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MTOR SREBF1 (1 - 5 of 5)
PMID: 20193134
High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR.
... of mTOR activity ... rapamycin resulted in ... of SREBP-1c protein ...   (details)

MTOR SREBF1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 20193134

High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR.
Source

BMB reports (February 2010)

Abstract

High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR. The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-alpha (C/EBP-alpha) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory-element-binding protein (SREBP) -1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.

PMID: 20817607
Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective.
SREBP-1c can be induced by mTORC1, ...   (details)

MTOR SREBF1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC1   (MLST8   AKT1S1   RPTOR   MTOR )

PMID: 20817607

Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective.
Source

Current opinion in pharmacology (December 2010)

Abstract

Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective. Transcription of enzymes involved in FA and TAG synthesis is coordinately induced in lipogenic tissues by feeding and insulin treatment. The three major transcription factors involved are USF, SREBP-1c, and LXRa. New insights into the insulin-signaling pathway (s) that control (s) lipogenic gene transcription via these factors have recently been revealed. Dephosphorylation/activation of DNA-PK by PP1 causes phosphorylation of USF that in turn recruits P/CAF to be acetylated for transcriptional activation. SREBP-1c can be induced by mTORC1, bifurcating lipogenesis from AKT-activated gluconeogenesis. LXRa may serve as a glucose sensor and, along with ChREBP, may activate lipogenic genes in the fed state. Dysregulation of FA and TAG metabolism often contributes to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Transcription factors and signaling molecules involved in transcriptional activation of FA and TAG synthesis represent attractive targets for the prevention and treatment of metabolic diseases.

PMID: 21723501
Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways.
... the role of mTORC1 in ... of SREBP1c in ...   (details)

MTOR SREBF1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21723501

Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways.
Source

Cell metabolism (7/6/2011)

Abstract

Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that this induction is dependent on the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1. Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de novo lipogenesis. These phenotypes result from attenuation of Akt signaling driven by mTORC1-dependent insulin resistance. Therefore, 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. We provide evidence that this mTORC1-independent pathway involves Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2.

... mTORC1 activation ... not sufficient to ... hepatic SREBP1c in ...   (details)

MTOR SREBF1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 21723501

Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways.
Source

Cell metabolism (7/6/2011)

Abstract

Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Through unknown mechanisms, insulin activates the sterol regulatory element-binding protein (SREBP1c) transcription factor to promote hepatic lipogenesis. We find that this induction is dependent on the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 (LTsc1KO), which results in insulin-independent activation of mTORC1. Surprisingly, the LTsc1KO mice are protected from age- and diet-induced hepatic steatosis and display hepatocyte-intrinsic defects in SREBP1c activation and de novo lipogenesis. These phenotypes result from attenuation of Akt signaling driven by mTORC1-dependent insulin resistance. Therefore, 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. We provide evidence that this mTORC1-independent pathway involves Akt-mediated suppression of Insig2a, a liver-specific transcript encoding the SREBP1c inhibitor INSIG2.

PMID: 22449814
Connecting mTORC1 signaling to SREBP-1 activation.
... that mTORC1 regulates SREBP-1 activation ...   (details)

MTOR SREBF1

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Cause:  mTORC1   (MLST8   RPTOR   MTOR )

PMID: 22449814

Connecting mTORC1 signaling to SREBP-1 activation.
Source

Current opinion in lipidology (June 2012)

Abstract

Connecting mTORC1 signaling to SREBP-1 activation. [PURPOSE OF REVIEW] The implication of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) in promoting protein synthesis has been well described. Over the past years, several studies revealed that mTORC1 also plays a crucial role in promoting lipid biosynthesis and that such connection could be linked to diseases including obesity, nonalcoholic fatty liver disease (NAFLD), and cancer. Here, we review the mechanisms by which mTORC1 regulates lipid synthesis by focusing on the key signaling events that trigger hepatic de-novo lipogenesis in response to nutrients and insulin. [RECENT FINDINGS] mTORC1 promotes lipid synthesis by activating the transcription factor sterol regulatory element binding protein 1 (SREBP-1). Recent studies indicate that mTORC1 regulates SREBP-1 activation at multiple levels. Although mTORC1 was originally shown to be necessary and sufficient to activate SREBP-1 in vitro, new studies indicate that hyperactivation of mTORC1 is insufficient to trigger SREBP-1 activation and lipid biogenesis in vivo. These findings reveal that the molecular connection between mTORC1 and SREBP-1 is more complex than originally envisioned. [SUMMARY] The discovery of a connection between mTORC1 and SREBP-1 opens a new chapter in our understanding of the molecular mechanisms regulating de-novo lipogenesis. A better comprehension of these mechanisms is key for the development of new tools to treat NAFLD and its complications.