Diurnal rhythms of autophagy: Implications for cell biology and human disease

Potential role of autophagy in modulation of lipid metabolism

“…The robust suppressive effect of insulin on autophagy likely accounts for the nearly complete absence of autophagosomes in livers of mice refed after a 48-h fasting period (39). Likewise, insulin may regulate diurnal cycles in autophagy flux, which in rat liver peaks at the end of the fasting period (light phase) and is minimal after refeeding, although direct regulation of autophagy by circadian clock genes has been also proposed (44). During prolonged fasting (starvation), autophagy exhibits a tonic elevated level even before circulating insulin levels completely lose diurnal fluctuations.…”

“…These suggest that, under starvation conditions, possibly distinctly from "physiological fasting," other factors like amino acids and glucagon could contribute to the regulation of autophagic flux (Ref. 44 and references therein).…”

GABARAPL1 (GEC1): Original or copycat?

“…36). It has been shown that the autophagy-related genes Vps4b and Bnip3, like Gabarapl1, undergo rhythmic variations.…”

Measuring Autophagy in Vivo

“…Thus, it is not surprising that there are several reports that autophagy also varies markedly in accordance with diurnal cycle. In key studies it was shown that the abundance of autophagic vacuoles determined with EM changes according to time of day, not only in energy storage tissues such as liver but also in other organs including heart and kidney 19,20 (Figure 11 The literature linking autophagy to circadian rhythm has recently been reviewed and potential implications to disease discussed 21 . More recently, it has been shown that the circadian variation in autophagy in mouse is also accompanied by a rhythmic expression of autophagy linked genes including ULK-1, GABARAP1, and Bnip3 which are in turn regulated via C/EBPb 22 .…”