Re-Evaluation of Milk-Fat Globule EGF-Factor VIII (MFG-E8) as an Intrinsic Component of the Mouse Milk-Fat Globule Membrane

Nakatani, Hajime; Yasueda, Takehiko; Oshima, Kenzi; Nadano, Daita; Matsuda, Tsukasa

doi:10.1271/bbb.120412

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Therefore, hyperglycemia may partly contribute to the elevated MFG‐E8 levels in T2D. On the other hand, higher levels of insulin and TNF‐α levels in type 2 diabetes might exaggeratedly upregulate MFG‐E8 expression, as evidenced by that in vitro study where insulin and TNF‐α promoted MFG‐E8 production . Further studies, however, are warranted to clarify this point.…”

Section: Discussionmentioning

confidence: 93%

Elevated serum milk fat globule‐epidermal growth factor 8 levels in type 2 diabetic patients are suppressed by overweight or obese status

Ran

Zhang

et al. 2017

IUBMB Life

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Inflammation is the most important link between obesity and type 2 diabetes (T2D). Although milk fat globule-epidermal growth factor 8 (MFG-E8) is a key mediator in anti-inflammatory responses, its role in obesity and diabetes is not yet completely understood. We aimed to measure MFG-E8 serum levels and to explore the role of MFG-E8 in obesity and T2D. Fasting serum MFG-E8 levels were quantified by enzyme-linked immunosorbent assay for 168 individuals, whose oral glucose tolerance test was conducted, and levels of inflammatory factors, including tumor necrosis factor-α (TNF-α) and C-reactive protein, were measured. The participants were subdivided into 66 newly diagnosed T2D individuals, 44 impaired glucose tolerance (IGT) subjects and 58 healthy controls. Their characteristics were further classified as lean or nonlean for investigation. MFG-E8 levels were significantly higher in T2D subjects than in healthy controls (P = 0.028). Decreased levels of MFG-E8 were found in overweight or obese individuals, compared to those in lean subjects, in both the T2D and IGT groups (P < 0.001). Interestingly, MFG-E8 levels showed a negative correlation with body mass index (BMI) and TNF-α levels in the total population and the T2D subgroup. Further, BMI and TNF-α concentrations were found to be independent predictors of MFG-E8 levels in all subjects. MFG-E8 levels are elevated in T2D but suppressed by increased adipose tissues, thereby allowing inflammatory factors to rise to high levels. MFG-E8 may serve as a potential biomarker for obesity and T2D in the clinical setting. © 2017 IUBMB Life, 69(2):63-71, 2017.

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Section: Discussionmentioning

confidence: 93%

Elevated serum milk fat globule‐epidermal growth factor 8 levels in type 2 diabetic patients are suppressed by overweight or obese status

Ran

Zhang

et al. 2017

IUBMB Life

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“…There still remain a number of unanswered questions in our work regarding the interplay between MFGE8, insulin, and insulin signaling under physiological conditions. Insulin has been shown to induce Mfge8 production in vitro ( 35 ). We have previously demonstrated that insulin coordinates inhibition of its own signaling pathway by increasing the amount of MFGE8 at the outer cell membrane where it can bind to the αvβ5 integrin ( 5 ).…”

Section: Resultsmentioning

confidence: 99%

PTP1B mediates the inhibitory effect of MFGE8 on insulin signaling through the β5 integrin

Datta,

Mukherjee,

Podolsky

et al. 2024

Journal of Biological Chemistry

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“…During secretion from cells into milk, LD are progressively enveloped by the apical plasma membrane forming milk fat globules (MFG) with sizes ranging from 0.2-15 μm [2][3][4]. Inside MFG, there is a lipid core surrounded by a complex phospholipid-and protein-coated membrane (MFGM) [5]. The size and features of MFG have received particular interest due to their influence on the manufacturing properties and nutritional quality of dairy products [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Knockout of butyrophilin subfamily 1 member A1 (BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells

Han

Zhang

Xing

et al. 2020

J Animal Sci Biotechnol

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Background: Milk lipids originate from cytoplasmic lipid droplets (LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1A1 (BTN1A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known. Methods: The objective was to knockout BTN1A1 in bovine mammary epithelial cells (BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid (PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Lentivirus-mediated infection of the Cas9/sgRNA expression vector into BMEC resulted in production of a homozygous clone BTN1A1 (−/−). The LD size and content decreased following BTN1A1 gene knockout. The mRNA abundance of fatty acid synthase (FASN) and peroxisome proliferator-activated receptor-gamma (PPARG) was downregulated in the BTN1A1 (−/−) clone. Subcellular analyses indicated that BTN1A1 and LD were co-localized in the cytoplasm. BTN1A1 gene knockout increased the percentage of phosphatidylethanolamine (PE) and decreased phosphatidylcholine (PC), which resulted in a lower PC/PE ratio. Conclusions: Results suggest that BTN1A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.

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Re-Evaluation of Milk-Fat Globule EGF-Factor VIII (MFG-E8) as an Intrinsic Component of the Mouse Milk-Fat Globule Membrane

Cited by 7 publications

References 29 publications

Elevated serum milk fat globule‐epidermal growth factor 8 levels in type 2 diabetic patients are suppressed by overweight or obese status

Elevated serum milk fat globule‐epidermal growth factor 8 levels in type 2 diabetic patients are suppressed by overweight or obese status

PTP1B mediates the inhibitory effect of MFGE8 on insulin signaling through the β5 integrin

Knockout of butyrophilin subfamily 1 member A1 (BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells

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