Polar lipid-enriched milk fat globule membrane supplementation in maternal high-fat diet promotes intestinal barrier function and modulates gut microbiota in male offspring.

Intestinal development plays a critical role in physiology and disease in early life and has long-term effects on the health status throughout the lifespan. Maternal high-fat diet (HFD) fuels the inflammatory reaction and metabolic syndrome, disrupts intestinal barrier function, and alters gut microbiota in offspring. The aim of this study was to evaluate whether polar lipid-enriched milk fat globule membrane (MFGM-PL) supplementation in maternal HFD could promote intestinal barrier function and modulate gut microbiota in male offspring. Obese female rats induced by HFD were supplemented with MFGM-PL during pregnancy and lactation. The offspring were fed HFD for 11 weeks after weaning. MFGM-PL supplementation to dams fed HFD decreased the body weight gain and ameliorated abnormalities of serum insulin, lipids, and inflammatory cytokines in offspring at weaning. Maternal MFGM-PL supplementation promoted the intestinal barrier by increasing the expression of Ki-67, lysozyme, mucin 2, zonula occludens-1, claudin-3, and occludin. Additionally, MFGM-PL supplementation to HFD dams improved gut dysbiosis in offspring. MFGM-PL increased the relative abundance of Akkermansiaceae, Ruminococcaceae, and Blautia. Concomitantly, maternal MFGM-PL treatment increased short-chain fatty acids of colonic contents and G-protein-coupled receptor (GPR) 41 and GPR 43 expressions in the colon of offspring. Importantly, the beneficial effects of maternal MFGM-PL intervention persisted to offspring's adulthood, as evidenced by increased relative abundance of norank_f_Muribaculaceae, Peptostreptococcaceae and Romboutsia and modulated the taxonomic diversity of gut microbiota in adult offspring. In summary, maternal MFGM-PL supplementation improved intestinal development in the offspring of dams fed with HFD, which exerted long-term beneficial effects on offspring intestinal health.

Chitosan oligosaccharide attenuates hepatic steatosis in HepG2 cells via the activation of AMP-activated protein kinase.

Chitosan oligosaccharides (COSs), oligomers of decomposed chitosan possess many biological functions including immunomodulatory, antitumor, and antiinflammation. The aim of this study was to investigate the protective effects of COS against free fatty acid (FFA)-induced cellular hepatic steatosis and underlying mechanisms in HepG2 cells. Results showed that COS significantly reduced the lipid contents and elevated the activities of antioxidant enzymes including total-superoxide dismutase, glutathione peroxidase, and catalase in FFA-stimulated HepG2 cells. COS phosphorylated the acetyl-CoA carboxylase and reduced both mRNA and protein levels of lipogenesis markers including fatty acid synthase and sterol regulatory element-binding protein 1c. COS also significantly increased the expression levels of fatty acid oxidation-related factors including carnitine palmitoyltransferase 1A, acyl-coenzyme A oxidase 1, and peroxisome proliferators-activated receptor α. Besides, COS markedly phosphorylated AMP-activated protein kinase (AMPK). The inhibition of lipogenesis and the enhancement of fatty acid oxidation induced by COS were all blocked by AMPK antagonist (compound C), showing that the attenuation of hepatic steatosis by COS was dependent on AMPK activation. In conclusion, COS attenuated hepatic steatosis via suppressing lipid synthesis and enhancing fatty acid oxidation. AMPK was also involved in the alleviation of hepatic steatosis by COS. These results indicated that COS might be used as a potential ingredient to ameliorate nonalcoholic fatty liver disease. PRACTICAL APPLICATIONS: Nonalcoholic fatty liver disease (NAFLD) has been regarded as pathological fat deposition in the liver, which includes a range of pathologies, from steatosis to steatohepatitis, fibrosis, and cellular carcinoma. Our findings demonstrated that Chitosan oligosaccharides (COS) attenuated steatosis via improving lipid metabolism. COS suppressed lipogenesis and also enhanced fatty acid oxidation. Besides, the underlying molecular mechanism whereby COS elicited these beneficial effects has also been proved to be through the modulation of upstream protein kinase, AMP-activated protein kinase. This study provides new knowledge to support that COS might be used as a food supplement for the prevention of NAFLD.

Yogurt Enriched with Inulin Ameliorated Reproductive Functions and Regulated Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice.

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota-bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w/w) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia. PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.

