PMID- 32583421
OWN - NLM
STAT- MEDLINE
DCOM- 20210827
LR  - 20240226
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 236
IP  - 1
DP  - 2021 Jan
TI  - Carbohydrate response element-binding protein regulates lipid metabolism via mTOR 
      complex1 in diabetic nephropathy.
PG  - 625-640
LID - 10.1002/jcp.29890 [doi]
AB  - Lipid deposition caused by the disorder of renal lipid metabolism is involved in 
      diabetic nephropathy (DN). Carbohydrate response element-binding protein (ChREBP) 
      is a key transcription factor in high glucose-induced cellular fat synthesis. At 
      present, the regulation and mechanism of ChREBP on fat metabolism in diabetic 
      kidneys are still unclear. In this study, we showed that lack of ChREBP 
      significantly improved renal injury, inhibited oxidative stress, lipid 
      deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and 
      thioredoxin-interacting protein (TXNIP) expression, as well as the activity of 
      mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys. Meanwhile, 
      ChREBP deficiency upregulated the expression of peroxisome proliferator-activated 
      receptor-alpha (PPARalpha), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme 
      A oxidase 1 (ACOX1) in diabetic kidneys. In vitro, knockdown of ChREBP attenuated 
      lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased 
      PPARalpha, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose 
      (HG) conditions. Moreover, HG-induced lipid deposition, increased expression of 
      FASN and ACC and decreased expression of PPARalpha, CPT1A, and ACOX1 were reversed by 
      rapamycin, a specific inhibitor of mTORC1, in HK-2 cells. These results indicate 
      that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by 
      inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential 
      therapeutic strategy to treat DN.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Chen, Nan
AU  - Chen N
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China.
FAU - Mu, Lin
AU  - Mu L
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China.
AD  - Department of Nephrology, Second Hospital, Hebei Medical University, 
      Shijiazhuang, China.
FAU - Yang, Zhifen
AU  - Yang Z
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
FAU - Du, Chunyang
AU  - Du C
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China.
FAU - Wu, Ming
AU  - Wu M
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
FAU - Song, Shan
AU  - Song S
AUID- ORCID: 0000-0002-2841-2213
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China.
FAU - Yuan, Chen
AU  - Yuan C
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
FAU - Shi, Yonghong
AU  - Shi Y
AUID- ORCID: 0000-0002-8920-6966
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200624
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Carrier Proteins)
RN  - 0 (MLXIPL protein, human)
RN  - 0 (PPAR alpha)
RN  - EC 1.3.3.6 (Acyl-CoA Oxidase)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Acyl-CoA Oxidase/metabolism
MH  - Animals
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism
MH  - Carnitine O-Palmitoyltransferase/metabolism
MH  - Carrier Proteins/metabolism
MH  - Cell Line
MH  - Diabetes Mellitus/metabolism
MH  - Diabetic Nephropathies/*metabolism
MH  - Fatty Acid Synthases/metabolism
MH  - Gene Expression Regulation/physiology
MH  - Glucose/metabolism
MH  - Humans
MH  - Kidney/metabolism
MH  - Lipid Metabolism/*physiology
MH  - Mechanistic Target of Rapamycin Complex 1/*metabolism
MH  - Mice, Knockout
MH  - PPAR alpha/metabolism
MH  - Podocytes/metabolism
MH  - Up-Regulation/physiology
MH  - Mice
OTO - NOTNLM
OT  - ChREBP
OT  - diabetic nephropathy
OT  - fatty acid oxidation
OT  - fatty acid synthesis
OT  - mTORC1
EDAT- 2020/06/26 06:00
MHDA- 2021/08/28 06:00
CRDT- 2020/06/26 06:00
PHST- 2020/02/14 00:00 [received]
PHST- 2020/06/09 00:00 [revised]
PHST- 2020/06/10 00:00 [accepted]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2021/08/28 06:00 [medline]
PHST- 2020/06/26 06:00 [entrez]
AID - 10.1002/jcp.29890 [doi]
PST - ppublish
SO  - J Cell Physiol. 2021 Jan;236(1):625-640. doi: 10.1002/jcp.29890. Epub 2020 Jun 
      24.