High Dietary Iron in Western Diet-Fed Male Rats Causes Pancreatic Islet Injury and Acute Pancreatitis

Viviane Delghingaro-Augusto; Ayumi Hosaka; Suzanne Estaphan; Alice Richardson; Jane E Dahlstrom; Christopher J Nolan

doi:10.1016/j.tjnut.2023.01.009

High Dietary Iron in Western Diet-Fed Male Rats Causes Pancreatic Islet Injury and Acute Pancreatitis

J Nutr. 2023 Mar;153(3):723-732. doi: 10.1016/j.tjnut.2023.01.009. Epub 2023 Jan 11.

Authors

Viviane Delghingaro-Augusto¹, Ayumi Hosaka², Suzanne Estaphan³, Alice Richardson⁴, Jane E Dahlstrom⁵, Christopher J Nolan⁶

Affiliations

¹ Australian National University Medical School, Australian National University, Canberra, Australia; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia. Electronic address: viviane.augusto@anu.edu.au.
² Faculty of Veterinary Science, University of Sydney, Camperdown, Australia; Pre-Clinical Research Services and Education, The Canberra Hospital, Garran, Australia.
³ Australian National University Medical School, Australian National University, Canberra, Australia.
⁴ Statistical Support Network, Australian National University, Canberra, Australia.
⁵ Australian National University Medical School, Australian National University, Canberra, Australia; Department of Anatomical Pathology, ACT Pathology, The Canberra Hospital, Australia.
⁶ Australian National University Medical School, Australian National University, Canberra, Australia; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia; Department of Endocrinology, The Canberra Hospital, Garran, Australia.

PMID: 36931751
DOI: 10.1016/j.tjnut.2023.01.009

Abstract

Background: High dietary iron has been linked to an increased type 2 diabetes risk. We have previously shown that intrauterine growth restriction (IUGR) and feeding a Western diet (WD) to male Sprague-Dawley rats independently, as well as together, cause pancreatic islet inflammation, fibrosis, and hemosiderosis.

Objectives: To investigate whether iron has a role in the pathogenesis of this inflammatory islet injury caused by IUGR and WD intake.

Methods: Male Sprague-Dawley offspring of bilateral uterine artery ligated (IUGR) and sham-operated (Sham) dams, fostered to nonoperated dams, were fed a WD [45% sucrose, 19.4% protein and 23% fat (w/w)] containing low iron (LI, 20 mg/kg) or high iron (HI, 500 mg/kg) from weaning. Four groups were studied: Sham-LI, Sham-HI, IUGR-LI, and IUGR-HI. Serial measurements of rat body weight, blood glucose, lipids and insulin, an intraperitoneal glucose tolerance test (age 13 wk), and histological analysis of pancreas and liver (age 14 wk) were recorded. The effects of iron, IUGR, and their interaction, on these measurements have been analyzed.

Results: WD with HI compared with LI caused an 11% greater weight gain by age 14 wk (P < 0.001), impaired glucose tolerance [AUC for glucose (G-AUC) 17% higher; P < 0.001), acute pancreatitis (17/18, HI; 6/17, LI; P < 0.001), pancreas-associated fat necrosis and saponification (7/18, HI; 0/17 LI; P < 0.01), and a trend to islet fibrotic injury (7/18, HI; 1/17 LI; P = 0.051). Although pancreatic and hepatic steatosis was evident in almost all WD-fed rats, pancreatic and hepatic iron accumulation was prevalent only in HI-fed rats (P < 0.0001 for both), being only mild in the livers. IUGR, independent of dietary iron, also caused impairment in glucose tolerance (G-AUC: 17% higher; P < 0.05).

Conclusions: A postweaning WD containing HI, independent of IUGR, causes acute pancreatitis and islet injury in Sprague-Dawley rats suggesting a role of dietary iron in the development of steatopancreatitis.

Keywords: Sprague-Dawley rat; dietary iron; intrauterine growth restriction; pancreatic islet; pancreatitis; type 2 diabetes; western diet.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Animals
Diabetes Mellitus, Type 2* / metabolism
Diet, Western
Female
Fetal Growth Retardation / metabolism
Glucose / metabolism
Humans
Iron / metabolism
Iron, Dietary
Islets of Langerhans* / metabolism
Male
Pancreatitis* / etiology
Pancreatitis* / metabolism
Rats
Rats, Sprague-Dawley

Substances

Iron, Dietary
Glucose
Iron