PMID- 25647410
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 35
IP  - 4
DP  - 2015 Apr
TI  - Palmitate induces endoplasmic reticulum stress and autophagy in mature 
      adipocytes: implications for apoptosis and inflammation.
PG  - 932-40
LID - 10.3892/ijmm.2015.2085 [doi]
AB  - Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to 
      adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies 
      have indicated that understanding the physiological role of autophagy is of great 
      significance. In the present study, an in vitro model was used in which 3T3-L1 
      adipocytes were pre-loaded with palmitate (PA) to generate artificially 
      hypertrophied mature adipocytes. PA induced an autophagic flux, determined by an 
      increased microtubule-associated protein 1 light chain 3 (LC3)-II formation, as 
      shown by western blot analysis and fluorescence microscopy, and was confirmed 
      using transmission electron microscopy (TEM). Using TEM and western blot 
      analysis, we observed increased ER stress in response to PA, as indicated by the 
      increased levels of the ER stress markers, BiP, activating transcription factor 4 
      (ATF4) and C/EBP homologous protein (CHOP), and the phosphoralytion of eukaryotic 
      translation initiation factor 2alpha and c-Jun N-terminal kinase (JNK). Of note, we 
      observed that the PA-induced ER stress occurred prior to the activation of 
      autophagy. We confirmed that autophagy was induced in response to JNK-dependent 
      ER stress, as autophagy was suppressed by treatment with the ER stress inhibitor, 
      4-phenyl butyrate (4-PBA), and the JNK inhibitor, SP600125. Upon the inhibition 
      of autophagy using chloroquine (CQ), we observed exacerbated ER stress and an 
      increased level of cell death. Importantly, to determine whether autophagy is 
      linked to inflammation, the autophagy inhibitor, 3-methyladenine (3-MA) was used. 
      The inhibition of autophagy led to a further increase in the PA-induced 
      expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 
      (IL-6). Consistently, such an increase was also observed following treatment with 
      SP600125. In conclusion, our data indicate that PA elicits a ER 
      stress-JNK-autophagy axis, and that this confers a pro-survival effect against 
      PA-induced cell death and stress in hypertrophied adipocytes. The JNK-dependent 
      activation of autophagy diminishes PA-induced inflammation. Therefore, the 
      stimulation of autophagy may become a method with which to attenuate adipocyte 
      dysfunction and inflammation.
FAU - Yin, Jiajing
AU  - Yin J
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
FAU - Wang, Yufan
AU  - Wang Y
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
FAU - Gu, Liping
AU  - Gu L
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
FAU - Fan, Nengguang
AU  - Fan N
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
FAU - Ma, Yuhang
AU  - Ma Y
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
FAU - Peng, Yongde
AU  - Peng Y
AD  - Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200080, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150130
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Cytokines)
RN  - 0 (Palmitates)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/*metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cytokines/genetics/metabolism
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Inflammation/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Mice
MH  - Palmitates/*pharmacology
PMC - PMC4356450
EDAT- 2015/02/04 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/01/30
CRDT- 2015/02/04 06:00
PHST- 2014/11/08 00:00 [received]
PHST- 2015/01/19 00:00 [accepted]
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/01/30 00:00 [pmc-release]
AID - ijmm-35-04-0932 [pii]
AID - 10.3892/ijmm.2015.2085 [doi]
PST - ppublish
SO  - Int J Mol Med. 2015 Apr;35(4):932-40. doi: 10.3892/ijmm.2015.2085. Epub 2015 Jan 
      30.