Short-term high-fat feeding induces islet macrophage infiltration and ß-cell
replication independently of insulin resistance in mice.
Authors Woodland DC, Liu W, Leong J, Sears ML, Luo P, Chen X
Submitted By Submitted Externally on 3/23/2018
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2016
Date Published 10/1/2016
Volume : Pages 311 : E763 - E771
PubMed Reference 27577853
Abstract Short-term high-fat consumption stimulates mouse islet ß-cell replication
through unknown mechanisms. Resident macrophages (MFs) are capable of secreting
various factors involved in islet development and tissue remodeling. We
hypothesized that a short-term high-fat diet (HFD) promotes MF infiltration in
pancreatic islets and that MFs serve as a regulator of ß-cell replication. To
test these hypotheses and dissect mechanisms involved in HFD-induced ß-cell
replication, adult C57BL/6J mice were fed a HFD for 7 days with or without
administration of clodronate-containing liposomes, an MF-depleting agent. Mouse
body and epididymal fat pad weights, and nonfasting blood glucose and fasting
serum insulin levels were measured, and pancreatic islet ß-cell replication,
oxidative stress, and MF infiltration were examined. Short-term HFD promoted an
increase in body and epididymal fat pad weight and blood glucose levels, along
with an increased fasting serum insulin concentration. ß-Cell replication, islet
MF infiltration, and the percentage of inducible NO synthase positive MFs in the
islets increased significantly in mice fed the HFD. Immunofluorescence staining
for 8-oxo-2'-deoxyguanosine or activated caspase-3 revealed no significant
induction of DNA damage or apoptosis, respectively. In addition, no change in
stromal-derived factor 1-expressing cells was found induced by HFD. Despite
continuous elevation of nonfasting blood glucose and fasting serum insulin
levels, depletion of MFs through treatments of clodronate abrogated HFD-induced
ß-cell replication. These findings demonstrated that HFD-induced MF infiltration
is responsible for ß-cell replication. This study suggests the existence of
MF-mediated mechanisms in ß-cell replication that are independent of insulin
resistance.

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