 months after dietary intervention in mice fed a with low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (g) Stack plot of liver ceramides in mice fed with a low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (h) Stack plot of sciatic nerve ceramides in mice fed with a low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). (i) Stack plot of sciatic nerve deoxydihydroceramide (deoxyDHCer) in mice fed a with low fat diet + vehicle (LFD+Veh, n = 10), LFD + 0.3 mg/kg myriocin (LFD+Myr, n = 10), serine/glycine-free LFD + vehicle (-SG LFD+Veh, n = 10), -SG LFD + myriocin (-SG LFD+Myr, n = 9), high fat diet + vehicle (HFD+Veh, n = 10), HFD + myriocin (HFD+Myr, n = 10), serine/glycine-free HFD + vehicle (-SG HFD+Veh, n = 10), and -SG HFD + myriocin (-SG HFD+Myr, n = 9). Data are mean ± standard error of mean (SEM) and were analyzed using a two-way ANOVA with Fisher’s LSD post hoc test (a and c) and a one-way ANOVA with Fisher’s LSD post hoc test (d–i). Statistical analyses in g-i were performed using summed sphingolipid abundances.
