PMID- 25325265
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150106
LR  - 20211021
IS  - 2093-596X (Print)
IS  - 2093-5978 (Electronic)
IS  - 2093-596X (Linking)
VI  - 29
IP  - 4
DP  - 2014 Dec 29
TI  - Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis 
      Factor-alpha-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes.
PG  - 553-60
LID - 10.3803/EnM.2014.29.4.553 [doi]
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha and AMP-activated protein kinase (AMPK) 
      are known to stimulate and repress lipolysis in adipocytes, respectively; 
      however, the mechanisms regulating these processes have not been completely 
      elucidated. METHODS: The key factors and mechanism of action of TNF-alpha and AMPK in 
      lipolysis were investigated by evaluating perilipin expression and activity of 
      protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation 
      factor 2 alpha (eIF2alpha) by Western blot and an immunofluorescence assay in 24-hour 
      TNF-alpha-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation. 
      RESULTS: Enhancement of AMPK activity by the addition of activator minoimidazole 
      carboxamide ribonucleotide (AICAR) suppressed TNF-alpha-induced lipolysis, whereas 
      the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced 
      lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-alpha 
      and recovered following treatment with AICAR, showing a correlation with the 
      antilipolytic effect of AICAR. Significant activation of PERK/eIF2alpha, a component 
      of the unfolded protein response signaling pathway, was observed in TNF-alpha or 
      vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of 
      perilipin expression by AICAR in TNF-alpha-treated 3T3-L1 adipocytes were 
      significantly diminished by treatment with 2-aminopurine, a specific inhibitor of 
      eIF2alpha. CONCLUSION: These data indicated that AICAR-induced AMPK activation 
      attenuates TNF-alpha-induced lipolysis via preservation of perilipin in 3T3-L1 
      adipocytes. In addition, PERK/eIF2alpha activity is a novel mechanism of the 
      anti-lipolytic effect of AICAR.
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 - 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 - Park, Cheol Young
AU  - Park CY
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Oh, Ki Won
AU  - Oh KW
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 
      Korea.
FAU - Park, Sung Woo
AU  - Park SW
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. drlwy@hanmail.net.
LA  - eng
PT  - Journal Article
DEP - 20140527
PL  - Korea (South)
TA  - Endocrinol Metab (Seoul)
JT  - Endocrinology and metabolism (Seoul, Korea)
JID - 101554139
PMC - PMC4285046
OTO - NOTNLM
OT  - AMP-activated protein kinases
OT  - Adipocytes
OT  - Lipolysis
OT  - PERK/eIF2alpha
OT  - Perilipin
COIS- This work was supported by a grant from Chon Kun Dang Pharm (S-2013-0227-000). 
      However the design and interpretation of the work are independent of the funding.
EDAT- 2014/10/18 06:00
MHDA- 2014/10/18 06:01
PMCR- 2014/12/01
CRDT- 2014/10/18 06:00
PHST- 2014/02/27 00:00 [received]
PHST- 2014/04/11 00:00 [revised]
PHST- 2014/04/24 00:00 [accepted]
PHST- 2014/10/18 06:00 [entrez]
PHST- 2014/10/18 06:00 [pubmed]
PHST- 2014/10/18 06:01 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 29.e18 [pii]
AID - 10.3803/EnM.2014.29.4.553 [doi]
PST - ppublish
SO  - Endocrinol Metab (Seoul). 2014 Dec 29;29(4):553-60. doi: 
      10.3803/EnM.2014.29.4.553. Epub 2014 May 27.