PMID- 29352300
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181202
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 1
DP  - 2018
TI  - 5-aminosalicylic acid improves lipid profile in mice fed a high-fat cholesterol 
      diet through its dual effects on intestinal PPARgamma and PPARalpha.
PG  - e0191485
LID - 10.1371/journal.pone.0191485 [doi]
LID - e0191485
AB  - Obesity is associated with a series of metabolic complications, including 
      dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent 
      years, intestinal inflammation has been suggested to contribute to obesity 
      related metabolic syndrome and targeting gut inflammation with 5-ASA improves 
      diet induced IR, however, its role in dyslipidemia is unknown and has never been 
      explored. In the present study, we reported for the first time that 
      administration of 5-ASA for 12 weeks significantly improved lipid profile by 
      repressing plasma triglycerides and free cholesterol levels in mice fed high-fat 
      cholesterol diet (HFC). In addition, liver lipids were significantly reduced by 
      5-ASA treatment in HFC-fed mice. Mechanistically, anti-inflammatory genes 
      peroxisome proliferator-activated receptor-gamma (Ppargamma) and M2 marker, such as Mrc1 
      and Ym1, were remarkably upregulated, while pro-inflammation gene monocyte 
      chemoattractant protein-1 (Mcp-1) were downregulated in small intestine of mice 
      treated by 5-ASA. Further, 5-ASA improved gastrointestinal barrier by increasing 
      the expression of the tight junction marker ZO-1. 5-ASA also enhanced cholesterol 
      translocation by elevating genes expression of Npc1l1 and Abcg5/8. Moreover, mice 
      fed HFC 5-ASA expressed increased Pparalpha in small intestinal and its target genes 
      function in lipid oxidation and hydrolysis were remarkable elevated. Taken 
      together, we reported a novel role of 5-ASA which may serve as a therapy target 
      intestinal inflammation induced dyslipidemia.
FAU - Wang, Zheng
AU  - Wang Z
AUID- ORCID: 0000-0001-8593-0669
AD  - Department of Geriatrics and Gastroenterology, Huadong Hospital, Shanghai Medical 
      College, Fudan University, Shanghai Key Laboratory of Clinical Geriatric 
      Medicine, Shanghai, P.R. China.
AD  - Department of Pediatrics, Section Molecular Genetics, University Medical Center 
      Groningen, University of Groningen, Groningen, the Netherlands.
FAU - Koonen, Debby
AU  - Koonen D
AD  - Department of Pediatrics, Section Molecular Genetics, University Medical Center 
      Groningen, University of Groningen, Groningen, the Netherlands.
FAU - Hofker, Marten
AU  - Hofker M
AD  - Department of Pediatrics, Section Molecular Genetics, University Medical Center 
      Groningen, University of Groningen, Groningen, the Netherlands.
FAU - Bao, Zhijun
AU  - Bao Z
AD  - Department of Geriatrics and Gastroenterology, Huadong Hospital, Shanghai Medical 
      College, Fudan University, Shanghai Key Laboratory of Clinical Geriatric 
      Medicine, Shanghai, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20180119
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Fatty Acids)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Lipids)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 4Q81I59GXC (Mesalamine)
SB  - IM
RIN - PLoS One. 2018 Jul 12;13(7):e0200947. PMID: 30001434
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Cholesterol, Dietary/*administration & dosage
MH  - Diet, High-Fat/*adverse effects
MH  - Dyslipidemias/drug therapy/genetics/metabolism
MH  - Fatty Acids/metabolism
MH  - Hypolipidemic Agents/pharmacology
MH  - Inflammation/drug therapy/genetics/metabolism
MH  - Intestinal Mucosa/*metabolism
MH  - Intestines/*drug effects
MH  - Lipid Metabolism/*drug effects/genetics
MH  - Lipids/blood
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mesalamine/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PPAR alpha/*metabolism
MH  - PPAR gamma/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC5774772
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/01/21 06:00
MHDA- 2018/02/27 06:00
PMCR- 2018/01/19
CRDT- 2018/01/21 06:00
PHST- 2017/04/25 00:00 [received]
PHST- 2018/01/07 00:00 [accepted]
PHST- 2018/01/21 06:00 [entrez]
PHST- 2018/01/21 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2018/01/19 00:00 [pmc-release]
AID - PONE-D-17-15953 [pii]
AID - 10.1371/journal.pone.0191485 [doi]
PST - epublish
SO  - PLoS One. 2018 Jan 19;13(1):e0191485. doi: 10.1371/journal.pone.0191485. 
      eCollection 2018.