Dietary Milk Fat Globule Membrane Research Articles

180 Dietary milk fat globule membrane alters intestinal microbiota of neonatal piglet following lipopolysaccharide challenge and marker of neuroinflammation

Abstract Early life stress exposure can increase morbidity and reduce animal wellbeing throughout life. Dysregulated gut function has been associated with neurological changes, and neurological changes affect gut homeostasis. Maternal milk is the gold-standard for yielding developmental benefits to offspring. Identification of milk components has led to an understanding of the bioactive nutrients important in neonatal development. Components of the milk fat globule membrane (MFGM) contribute immensely to neonatal gut health and neurodevelopment. However, mechanisms of actions are still being defined. The objective is to understand how dietary MFGM modulates the gut microbiota, blood-brain barrier tight junctions, and brain inflammatory markers following lipopolysaccharide (LPS) challenge. Piglets (n = 24, one-d-old) were assigned to soy (CON) or MFGM phospholipid supplemented diet (0.75% wt/wt) ± LPS (100 µg/kg body weight) in a 2 × 2 factorial design (n = 6 animals•diet-1•challenge-1.). Piglets were fed for 21 d and 6 animals/diet received saline or LPS injections 4 h before euthanasia. Colonic microbiota was characterized through 16s rRNA gene sequencing, while hypothalamus samples were collected to evaluate brain barrier function and inflammation-related genes using RT-qPCR. Microbiota data were processed using QIIME2 with DADA2 plugin and analyzed for alpha-diversity, beta-diversity, and differential abundance in R software. Gene transcription data were analyzed by a 2 × 2 experimental factorial design using the PROC MIXED procedure of SAS. Principal coordinates analysis indicated that MFGM-fed groups exhibited an observable separation from CON-fed groups in terms of microbial community structures (P < 0.05). Firmicutes_A, Bacteroidota, and Firmicutes_D were the predominant phyla across all treatments, with average proportions to be 52.21 %, 24.36 %, and 18.46 %, respectively. At genus level, MFGM + Saline group down-regulated Corynebacterium by 88.00 % (q < 0.05) and Unclassified Muribaculaceae by 73.33 % (0.050.05). However, there was an MFGM × LPS interaction (P < 0.05) observed for nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha, in which MFGM attenuated the LPS-induced increase in mRNA relative abundance (3.62 and 2.39 ± 0.38). In conclusion, dietary MFGM altered neonatal piglet intestinal microbiota and an important signaling molecule of the neuroinflammatory response following LPS challenge.

PSVI-13 Dietary Milk Fat Globule Membrane Improves Neonatal Piglet Intestinal Architecture and Enhances Mucosal Diamine Oxidase Activity Following Lipopolysaccharide Challenge

Abstract Early life stressors alter the trajectory of gut development and impair nutrient utilization, barrier function, and animal performance throughout life. Gastrointestinal (GI) maladies increase morbidity and mortality in neonates, and dietary nutrients are essential in supporting GI function. Although maternal milk is the gold-standard for yielding developmental benefits to offspring, genetic selection in the modern sow has resulted in large litter size and milk yield potentially insufficient to achieve the high biological growth potential in sow-reared piglets. Research into milk quality has led to the identification of many bioactive nutrients important in neonatal development. Components of the milk fat globule membrane (MFGM) contribute immensely to neonatal nutrition and gut health. However, mechanisms of actions are still being defined. The objective is to define the effect of MFGM supplementation on neonatal piglet intestinal health. We hypothesize dietary MFGM will enhance piglet intestinal architecture and tight junction (TJ) protein abundance, attenuating systemic lipopolysaccharide (LPS)-induced intestinal barrier disruption. One-day-old piglets (n = 32) were assigned to soy (CON) or MFGM phospholipid supplemented diet (0.75% wt/wt) ± LPS (100 µg/kg body weight) challenge in a 2 × 2 factorial design (n = 8/diet/challenge). Piglets were fed for 21 d and 8 animals/diet received saline or LPS injections 4 h before euthanasia. Piglet weights and feed intake were recorded daily to calculate performance. Intestinal tissues were collected to assess villus height (VH) and crypt depth (CD) by hematoxylin and eosin staining. Two biomarkers of intestinal integrity, intestinal fatty acid-binding protein (I-FABP) and diamine oxidase (DAO), were measured in serum or tissue. Protein abundance of claudin-1 and occludin in ileal and colonic mucosa were detected by Western blot. Data were analyzed by 2 × 2 factorial arrangement of traetments using the PROC MIXED. Dietary MFGM had no adverse impact on growth performance or TJ proteins (P > 0.05). Dietary MFGM increased VH (CON: 348.8 and MFGM: 427.0 ± 26.79 µm) and decreased CD (CON: 166.3 and MFGM: 147.4 ± 8.42 µm) in ileum, thereby increasing the VH: CD ratio (CON: 2.2; MFGM: 3.1 ± 0.13; P < 0.05). Further, LPS treatment increased serum I-FABP by 4.4-fold and decreased jejunal mucosal DAO by 0.5-fold compared with saline treatment (P < 0.05). Additionally, there was a 93.1 % increase in colon DAO activity with MFGM diet compared with soy-fed pigs, regardless of LPS challenge (P < 0.05). Dietary MFGM improved neonatal piglet ileum architecture and increased colon DAO activity, potentially attenuating the intestinal barrier disruption following LPS challenge.

