PMID- 31475823
OWN - NLM
STAT- MEDLINE
DCOM- 20191010
LR  - 20211204
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 67
IP  - 37
DP  - 2019 Sep 18
TI  - CRTC2 Is a Key Mediator of Amino Acid-Induced Milk Fat Synthesis in Mammary 
      Epithelial Cells.
PG  - 10513-10520
LID - 10.1021/acs.jafc.9b04648 [doi]
AB  - Amino acids can stimulate milk fat synthesis, but the underlying molecular 
      mechanism is still largely unknown. In this study, we studied the regulatory role 
      and corresponding molecular mechanism of cAMP response element-binding 
      protein-regulated transcription coactivator 2 (CRTC2) in amino acid-induced milk 
      fat synthesis in mammary epithelial cells. We showed that leucine and methionine 
      stimulated CRTC2 but not p-CRTC2(Ser171) expression and nuclear localization in 
      cow mammary epithelial cells. Knockdown of CRTC2 decreased milk fat synthesis and 
      sterol regulatory element binding protein 1c (SREBP-1c) expression and 
      activation, whereas its overexpression had the opposite effects. Neither 
      knockdown nor overexpression of CRTC2 affected beta-casein synthesis and 
      phosphorylation of the machanistic target of rapamycin (mTOR), suggesting that 
      CRTC2 only regulates milk fat synthesis. CRTC2 knockdown abolished the 
      stimulation of leucine and methionine on SREBP-1c expression and activation. 
      Knockdown or overexpression of CRTC2 did not affect the protein level of 
      cAMP-response element-binding protein (CREB) and its phosphorylation but 
      decreased or increased the binding of p-CREB to the promoter of SREBP-1c gene and 
      its mRNA expression, respectively. Mutation of Ser171 of CRTC2 did not alter the 
      stimulation of CRTC2 on SREBP-1c expression and activation, further suggesting 
      that CRTC2 functions in the nucleus. mTOR inhibition by rapamycin totally blocked 
      the stimulation of leucine and methionine on CRTC2 expression. The expression of 
      CRTC2 was dramatically higher in the mouse mammary gland of lactation period, 
      compared with that of the dry and puberty periods, whereas p-CRTC2(Ser171) was 
      not changed, further supporting that CRTC2 is a key transcription coactivator for 
      milk fat synthesis. These results uncover that CRTC2 is a key transcription 
      coactivator of amino acid-stimulated mTOR-mediated milk fat synthesis in mammary 
      epithelial cells.
FAU - Li, Ping
AU  - Li P
AD  - School of Animal Science , Yangtze University , Jingzhou 434020 , China.
FAU - Zhou, Chengjian
AU  - Zhou C
AD  - The Key Laboratory of Dairy Science of Education Ministry , Northeast 
      Agricultural University , Harbin 150030 , China.
FAU - Li, Xueying
AU  - Li X
AD  - The Key Laboratory of Dairy Science of Education Ministry , Northeast 
      Agricultural University , Harbin 150030 , China.
FAU - Yu, Mengmeng
AU  - Yu M
AD  - The Key Laboratory of Dairy Science of Education Ministry , Northeast 
      Agricultural University , Harbin 150030 , China.
FAU - Li, Meng
AU  - Li M
AD  - The Key Laboratory of Dairy Science of Education Ministry , Northeast 
      Agricultural University , Harbin 150030 , China.
FAU - Gao, Xuejun
AU  - Gao X
AUID- ORCID: 0000-0002-8241-6346
AD  - School of Animal Science , Yangtze University , Jingzhou 434020 , China.
LA  - eng
PT  - Journal Article
DEP - 20190910
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Amino Acids)
RN  - 0 (Crtc2 protein, mouse)
RN  - 0 (Fats)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acids/*metabolism
MH  - Animals
MH  - Cattle/genetics/*metabolism
MH  - Epithelial Cells/*metabolism
MH  - Fats/*metabolism
MH  - Female
MH  - Mammary Glands, Animal/*cytology/metabolism
MH  - Mice
MH  - Milk/*metabolism
MH  - Phosphorylation
MH  - Sterol Regulatory Element Binding Protein 1/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
OTO - NOTNLM
OT  - SREBP-1c
OT  - cAMP-response element-binding protein
OT  - cAMP-response element-binding protein-regulated transcription coactivator 2
OT  - leucine
OT  - mTOR
OT  - mammary epithelial cells
OT  - methionine
OT  - milk fat synthesis
EDAT- 2019/09/03 06:00
MHDA- 2019/10/11 06:00
CRDT- 2019/09/03 06:00
PHST- 2019/09/03 06:00 [pubmed]
PHST- 2019/10/11 06:00 [medline]
PHST- 2019/09/03 06:00 [entrez]
AID - 10.1021/acs.jafc.9b04648 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2019 Sep 18;67(37):10513-10520. doi: 10.1021/acs.jafc.9b04648. 
      Epub 2019 Sep 10.