Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice.

Autor:	Woodland DC; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York; Department of Surgery, Columbia University Medical Center, New York, New York., Liu W; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York; Department of Surgery, Columbia University Medical Center, New York, New York; The Second Clinical Medicine College, Jilin University, Changchun, Jilin Province, China., Leong J; Touro College of Osteopathic Medicine, New York, New York; and., Sears ML; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York; Department of Surgery, Columbia University Medical Center, New York, New York., Luo P; The Second Clinical Medicine College, Jilin University, Changchun, Jilin Province, China., Chen X; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York; Department of Surgery, Columbia University Medical Center, New York, New York; xc2248@cumc.columbia.edu.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2016 Oct 01; Vol. 311 (4), pp. E763-E771. Date of Electronic Publication: 2016 Aug 30.
DOI:	10.1152/ajpendo.00092.2016
Abstrakt:	Short-term high-fat consumption stimulates mouse islet β-cell replication through unknown mechanisms. Resident macrophages (MΦs) are capable of secreting various factors involved in islet development and tissue remodeling. We hypothesized that a short-term high-fat diet (HFD) promotes MΦ infiltration in pancreatic islets and that MΦs serve as a regulator of β-cell replication. To test these hypotheses and dissect mechanisms involved in HFD-induced β-cell replication, adult C57BL/6J mice were fed a HFD for 7 days with or without administration of clodronate-containing liposomes, an MΦ-depleting agent. Mouse body and epididymal fat pad weights, and nonfasting blood glucose and fasting serum insulin levels were measured, and pancreatic islet β-cell replication, oxidative stress, and MΦ 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. β-Cell replication, islet MΦ infiltration, and the percentage of inducible NO synthase positive MΦs 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 MΦs through treatments of clodronate abrogated HFD-induced β-cell replication. These findings demonstrated that HFD-induced MΦ infiltration is responsible for β-cell replication. This study suggests the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance. (Copyright © 2016 the American Physiological Society.)
Databáze:	MEDLINE
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