Impacts of Formula Supplemented with Milk Fat Globule Membrane on the Neurolipidome of Brain Regions of Piglets.

The milk fat globule membrane (MFGM) appears to play an important role in infant neurocognitive development; however, its mechanism(s) of action remains unclear. This study aimed to investigate the role of a dietary MFGM supplement on the lipid profiles of different neonatal brain regions. Ten-day-old male piglets (4–5 kg) were fed unsupplemented infant formula (control, n = 7) or an infant formula supplemented with low (4%) or high (8%) levels of MFGM (n = 8 each) daily for 21 days. Piglets were then euthanized, and brain tissues were sectioned. Untargeted liquid chromatography-mass spectrometry lipidomics was performed on the cerebellum, hippocampus, prefrontal cortex, and the rest of the brain. The analyses identified 271 and 171 lipids using positive and negative ionization modes, respectively, spanning 16 different lipid classes. MFGM consumption did not significantly alter the lipidome in most brain regions, regardless of dose, compared to the control infant formula. However, 16 triacylglyceride species were increased in the hippocampus (t-test, p-value < 0.05) of the high-supplemented piglets. Most lipids (262 (96.7%) and 160 (93.6%), respectively) differed significantly between different brain regions (ANOVA, false discovery rate corrected p-value < 0.05) independent of diet. Thus, this study highlighted that dietary MFGM altered lipid abundance in the hippocampus and detected large differences in lipid profiles between neonatal piglet brain regions.

Effects of Post-natal Dietary Milk Fat Globule Membrane Polar Lipid Supplementation on Motor Skills, Anxiety, and Long-Term Memory in Adulthood.

Early life nutrition critically impacts post-natal brain maturation and cognitive development. Post-natal dietary deficits in specific nutrients, such as lipids, minerals or vitamins are associated with brain maturation and cognitive impairments. Specifically, polar lipids (PL), such as sphingolipids and phospholipids, are important cellular membrane building blocks and are critical for brain connectivity due to their role in neurite outgrowth, synaptic formation, and myelination. In this preclinical study, we assessed the effects of a chronic supplementation with a source of PL extracted from an alpha-lactalbumin enriched whey protein containing 10% lipids from early life (post-natal day (PND) 7) to adulthood (PND 72) on adult motor skills, anxiety, and long-term memory. The motor skills were assessed using open field and rotarod test. Anxiety was assessed using elevated plus maze (EPM). Long-term object and spatial memory were assessed using novel object recognition (NOR) and Morris water maze (MWM). Our results suggest that chronic PL supplementation improved measures of spatial long-term memory accuracy and cognitive flexibility in the MWM in adulthood, with no change in general mobility, anxiety and exploratory behavior. Our results indicate memory specific functional benefits of long-term dietary PL during post-natal brain development.

Milk fat globule membrane attenuates high fat diet-induced neuropathological changes in obese Ldlr-/-.Leiden mice.

Milk-fat globule membrane (MFGM) is a complex structure secreted by the mammary gland and present in mammalian milk. MFGM contains lipids and glycoproteins as well as gangliosides, which may be involved in myelination processes. Notably, myelination and thereby white matter integrity are often altered in obesity. Furthermore, MFGM interventions showed beneficial effects in obesity by affecting inflammatory processes and the microbiome. In this study, we investigated the impact of a dietary MFGM intervention on fat storage, neuroinflammatory processes and myelination in a rodent model of high fat diet (HFD)-induced obesity. 12-week-old male low density lipoprotein receptor-deficient Leiden mice were exposed to a HFD, a HFD enriched with 3% whey protein lipid concentrate (WPC) high in MFGM components, or a low fat diet. The impact of MFGM supplementation during 24-weeks of HFD-feeding was examined over time by analyzing body weight and fat storage, assessing cognitive tasks and MRI scanning, analyzing myelinization with polarized light imaging and examining neuroinflammation using immunohistochemistry. We found in this study that 24 weeks of HFD-feeding induced excessive fat storage, increased systolic blood pressure, altered white matter integrity, decreased functional connectivity, induced neuroinflammation and impaired spatial memory. Notably, supplementation with 3% WPC high in MFGM components restored HFD-induced neuroinflammation and attenuated the reduction in hippocampal-dependent spatial memory and hippocampal functional connectivity. We showed that supplementation with WPC high in MFGM components beneficially contributed to hippocampal-dependent spatial memory, functional connectivity in the hippocampus and anti-inflammatory processes in HFD-induced obesity in rodents. Current knowledge regarding exact biological mechanisms underlying these effects should be addressed in future studies.

