| First Author | Datta R | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 3 | Pages | 112249 |
| PubMed ID | 36924494 | Mgi Jnum | J:347603 |
| Mgi Id | MGI:7463829 | Doi | 10.1016/j.celrep.2023.112249 |
| Citation | Datta R, et al. (2023) MFGE8 links absorption of dietary fatty acids with catabolism of enterocyte lipid stores through HNF4gamma-dependent transcription of CES enzymes. Cell Rep 42(3):112249 |
| abstractText | Enterocytes modulate the extent of postprandial lipemia by storing dietary fats in cytoplasmic lipid droplets (cLDs). We have previously shown that the integrin ligand MFGE8 links absorption of dietary fats with activation of triglyceride (TG) hydrolases that catabolize cLDs for chylomicron production. Here, we identify CES1D as the key hydrolase downstream of the MFGE8-alphavbeta5 integrin pathway that regulates catabolism of diet-derived cLDs. Mfge8 knockout (KO) enterocytes have reduced CES1D transcript and protein levels and reduced protein levels of the transcription factor HNF4gamma. Both Ces1d and Hnf4gamma KO mice have decreased enterocyte TG hydrolase activity coupled with retention of TG in cLDs. Mechanistically, MFGE8-dependent fatty acid uptake through CD36 stabilizes HNF4gamma protein level; HNF4gamma then increases Ces1d transcription. Our work identifies a regulatory network that regulates the severity of postprandial lipemia by linking dietary fat absorption with protein stabilization of a transcription factor that increases expression of hydrolases responsible for catabolizing diet-derived cLDs. |
