Regulation
Insulin, cholesterol derivatives, T3 and other endogenous molecules have been demonstrated to regulate the SREBP1c expression, particularly in rodents. Serial deletion and mutation assays reveal that both SREBP (SRE) and LXR (LXRE) response elements are involved in SREBP1c transcription regulation mediated by insulin and cholesterol derivatives. Peroxisome proliferation-activated receptor alpha (PPARĪ±) agonists enhance the activity of the SREBP1c promoter via a DR1 element at -453 in the human promoter. PPARĪ± agonists act in cooperation with LXR or insulin to induce lipogenesis.
A medium rich in branched-chain amino acids stimulates expression of the SREBP1c gene via the mTORC1/S6K1 pathway. The phosphorylation of S6K1 was increased in the liver of obese db/db mice. Furthermore, depletion of hepatic S6K1 in db/db mice with the use of an adenovirus vector encoding S6K1 shRNA resulted in down-regulation of SREBP1c gene expression in the liver as well as a reduced hepatic triglyceride content and serum triglyceride concentration.
mTORC1 activation is not sufficient to stimulate hepatic SREBP1c in the absence of Akt signaling, revealing the existence of an additional downstream pathway also required for this induction which is proposed to involve mTORC1-independent Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2.
FGF21 has been shown to repress the transcription of sterol regulatory element binding protein 1c (SREBP1c). Overexpression of FGF21 ameliorated the up-regulation of SREBP1c and fatty acid synthase (FAS) in HepG2 cells elicited by FFAs treatment. Moreover, FGF21 could inhibit the transcriptional levels of the key genes involved in processing and nuclear translocation of SREBP1c, and decrease the protein amount of mature SREBP1c. Unexpectedly, overexpression of SREBP1c in HepG2 cells could also inhibit the endogenous FGF21 transcription by reducing FGF21 promoter activity.
SREBP1c has also been shown to upregulate in a tissue specific manner the expression of PGC1alpha expression in brown adipose tissue.
Nur77 is suggested to inhibit LXR and downstream SREBP1c expression modulating hepatic lipid metabolism.
Read more about this topic: Sterol Regulatory Element-binding Protein
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