Autophagy participants in the dedifferentiation of mouse 3T3-L1 adipocytes triggered by hypofunction of insulin signaling

Potential key factors involved in regulating adipocyte dedifferentiation

“…The significant reduction of Cebpb messenger RNA (mRNA) and protein level is again supportive for the enhancement of de‐differentiation (Pan et al, 2021). Intriguingly, compared to the inhibiting insulin signal alone, 3T3‐L1 adipocytes that simultaneously inhibit the insulin signal and enhance autophagy, exhibit a weaker insulin signal (Pan et al, 2021). In sum, autophagy may play a key role in promoting adipocyte de‐differentiation by inhibiting insulin signaling (Figure 3).…”

“…Together, these results suggest that insulin does have an inverse role in regulating adipocyte de‐differentiation (Figure 3). AKT is a key signal molecule for insulin signaling, and the total AKT level does not change before and after de‐differentiation (Pan et al, 2021). But the pAKT level in de‐differentiation was lower than that in differentiation.…”

“…Intriguingly, the latest research shows that autophagy/mTORC1 is involved in insulin‐driven adipocyte de‐differentiation (Pan et al, 2021). By blocking insulin signaling during adipocyte de‐differentiation, autophagy levels were elevated in 3T3‐L1 adipocytes, and the protein level of the autophagy substrate P62 was significantly increased (Pan et al, 2021). mTORC1 has been shown to negatively affect autophagy (Inoki et al, 2003).…”

“…mTORC1 has been shown to negatively affect autophagy (Inoki et al, 2003). Further, when a mTORC1 inhibitor was used to reverse the effect in 3T3‐L1 adipocytes, both LC3 level and LC3II/LC3I ratio were significantly upregulated in the late stage of de‐differentiation, and the expression of C/EBPβ and PPARγ decreased significantly (Pan et al, 2021). On the other hand, when autophagy in 3T3‐L1 adipocytes was inhibited by bafilomycin‐A1, lower de‐differentiation was observed compared with enhanced autophagy treatment (Pan et al, 2021).…”

“…mTORC1 has been shown to negatively affect autophagy (Inoki et al, 2003). Further, when a with enhanced autophagy treatment (Pan et al, 2021). However, simultaneous inhibition of insulin signaling and enhancement of autophagy accelerate the loss of lipid droplets in cells compared to the inhibition of insulin signaling alone, suggesting enhanced dedifferentiation.…”