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. Author manuscript; available in PMC: 2022 Jul 6.
Published in final edited form as: Cell Metab. 2021 Jul 6;33(7):1293–1306. doi: 10.1016/j.cmet.2021.06.006

Figure 3. Ceramide modulation and tissue-specific effects on cellular metabolism.

Figure 3.

Ceramides generated during the progression of metabolic disease activate protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ), which inhibit AKT activation and reduce insulin signaling and glucose uptake. (A) Hepatic ceramides also reduce mitochondrial function and increase lipid accumulation. (B) Adipose tissue ceramides are also linked to decreased fatty acid β-oxidation and lipolysis. (C) In muscle, excess ceramides inhibit expression of the myokine FGF21, a key regulator of glucose metabolism. White boxes highlight the sphingolipid biosynthetic enzymes shown to affect metabolic outcomes when altered in vivo.