高膳食铁在西方饮食喂养雄性大鼠中导致胰岛损伤和急性胰腺炎。

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.

Faculty of Veterinary Science, University of Sydney, Camperdown, Australia; Pre-Clinical Research Services and Education, The Canberra Hospital, Garran, Australia.

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

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.

背景

高膳食铁与 2 型糖尿病风险增加有关。我们之前已经表明，宫内发育受限（IUGR）和给予雄性斯普拉格-道利大鼠西方饮食（WD），无论是独立的还是联合的，都会导致胰岛炎症、纤维化和含铁血黄素沉着。

目的

研究铁是否在 IUGR 和 WD 摄入引起的这种炎症性胰岛损伤的发病机制中起作用。

方法

从断奶开始，用低铁（LI，20mg/kg）或高铁（HI，500mg/kg）喂养从双侧子宫动脉结扎（IUGR）和假手术（Sham）孕鼠分娩的雄性斯普拉格-道利（Sprague-Dawley）后代，寄养给未手术的孕鼠。研究了 4 组：Sham-LI、Sham-HI、IUGR-LI 和 IUGR-HI。记录大鼠体重、血糖、血脂和胰岛素的连续测量、腹腔葡萄糖耐量试验（13 周龄）以及胰腺和肝脏的组织学分析（14 周龄）。分析了铁、IUGR 及其相互作用对这些测量值的影响。

结果

与 LI 相比，WD 与 HI 一起导致 14 周龄时体重增加 11%（P<0.001），葡萄糖耐量受损[葡萄糖 AUC（G-AUC）升高 17%；P<0.001），急性胰腺炎（17/18，HI；6/17，LI；P<0.001），胰腺相关脂肪坏死和皂化（7/18，HI；0/17 LI；P<0.01），胰岛纤维化损伤趋势（7/18，HI；1/17 LI；P=0.051）。尽管几乎所有 WD 喂养的大鼠都有胰腺和肝脂肪变性，但只有 HI 喂养的大鼠有胰腺和肝脏铁积累（两者均 P<0.0001），肝脏铁积累较轻。IUGR 独立于膳食铁，也会导致葡萄糖耐量受损（G-AUC：升高 17%；P<0.05）。