Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer.
OBJECTIVE
Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high-fat, high-calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study, we aimed to investigate the effects of an HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots.


METHODS
We examined the weight and visceral obesity in both wild-type and KC mice on either control diet (CD) or HFCD. After 3 months, mice were killed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots.


RESULTS
Both wild-type and KC mice on an HFCD exhibited significantly increased inflammation in the visceral adipose tissue, particularly in the peripancreatic fat (PPF), compared with animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots and between mice on the HFCD and CD.


CONCLUSIONS
Our results clearly demonstrate that an HFCD leads to obesity and inflammation in the visceral adipose tissue, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mice.
From the Departments of *Surgery and †Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA, Los Angeles, CA; and ‡Department of Biostatistics, Fielding School of Public Health at UCLA, Los Angeles, CA.
Kathleen M
KM
Hertzer
Mu
M
Xu
Aune
A
Moro
David W
DW
Dawson
Lin
L
Du
Gang
G
Li
Hui-Hua
HH
Chang
Alexander P
AP
Stark
Xiaoman
X
Jung
Oscar Joe
OJ
Hines
Guido
G
Eibl
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
D016207:Cytokines; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)