Milk Polar Lipids Supplementation to Obese Rats During Pregnancy and Lactation Benefited Skeletal Outcomes of Male Offspring.

SCOPE: Dietary intervention to obese dams during pregnancy and lactation period provides avenues for improving metabolic profiles of the offspring. In the current study, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to obese dams during pregnancy and lactation on the skeletal outcomes of male offspring are investigated. METHODS AND RESULTS: MFGM-PL is supplemented to obese rats induced by high-fat diet during pregnancy and lactation at a dose of 400 mg kg-1 body weight. Results show that maternal MFGM-PL supplementation significantly ameliorates the stunted skeletal growth of male offspring at weaning. In adulthood offspring, maternal MFGM-PL supplementation protects against high-fat diet (HFD)-induced bone microstructure degeneration and bone marrow adipocyte accumulation. Further investigation shows that maternal supplementation of MFGM-PL significantly ameliorates insulin resistance and increases the mRNA expression of growth hormone releasing hormone (GHRH) in the hypothalamus of HFD offspring. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is subsequently enhanced in MFGM-PL + HFD offspring, contributing to the beneficial skeletal outcomes. CONCLUSION: The findings suggest that maternal MFGM-PL supplementation of HFD dam during pregnancy and lactation shows desirable effects on fetal skeletal development, with lasting beneficial programming impacts on skeletal outcomes of offspring.

Supplementation of milk polar lipids to obese dams improves neurodevelopment and cognitive function in male offspring.

Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.

Water Extract of Potentilla discolor Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

Potentilla discolor Bunge, as a traditional Chinese medicine, exhibits many phytochemical activities. The aim of the present study was to investigate the effects of Potentilla discolor Bunge water extract (PDBW) and its underlying mechanisms on gluconeogenesis and glycogen synthesis in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice. LC-MS/MS analyses of PDBW identified 6 major compounds including apigenin-7-O-ß-D-glucoside, epicatechin, quercetin 3-O-ß-D-glucuronide, kaempferol-3-O-ß-D-glucopyranoside, scutellarin, and quercitrin. In the study, a mouse model of type 2 diabetes was induced by 4-week HFD combined with STZ (40 mg/kg body weight) for 5 days. After oral administration of PDBW at 400 mg/kg body weight daily for 8 weeks, the mice with type 2 diabetes showed significant decrease in the levels of fasting blood glucose and glycated hemoglobin A1c (HbA1c), and increase in the insulin level. PDBW improved the glucose tolerance, insulin sensitivity and lipid profiles. Furthermore, PDBW inhibited the mRNA levels of key gluconeogenic enzymes [phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)] in liver. PDBW also promoted glycogen synthesis by raising the liver glycogen content, decreasing the phosphorylation of glycogen synthase (GS) and increasing the phosphorylation of glycogen synthase kinase3ß (GSK3ß). Besides, PDBW induced the activation of protein kinase B (Akt) and AMP-activated protein kinase (AMPK), which might explain changes in the phosphorylation of above enzymes. In summary, PDBW supplementation ameliorates metabolic disorders in a HFD/STZ diabetic mouse model, suggesting the potential application of PDBW in prevention and amelioration of type 2 diabetes.

Dietary Milk Fat Globule Membrane Restores Decreased Intestinal Mucosal Barrier Development and Alterations of Intestinal Flora in Infant-Formula-Fed Rat Pups.

SCOPE: Milk fat globule membrane (MFGM), which contains abundant polar lipids and glycoproteins, can narrow the gap in growth and development between breast-fed and infant-formula-fed babies. The objective of this study is to evaluate the effect of MFGM supplementation in infant formula on intestinal epithelium maturation, tight junctions, and gut colonization in rat pups. METHODS AND RESULTS: Sprague Dawley rat pups consume one of the five diets from postnatal day 8, including rat breastfeeding (BF), infant formula (IF), and infant formula containing MFGM at 260 mg kg-1 body weight (BW), 520 mg kg-1 BW, or 1040 mg kg-1 BW. Results show that MFGM supplementation in infant formula can facilitate intestinal mucosal barrier maturation via promoting intestinal proliferation and differentiation, and increasing tight junction proteins. In addition, compared with that of the IF pups, the intestinal flora composition of MFGM-supplemented pups is more similar to that of BF pups. CONCLUSION: MFGM supplementation in infant formula can restore the intestinal development in infant-formula-fed pups, which suggests that the supplementation of MFGM in infant formula can better mimic breast milk.

Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota.

This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.

Flavor formation in frying process of green onion (Allium fistulosum L.) deep-fried oil.

Fried allium oil has been widely used in traditional Chinese home cooking and recently has grown in popularity in the food manufacturing industry. Thus, physical and chemical changes during frying process were measured to investigate the flavor formation mechanism in green onion (Allium fistulosum L.) deep-fried oil. With the increase of the oil temperature, important variations took place when the temperature rose above 140 °C during the whole frying process. A detailed study of these changes was made from both macro and micro aspects. From a macro perspective, sensory attributes including burnt, fried, oily, cooked vegetable and salty were strengthened. Meanwhile, the reference points of the oil samples on the fingerprint chart were distinguishable from others by electronic nose. In addition, contents of furans and furanones, sulfur-containing compounds, aldehydes and alcohols increased sharply according to SAFE-GC-MS analysis from a microscopic point of view, and contents of unsaturated fatty acids dropped remarkably while the saturated ones increased. These changes were considered to be caused by interactions between carbohydrates, proteins and fats in the deep-fried system and thermo degradations of sugars, amino acids and fats. The results indicated that the stage, when frying at temperatures ranging from 140 °C to 165 °C, was the most significant period for the flavor formation of the deep-fried oil.

Beneficial Effects of Potentilla discolor Bunge Water Extract on Inflammatory Cytokines Release and Gut Microbiota in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

Potentilla discolor Bunge (PDB), a perennial herb, has been used as a traditional Chinese medicine in the therapy of many diseases. The aim of the current study was to investigate the effect of PDB water extract on systemic inflammation and gut microbiota in type 2 diabetic (T2D) mice induced by high-fat diet (HFD) and streptozotocin (STZ) injection. C57BL/6J mice were randomly divided into a normal diet (ND) group, T2D group, and PDB group (diabetic mice treated with PDB water extract at a dose of 400 mg/kg body weight). Results showed that PDB significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines in serum. Further investigation showed that PDB significantly reduced the ratio of Firmicutes/Bacteroidetes and the relative abundance of Proteobacteria in fecal samples of diabetic mice. In addition, PDB notably alleviated intestinal inflammation as evidenced by decreased expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB), and inflammatory cytokines. PDB also reversed the decreased expression of intestinal mucosal tight junction proteins including Claudin3, ZO-1, and Occludin. Meanwhile, the levels of fecal acetic acid and butyric acid and their specific receptors including G-protein-coupled receptor (GPR) 41 and 43 expression in the colon were also increased after PDB treatment. Our results indicated that PDB might serve as a potential functional ingredient against diabetes and related inflammation.

Anti-anaemia efficacy of ß-lactoglobulin hydrolysate-iron complex on iron-deficient anaemic rats.

PURPOSE: The effects of orally administered ß-lactoglobulin hydrolysate-iron complex (ß-LGH-Fe) on haematological and biochemical parameters in anaemic rats were evaluated. Female weaning Sprague-Dawley rats were fed with iron-deficient diet to induce iron deficiency anaemia. After 6 weeks, the obtained anaemic rats were divided into five groups: iron deficiency control group (iron-deficient diet without ß-LGH-Fe complex supplementation, IDC); three groups supplemented with different dosages of ß-LGH-Fe complex (0.5 mg Fe/kg BW, iron-deficient diet with low ß-LGH-Fe, IDLFe; 2.0 mg Fe/kg BW, iron-deficient diet with medium ß-LGH-Fe, IDMF; 4.0 mg Fe/kg BW, iron-deficient diet with high ß-LGH-Fe, IDHFe); and ferrous sulphate-supplemented group at a dosage of 2.0 mg Fe/kg BW. RESULTS: ß-LGH-Fe complex could significantly improve hematocrit and haemoglobin decrease, and normalise the serum iron level, total iron-binding capacity and transferrin saturation of anaemic rats in a dose-dependent manner. Serum ferritin content and hepatic nonheme iron level were also increased. In addition, the antioxidant enzyme activities of superoxidase dismutase, catalase and glutathione peroxidase in both plasma and liver homogenate were improved. The production of malondialdehyde and pro-inflammatory cytokines (TNF-α and IL-6) decreased. CONCLUSIONS: It suggests that ß-LGH-Fe complex can ameliorate iron deficiency anaemia, which might make it a potential ingredient with anti-anaemia activity.