PMID- 38254294
OWN - NLM
STAT- MEDLINE
DCOM- 20240502
LR  - 20240505
IS  - 2093-5978 (Electronic)
IS  - 2093-596X (Print)
IS  - 2093-596X (Linking)
VI  - 39
IP  - 2
DP  - 2024 Apr
TI  - Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy 
      Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells.
PG  - 353-363
LID - 10.3803/EnM.2023.1809 [doi]
AB  - BACKGRUOUND: Polyunsaturated fatty acids (PUFAs) reportedly have protective 
      effects on pancreatic beta-cells; however, the underlying mechanisms are unknown. 
      METHODS: To investigate the cellular mechanism of PUFA-induced cell protection, 
      mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or 
      docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis 
      were examined. RESULTS: DHA treatment remarkably repressed caspase-3 cleavage and 
      terminal deoxynucleotidyl transferase-mediated UTP nick end labeling 
      (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of 
      autophagy, an increase in microtubule- associated protein 1-light chain 3 
      (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors 
      involved in autophagy regulation (Beclin-1, unc51 like autophagy activating 
      kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein 
      kinase B) were also altered by DHA treatment. DHA specifically induced 
      phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. 
      The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was 
      demonstrated using a GPR120 agonist and antagonist. Additional treatment with 
      AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and 
      protection. Taken together, DHA-induced autophagy activation with protection 
      against PA-induced apoptosis mediated by the GPR120/mTOR axis. CONCLUSION: These 
      findings indicate that DHA has therapeutic effects on PA-induced pancreatic 
      beta-cells, and that the cellular mechanism of beta-cell protection by DHA may be a new 
      research target with potential pharmacotherapeutic implications in beta-cell 
      protection.
FAU - Hong, Seok-Woo
AU  - Hong SW
AD  - Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
FAU - Lee, Jinmi
AU  - Lee J
AD  - Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
FAU - Moon, Sun Joon
AU  - Moon SJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Kwon, Hyemi
AU  - Kwon H
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Park, Se Eun
AU  - Park SE
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Rhee, Eun-Jung
AU  - Rhee EJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Lee, Won-Young
AU  - Lee WY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.
LA  - eng
GR  - 2021R1F1A1057306/National Research Foundation of Korea/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240123
PL  - Korea (South)
TA  - Endocrinol Metab (Seoul)
JT  - Endocrinology and metabolism (Seoul, Korea)
JID - 101554139
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (FFAR4 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - 0 (Palmitates)
RN  - 2V16EO95H1 (Palmitic Acid)
SB  - IM
MH  - Animals
MH  - *Autophagy/drug effects
MH  - Mice
MH  - *Apoptosis/drug effects
MH  - *TOR Serine-Threonine Kinases/metabolism
MH  - *Docosahexaenoic Acids/pharmacology
MH  - *Insulin-Secreting Cells/drug effects/metabolism
MH  - *Receptors, G-Protein-Coupled/metabolism
MH  - *Up-Regulation/drug effects
MH  - *Signal Transduction/drug effects
MH  - Palmitates/pharmacology
MH  - Palmitic Acid/pharmacology
PMC - PMC11066451
OTO - NOTNLM
OT  - Autophagy
OT  - Docosahexaenoic acids
OT  - G-protein-coupled receptor
OT  - Insulin-secreting cells
COIS- CONFLICTS OF INTEREST Won-Young Lee is an editor-in-chief and Eun-Jung Rhee is a 
      deputy editor of the journal. However, they were not involved in the peer 
      reviewer selection, evaluation, or decision process of this article. No other 
      potential conflicts of interest relevant to this article were reported.
EDAT- 2024/01/23 06:43
MHDA- 2024/05/02 06:42
PMCR- 2024/04/01
CRDT- 2024/01/23 00:21
PHST- 2023/08/21 00:00 [received]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2024/05/02 06:42 [medline]
PHST- 2024/01/23 06:43 [pubmed]
PHST- 2024/01/23 00:21 [entrez]
PHST- 2024/04/01 00:00 [pmc-release]
AID - EnM.2023.1809 [pii]
AID - enm-2023-1809 [pii]
AID - 10.3803/EnM.2023.1809 [doi]
PST - ppublish
SO  - Endocrinol Metab (Seoul). 2024 Apr;39(2):353-363. doi: 10.3803/EnM.2023.1809. 
      Epub 2024 Jan 23.