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Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Adiponectin is recognized as an antiinflammatory and antifibrotic protein derived from adipocytes, and low serum adiponectin levels are present in obesity. Recent studies have highlighted the relationship between obesity and pancreatic diseases. However, the role of adiponectin in chronic pancreatitis remains uncertain. The aim of this study was to determine the effects of adiponectin in chronic pancreatitis.

Methods

We investigated the effects of adiponectin in experimental chronic pancreatitis by using adiponectin-knockout (APN-KO) mice. Chronic pancreatitis was induced by repeated hourly (6 times) intraperitoneal injections of 50 µg/kg cerulein three times per week for 4 weeks in wild-type (WT) and APN-KO mice. We evaluated the severity of chronic pancreatitis biochemically and morphologically.

Results

In cerulein-treated mice, macroscopically and histologically, severe pancreatic damage was observed in APN-KO mice compared with findings in WT mice. The histological scores for chronic pancreatitis, including glandular atrophy, pseudotubular complex, fibrosis, and total scores, were significantly higher in APN-KO mice than in WT mice. Activated pancreatic stellate cells and F4/80-positive pancreatic macrophages accumulated in the pancreas of APN-KO mice but not in WT mice. Overexpression of the mRNAs of transforming growth factor-β1, CD68, and monocyte chemoattractant protein-1 was noted in APN-KO mice but not in WT mice. The gene expression level of collagen1 (α1) tended to be higher in APN-KO mice than in WT mice, albeit insignificantly.

Conclusions

Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice. Hypoadiponectinemia could enhance the severity of chronic pancreatitis.

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Abbreviations

α-SMA:

α-Smooth muscle actin

AMPK:

AMP-activated protein kinase

APN-KO:

Adiponectin knockout

BMI:

Body mass index

DBTC:

Dibutyltin dichloride

ECM:

Extracellular matrix

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HSCs:

Hepatic stellate cells

MCP-1:

Monocyte chemoattractant protein-1

NASH:

Nonalcoholic steatohepatitis

PPARα:

Peroxisome proliferator activated receptor-α

PSCs:

Pancreatic stellate cells

RT-PCR:

Reverse transcription-polymerase chain reaction

TGF-β1:

Transforming growth factor-β1

TNF-α:

Tumor necrosis factor-α

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, 2-2, K1, Yamada-oka, Suita, Osaka, 565-0871, Japan

    Takuya Yamada, Hiroshi Araki, Kenji Watabe, Yoshihiro Kamada, Shinichi Kiso, Hideharu Ogiyama, Shusaku Tsutsui & Norio Hayashi

  2. Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, 13-9, Rokutanji-cho, Nishinomiya, Hyogo, 662-0918, Japan

    Tamao Nishihara

  3. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, Osaka, 565-0871, Japan

    Shinji Kihara, Tohru Funahashi & Iichiro Shimomura

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  1. Takuya Yamada
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  2. Hiroshi Araki
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  3. Kenji Watabe
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  4. Yoshihiro Kamada
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Correspondence to Shusaku Tsutsui.

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Yamada, T., Araki, H., Watabe, K. et al. Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice. J Gastroenterol 45, 742–749 (2010). https://doi.org/10.1007/s00535-010-0205-9

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  • DOI: https://doi.org/10.1007/s00535-010-0205-9

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