Obesity
is associated with gut microbiome dysbiosis. Our previous
research has shown that highly branched rhamnogalacturonan type I
(RG-I)-enriched pectin (WRP, 531.5 kDa, 70.44% RG-I, Rha/(Gal + Ara)
= 20) and its oligosaccharide with less branched RG-I [DWRP, 12.1
kDa, 50.29% RG-I, Rha/(Gal + Ara) = 6] are potential prebiotics. The
present study is conducted to uncover the impact of the content, molecular
size, and branch degrees of RG-I on the inhibiting effect of high-fat
diet (HFD)-induced obesity. The commercial pectin (CP, 496.2 kDa,
35.77% RG-I, Rha/(Gal + Ara) = 6), WRP, and DWRP were orally administered
to HFD-fed C57BL/6J mice (100 mg kg–1 d–1) to determine their individual effects on obesity. WRP significantly
prevented bodyweight gain, insulin resistance, and inflammatory responses
in HFD-fed mice. No obvious anti-obesity effect was observed in either
CP or DWRP supplementation. A mechanistic study revealed that CP and
DWRP could not enhance the diversity of gut microbiota, while WRP
treatment positively modulated the gut microbiota of obese mice by
increasing the abundance of Butyrivibrio, Roseburia, Barnesiella, Flavonifractor, Acetivibrio, and Clostridium cluster IV. Furthermore,
WRP significantly promoted browning of white adipose tissues in HFD-fed
mice, while CP and DWRP did not. WRP can attenuate the HFD-induced
obesity by modulation of gut microbiota and lipid metabolism. Highly
branched RG-I domain enrichment is essential for pectin mitigating
against the HFD-induced obesity.
ABSTRACT. Helicobacter pylori employs unique methods to colonize the stomach, which induces chronic inflammation. It is also able to avoid eradication by macrophages and other immune cells. Leukocyte cell-derived chemotaxin 2 (LECT2), a multi-functional cytokine involved in many pathological conditions, has recently been shown to activate macrophages via the CD209a receptor. Therefore, we aimed to investigate the effects of LECT2 on H. pylori-infected macrophages. Macrophages were treated with recombinant LECT2, and both their ability to kill H. pylori and produce nitric oxide were analyzed. Western blot was performed to determine nuclear translocation and protein phosphorylation of p65, a subunit of nuclear factor (NF)-kB. Transfection experiments were performed to analyze the signaling pathway of LECT2 in macrophages. We found that treatment with LECT2 enhanced H. pylori killing and nitric oxide production in macrophages. In addition, DNA-binding activity and nuclear translocation of p65 were up-regulated by LECT2 treatment. Furthermore, we found that NFkB activation by LECT2 was mediated by Raf-1 in macrophages, and Raf-1 phosphorylation was specifically altered in response to LECT2. Moreover, LECT2 induced Ser28 phosphorylation in the intracellular domain of CD209a. CD209a Ser28 phosphorylation was required for LECT2-induced Raf-1 and NF-kB activation in RAW264.7 macrophages. Our study showed that the effects of LECT2 on H. pylori killing and nitric oxide production were dependent on CD209a phosphorylation, Raf-1, and NF-kB activation. Together, these results demonstrate for the first time that exposure to LECT2 can modulate specific intracellular mechanisms downstream of CD209a to enhance H. pylori killing and nitric oxide production in macrophages.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.