PMID- 28599253
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20180501
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 49
DP  - 2017 Aug
TI  - Alantolactone improves palmitate-induced glucose intolerance and inflammation in 
      both lean and obese states in vitro: Adipocyte and adipocyte-macrophage 
      co-culture system.
PG  - 187-194
LID - S1567-5769(17)30219-9 [pii]
LID - 10.1016/j.intimp.2017.05.037 [doi]
AB  - Obesity is characterized by a massive infiltration of the adipose tissue by 
      macrophages. Adipocytes, together with macrophages create a crosstalk between 
      inflammation and insulin resistance. Excess saturated FFA, such as palmitate, 
      absorbed via the portal system may cause glucose intolerance and inflammation, 
      which leads to insulin resistance. In this study, we aimed to evaluate the 
      potency of alantolactone (AL), a sesquiterpene lactone isolated from Inula 
      helenium in reducing palmitate-induced glucose intolerance, fat accumulation, and 
      inflammation in 3T3-L1 adipocytes and adipocyte-macrophage co-culture system 
      (3T3-L1-RAW264.7). We observed that palmitate reduced glucose uptake and 
      increased fat accumulation, which indicated dysfunctional adipocytes with 
      inadequate lipid storage. However, AL treatment reversed these changes in a 
      dose-dependent manner (P<0.05). Palmitate activated c-Jun N-terminal kinases 
      (JNK) and IkappaB kinase beta/alpha (IKKbeta/alpha) phosphorylation, and increased the levels of 
      the proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6 [IL-6]) 
      and chemokines (monocyte chemoattractant protein-1 [MCP-1]). AL treatment 
      selectively reduced JNK-associated mitogen-activated protein kinase pathway (JNK 
      and extracellular signal-regulated kinase phosphorylation). However, it did not 
      affect NF-kappaB pathway in adipocytes. In addition, AL decreased the gene expression 
      of JNK upregulating factor, toll-like receptor-4 (TLR4), suggesting inhibition of 
      TLR4-JNK signaling. Moreover, it reduced inflammation-associated IL-6 and MCP-1 
      mRNA levels in both adipocytes and adipocyte-macrophage system. Our study showed 
      that palmitate treatment led to adipocyte dysfunction and macrophage 
      infiltration; however, AL improved palmitate-induced glucose intolerance and 
      inflammation. These findings suggest that AL may inhibit obesity-induced insulin 
      resistance and improve glucose homeostasis and inflammation in insulin target 
      tissues.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Kim, Minjee
AU  - Kim M
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul 08826, Republic of Korea.
FAU - Song, Kwangho
AU  - Song K
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul 08826, Republic of Korea.
FAU - Kim, Yeong Shik
AU  - Kim YS
AD  - Natural Products Research Institute, College of Pharmacy, Seoul National 
      University, Seoul 08826, Republic of Korea. Electronic address: kims@snu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20170607
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lactones)
RN  - 0 (Palmitates)
RN  - 0 (Sesquiterpenes, Eudesmane)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - M7GSN5Q1M6 (alantolactone)
SB  - IM
MH  - Adipocytes/*physiology
MH  - Animals
MH  - Antioxidants/*therapeutic use
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Glucose Intolerance/chemically induced/complications/*drug therapy
MH  - Inflammation/chemically induced/complications/*drug therapy
MH  - Inflammation Mediators/metabolism
MH  - Inula/immunology
MH  - Lactones/*therapeutic use
MH  - MAP Kinase Kinase 4/metabolism
MH  - MAP Kinase Signaling System
MH  - Macrophages/*physiology
MH  - Mice
MH  - Obesity/complications/*drug therapy
MH  - Palmitates
MH  - RAW 264.7 Cells
MH  - Sesquiterpenes, Eudesmane/*therapeutic use
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - Alantolactone
OT  - Diabetes
OT  - Glucose intolerance
OT  - Inflammation
OT  - Insulin resistance
OT  - Obesity
OT  - Palmitate
EDAT- 2017/06/10 06:00
MHDA- 2018/05/02 06:00
CRDT- 2017/06/10 06:00
PHST- 2017/03/03 00:00 [received]
PHST- 2017/05/29 00:00 [revised]
PHST- 2017/05/31 00:00 [accepted]
PHST- 2017/06/10 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/06/10 06:00 [entrez]
AID - S1567-5769(17)30219-9 [pii]
AID - 10.1016/j.intimp.2017.05.037 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2017 Aug;49:187-194. doi: 10.1016/j.intimp.2017.05.037. Epub 
      2017 Jun 7.