Ojo Babajide A, Alake Sanmi E, Kaur Amritpal, Wong Siau Yen, Keirns Bryant, Ritchey Jerry W, Chowanadisai Winyoo, Lin Dingbo, Clarke Stephen, Smith Brenda J, Lucas Edralin A
Division of Pediatric Gastroenterology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Nutritional Sciences Department, Oklahoma State University, Stillwater, OK, USA.
Curr Dev Nutr. 2022 Dec 23;7(1):100023. doi: 10.1016/j.cdnut.2022.100023. eCollection 2023 Jan.
Commensal gut bacteria, including can produce metabolites that stimulate the release of gut antimicrobial peptides (AMPs) via the signal transducer and activator of transcription (STAT)3 pathway and prevent obesity-associated leaky gut and chronic inflammation. We have previously reported that wheat germ (WG) selectively increased cecal in obese mice.
This study investigated the effects of WG on gut STAT3 activation and AMPs (Reg3γ and Reg3β) as well as the potential of WG to inhibit nuclear Nf-κB-activation and immune cell infiltration in the visceral adipose tissue (VAT) of mice fed a Western diet (i.e., high-fat and sucrose diet [HFS]).
Six-wk-old male C57BL/6 mice were randomly assigned to 4 groups ( = 12/group): control (C, 10% fat and sucrose kcal) or HFS (45% fat and 26% sucrose kcal) diet with or without 10% WG (wt/wt) for 12 wk. Assessments include serum metabolic parameters jejunal AMPs genes, inflammatory markers, and phosphorylation of STAT3 as well as VAT NF-κBp65. Independent and interaction effects of HFS and WG were analyzed with a 2-factor ANOVA.
WG significantly improved markers of insulin resistance and upregulated jejunal and genes. The HFS + WG group had a 15-fold increase in jejunal pSTAT3 compared with the HFS group. Consequently, WG significantly upregulated jejunal mRNA expression of Reg3γ and Reg3β. The HFS group had a significantly higher VAT NF-κBp65 phosphorylation than the C group, while the HFS + WG group suppressed this to the level of C. Moreover, VAT and genes were downregulated in the HFS + WG group compared with HFS. Genes related to macrophage infiltration in the VAT were repressed in the WG-fed mice.
These findings show the potential of WG to influence vital regulatory pathways in the gut and adipose tissue which may reduce the chronic inflammatory burden on these tissues that are important targets in obesity and insulin resistance.
包括[具体细菌名称未给出]在内的肠道共生菌可产生代谢产物,通过信号转导及转录激活因子(STAT)3途径刺激肠道抗菌肽(AMP)释放,并预防肥胖相关的肠黏膜通透性增加和慢性炎症。我们之前报道过,小麦胚芽(WG)可选择性增加肥胖小鼠盲肠中的[具体物质未给出]。
本研究调查了WG对肠道STAT3激活及AMP(Reg3γ和Reg3β)的影响,以及WG抑制喂食西式饮食(即高脂肪和高蔗糖饮食[HFS])小鼠内脏脂肪组织(VAT)中核Nf-κB激活和免疫细胞浸润的潜力。
将6周龄雄性C57BL/6小鼠随机分为4组(每组n = 12):对照组(C,10%脂肪和蔗糖千卡)或HFS组(45%脂肪和26%蔗糖千卡),分别给予含或不含10% WG(重量/重量)的饲料,持续12周。评估指标包括血清代谢参数、空肠AMP基因、炎症标志物、STAT3磷酸化水平以及VAT中NF-κBp65。采用双因素方差分析分析HFS和WG的独立及交互作用。
WG显著改善胰岛素抵抗指标,并上调空肠Reg3γ和Reg3β基因。与HFS组相比,HFS + WG组空肠pSTAT3增加了15倍。因此,WG显著上调空肠Reg3γ和Reg3β的mRNA表达。HFS组VAT中NF-κBp65磷酸化水平显著高于C组,而HFS + WG组将其抑制至C组水平。此外,与HFS组相比,HFS + WG组VAT中[具体基因未给出]和[具体基因未给出]基因下调。在喂食WG的小鼠中,与VAT中巨噬细胞浸润相关的基因受到抑制。
这些发现表明,WG有可能影响肠道和脂肪组织中的重要调节途径,这可能会减轻这些组织上的慢性炎症负担,而这些组织是肥胖和胰岛素抵抗的重要靶点。