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. 2022 Apr 12;23(5):e52412. doi: 10.15252/embr.202152412

Figure 4. Ketogenic diet (KD)‐induced reprogramming of peripheral clocks and metabolic homeostasis.

Figure 4

KD remodels rhythms differently in the liver and intestine. KD enhances BMAL1 recruitment to target genes in the liver, thereby increasing the amplitude of CCGs oscillations. KD activates PPARα signaling both in the liver and intestine. However, robust oscillations can be observed only in the intestine. KD‐induced ketogenesis increases serum β‐OHB concentration and circadian oscillations. The local intestinal concentration of β‐OHB mirrored the profile of serum β‐OHB, leading to time‐dependent HDAC activity and histone acetylation. BMAL1, brain and muscle ARNT‐like 1; β‐OHB, β‐hydroxybutyrate; CCGs, clock‐controlled genes; CPT‐1α, carnitine palmitoyltransferase 1α; HDAC, histone deacetylases; HMGCS2, 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2; PPARα, peroxisome proliferator‐activated receptor alpha.