Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet.
BACKGROUND
Obesity is a risk factor for acute pancreatitis (AP), but the molecular mechanism remains unclear. Adiponectin, an adipose tissue-derived secretory factor, has anti-inflammatory properties in addition to various biological functions, and its plasma concentrations are reduced in obese subjects. However, the role of adiponectin in AP has not been investigated.


OBJECTIVE
To determine the effects of adiponectin on AP.


METHODS
We investigated the effects of adiponectin on experimental AP by using adiponectin-knockout (APN-KO) mice and adenovirus-mediated adiponectin over-expression. AP was induced by 10 hourly intraperitoneal injections of low-dose caerulein (10 microg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wild-type (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically.


RESULTS
Low-dose caerulein treatment did not induce pancreatic damage in either WT or APN-KO mice under normal chow feeding. APN-KO mice, but not WT mice, fed a HFD and then treated with caerulein developed pancreatic damage and inflammation, accompanied by increased macrophage/neutrophil infiltration and upregulation of pro-inflammatory mediators such as tumour necrosis factor alpha in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice.


CONCLUSIONS
Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.
Araki
H
H
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, K1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nishihara
T
T
Matsuda
M
M
Fukuhara
A
A
Kihara
S
S
Funahashi
T
T
Kataoka
T R
TR
Kamada
Y
Y
Kiyohara
T
T
Tamura
S
S
Hayashi
N
N
Shimomura
I
I
D000208:Acute Disease; D052242:Adiponectin / Q000378:metabolism / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002108:Ceruletide; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D052242:Adiponectin; D004041:Dietary Fats; D002108:Ceruletide