Dataset Information

Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice.

ABSTRACT: Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many health benefits. The aim of the current study was to investigate whether MFGM could prevent obesity through inhibiting adipogenesis and promoting brown remodeling of white adipose tissue (WAT) in mice fed with high-fat diet. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD plus MFGM at 100 mg/kg BW, 200 mg/kg BW or 400 mg/kg BW for 8 weeks. Results showed that MFGM suppressed body weight gain induced by HFD, reduced white adipose tissue (WAT) mass accompanied with the decrease in adipocyte sizes. MFGM was found to have partially improved serum lipid profiles, as well as to have suppressed HFD-induced adipogenesis as shown by reduced expression of peroxisome proliferators-activator receptor-? (PPAR?), CCAAT/enhancer-binding protein-? (C/EBP?) and sterol regulatory element-binding protein-1c (SREBP-1c). MFGM also markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), showing activation of AMPK pathway. Moreover, MFGM promoted browning of inguinal WAT by upregulation the protein expression of uncoupling protein 1 (UCP1) in HFD mice. Taken together, these findings provide evidence that MFGM may protect against diet-induced adiposity by suppressing adipogenesis and promoting brown-like transformation in WAT.

SUBMITTER: Li T

PROVIDER: S-EPMC5872749 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice.

Li Tiange T Gao Jing J Du Min M Song Jiajia J Mao Xueying X

Nutrients 20180309 3

Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many health benefits. The aim of the current study was to investigate whether MFGM could prevent obesity through inhibiting adipogenesis and promoting brown remodeling of white adipose tissue (WAT) in mice fed with high-fat diet. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD plus MFGM at 100 mg/kg BW, 200 mg/kg BW or 400 mg/kg BW for 8 weeks. Results showed that MFGM suppresse ...[more]

PMID: 29522452

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Project description:BACKGROUND:Acute kidney injury (AKI) is most commonly caused by sepsis in critically ill patients, and it is associated with high morbidity and mortality. The pathophysiology of sepsis-induced AKI is generally accepted to include direct inflammatory injury, endothelial cell dysfunction, and apoptosis. Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in the enhancement of apoptotic cell clearance and regulation of inflammation. We hypothesize that administration of recombinant mouse MFG-E8 (rmMFG-E8) can protect mice from kidney injuries caused by sepsis. METHODS:Sepsis was induced in 8-wk-old male C57BL/6 mice by cecal ligation and puncture (CLP). rmMFG-E8 or phosphate-buffered saline (vehicle) was injected intravenously at a dosage of 20 ?g/kg body weight at time of CLP (n = 5-8 mice per group). After 20 h, serum and renal tissue were harvested for various analyses. The renal injury markers blood urea nitrogen (BUN) and creatinine were determined by enzymatic and chemical reactions, respectively. The gene expression analysis was carried out by real-time quantitative polymerase chain reaction. RESULTS:At 20 h after CLP, serum levels of BUN and creatinine were both significantly increased in the vehicle group compared with the sham group, whereas the mice treated with rmMFG-E8 had a significant reduction in BUN and creatinine levels by 28% and 24.1%, respectively (BUN: 197.7 ± 23.6 versus 142.3 ± 20.7 mg/dL; creatinine: 0.83 ± 0.12 versus 0.63 ± 0.06 mg/dL; P < 0.05). Expressions of novel biomarkers of renal tissue injury neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 were also significantly downregulated by 58.2% and 95%, respectively, after treatment with rmMFG-E8. Proinflammatory cytokine interleukin-6 and tumor necrosis factor-? messenger RNA (mRNA) were significantly reduced by 50.8% and 50.3%, respectively, in rmMFG-E8-treated mice compared with vehicle-treated mice. The mRNA levels of the chemokines keratinocyte chemoattractant and macrophage inhibitory protein-2 were reduced by 85.1% and 78%, respectively, in mice treated with rmMFG-E8 compared with the vehicle mice. In addition, the expression of intercellular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) mRNA was downregulated by 35.6% and 77.8%, respectively, in rmMFG-E8-treated mice compared with the vehicle animals (P < 0.05). CONCLUSIONS:Treatment with rmMFG-E8 reduces renal tissue injury induced by sepsis through inhibiting the production of proinflammatory cytokines and chemokine, as well as through the activation of endothelial cells. Thus, MFG-E8 may have a therapeutic potential for treating AKI induced by sepsis.

Project description:ObjectiveInflammatory bowel disease (IBD) often occurs along with extraintestinal manifestations, including hepatic injury. Milk fat globule membrane (MFGM) is an active substance with a potential anti-inflammation activity. However, its alleviated effect and mechanisms in IBD as well as the IBD-induced secondary liver injury are still unclear.MethodsC57BL/6J mice were administered with a 21-day oral gavage of MFGM, followed by 7 days of drinking water with 4% dextran sulfate sodium (DSS). Disease activity index (DAI), histological features, and cytokines of the colon and liver were evaluated. Then, RNA-seq of the colon and liver was conducted. The gut microbiota was assessed by analyzing 16S rRNA gene sequences, and finally the integrity and the function of the mucus barrier were evaluated by Alcian blue staining, real-time quantitative PCR, and ELISA.ResultsProphylactic MFGM treatment was effective against colitis to include effects in body weight loss, DAI score, colonic length, intestinal pathology, and histological score. Additionally, prophylactic MFGM decreased the levels of interleukin (IL)-1β, IL-6, and myeloperoxidase in colonic tissue, while it increased the IL-10 level. Moreover, the gene expressions of MUC2, MUC4, Reg3b, and Reg3g associated with the production of the molecular mediator of immune response, membrane invagination, and response to protozoan were strikingly upregulated when administered with MFGM. On the other hand, the beneficial effects of MFGM were related to the enriched abundance of genera such as Faccalibacumum and Roseburia in feces samples. Consistently, the administration of MFGM was also found to alleviate DSS-induced hepatic injury. Furthermore, the glutathione transferase activity pathway was enriched in the liver of MFGM-treated mice after DSS administration. Mechanistically, prophylactic MFGM enhanced the mucosal barrier by increasing the gene levels of Reg3b and Reg3g. Meanwhile, the alleviation of MFGM on liver injury was dependent on the reduced hepatic oxidative stress.ConclusionsMFGM attenuated colitis and hepatic injury by maintaining the mucosal barrier and bacterial community while inhibiting oxidative stress, which might be an effective therapy of hepatic injury secondary to IBD.

Dataset Information

Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice.

Publications

Milk Fat Globule Membrane Attenuates High-Fat Diet-Induced Obesity by Inhibiting Adipogenesis and Increasing Uncoupling Protein 1 Expression in White Adipose Tissue of Mice.

Similar Datasets

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