Milk Fat Globule Membrane Alleviates Short Bowel Syndrome-Associated Liver Injury in Rats Through Inhibiting Autophagy and NLRP3 Inflammasome Activation.

Zhicai Yu,Honghao Chen,Yang Niu,Shanshan Huang,Jiang Wu,Ying Li

doi:10.3389/fnut.2022.758762

Abstract

BackgroundThe milk fat globule membrane (MFGM), a tri-layer membrane structure surrounding the milk fat globule, has been shown to have immune-modulating properties. This study aimed to investigate the effects of MFGM supplementation in a rat model of short bowel syndrome (SBS) associated liver disease and its possible mechanisms.Materials and MethodsTwenty one male Sprague-Dawley rats were randomly divided into three groups: Sham, SBS (underwent massive small bowel resection), and SBS+MFGM (SBS rats supplemented with 1.5 g/kg/d MFGM). Liver pathology, myeloperoxidase (MPO) staining, serum levels of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), endotoxin concentration, protein expression of autophagy and nucleotide binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) pathway in the liver tissue were measured.ResultsBoth SBS and SBS + MFGM groups had higher serum levels of ALT and liver endotoxin levels than the Sham group (P < 0.05), with no difference detected between each other. Compared with the SBS group, the SBS+MFGM group showed lower liver pathology scores of steatosis and inflammation, less MPO positive cells and reduced expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β(P < 0.05) in the liver. Additionally, the expression of Beclin-1 and microtubule-associated protein1 light chain 3(LC3) B, the fluorescence intensity of NLRP3 and LC3B in the SBS + MFGM group were lower than the SBS group (P < 0.05). The LC3B expression was positively correlated with the NLRP3 level.ConclusionEnteral supplementation of MFGM help to alleviate liver injury in SBS rats, which might be related to inhibition of aberrant activation of autophagy and NLRP3 inflammasome pathways.

Highlights

Short bowel syndrome-associated liver disease (SBS-ALD) is one of the most common complications in patients with short bowel syndrome (SBS), which might progress to severe liver injuries such as fibrosis or even end-stage liver diseases [1]
On post-operation day 15, the body weights of the Sham (245.28 ± 15.07g) group were higher than both the SBS (206.14 ± 25.98 g) and SBS + milk fat globule membrane (MFGM) (205.00 ± 29.82 g) groups
Compared with the Sham group, liver histology changes in the SBS group were characterized by steatosis and hepatocyte ballooning, and inflammatory cell infiltration in the portal area

Summary

Introduction

Short bowel syndrome-associated liver disease (SBS-ALD) is one of the most common complications in patients with short bowel syndrome (SBS), which might progress to severe liver injuries such as fibrosis or even end-stage liver diseases [1]. Studies indicated that small bowel resection (SBR) itself was a key contributing factor for liver injuries [5, 6]. Several lines of evidence have highlighted the pivotal role of leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome in liver diseases, such as viral hepatitis and sterile inflammatory liver injury [7, 8]. Another study showed that pretreating HSC-T6 hepatic stellate cells with 3-methyladenine (3-MA), an autophagy inhibitor, decreased the protein expression of NLRP3 and IL-1β, thereby attenuated the NaAsO2-induced liver damage [14]. The changes in autophagy and the NLRP3 inflammasome pathway in the progression of liver injury in SBS setting still remains to be explored. This study aimed to investigate the effects of MFGM supplementation in a rat model of short bowel syndrome (SBS) associated liver disease and its possible mechanisms

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Conclusion