The Impact of Milk Fat Globule Membrane with Exercise on Age-Related Degeneration of Neuromuscular Junctions.

Morphological changes in neuromuscular junctions (NMJs), which are synapses formed between α-motor neurons and skeletal muscle fibers, are considered to be important in age-related motor dysfunction. We have previously shown that the intake of dietary milk fat globule membrane (MFGM) combined with exercise attenuates age-related NMJ alterations in the early phase of aging. However, it is unclear whether the effect of MFGM with exercise on age-related NMJ alterations persists into old age, and whether intervention from old age is still effective when age-related changes in NMJs have already occurred. In this study, 6- or 18-month-old mice were treated with a 1% MFGM diet and daily running wheel exercise until 23 or 24 months of age, respectively. MFGM treatment with exercise was effective in suppressing the progression of age-related NMJ alterations in old age, and even after age-related changes in NMJs had already occurred. Moreover, the effect of MFGM intake with exercise was not restricted to NMJs but extended to the structure and function of peripheral nerves. This study demonstrates that MFGM intake with exercise may be a novel approach for improving motor function in the elderly by suppressing age-related NMJ alterations.

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

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. 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 260mg kg-1 body weight (BW), 520mg kg-1 BW, or 1040mg 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. 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.

Dietary milk fat globule membrane supplementation during late gestation increased the growth of neonatal piglets by improving their plasma parameters, intestinal barriers, and fecal microbiota.

Milk fat globule membrane (MFGM), mainly comprising protein and fat, has been reported to have multiple biological functions for relieving intestinal inflammation and enhancing growth performance. We hypothesized that MFGM supplementation into sows' diet during late gestation can have a positive impact on the intestinal microecology of sows and their piglets, as well as on the growth of neonates. Therefore, the present study was conducted to investigate such effects and their potential mechanisms. Twenty-two pregnant sows were selected and randomly divided into the CON group (basal diet) and MFGM group (basal diet supplemented with 9.9 g per day MFGM). The feeding period began from d 85 of gestation and until farrowing. The concentrations of albumin (ALB), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA) in plasma and short-chain fatty acids (SCFAs) in feces of sows from the MFGM group were determined. The concentrations of growth hormone (GH), immunoglobulin A (IgA), glucose (GLU), and NEFA in the umbilical cord blood in the MFGM group were significantly higher than those in the CON group. Piglets from the MFGM group showed improved growth performance, increased villus height in the jejunum, decreased crypt depth in the duodenum and jejunum, upregulated mRNA expressions of tight junctions (namely, Occludin; Claudin-1, Claudin-2, and Claudin-4; zonulin-1 (ZO-1)); mucins such as Mucin 2, Mucin 4, Mucin 13, and Mucin 20; and immune-related genes, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-22 (IL-22), toll-like receptor 2 (TLR2), and toll-like receptor 4 (TLR4). In addition, the abundance of Prevotella in the feces of sows at farrowing and the abundance of Christensenellaceae_R-7_group in the feces of 21 day-old piglets from the MFGM group were significantly higher. Further correlation analysis revealed that the Christensenellaceae_R-7_group was positively correlated with the relative mRNA expressions of Occludin, Claudin-1, Claudin-2, Claudin-4, Mucin 13, TLR2, and TLR4. In conclusion, MFGM supplementation during late gestation improved the physiological status of sows by improving their plasma parameters and intestinal microecology. The improved provision of nutrients through the umbilical cord blood and optimized microbiota colonization in neonatal piglets were beneficial to the intestinal morphological structure and barrier functions, consequently improving the growth performance of neonates during lactation. These findings provide insights into the future applications of MFGM with regard to maternal–fetal nutrition and a new option for nutritional intervention of neonates through maternal dietary manipulation.

Continuous Supplementation of Milk Fat Globule Membrane with Habitual Exercise from a Young Age Improves Motor Coordination and Skeletal Muscle Function in Aged Mice.

Since the decline of physical performance gradually progresses with aging, continuous exercise with nutritional supplementation from a young age is a feasible and effective way to maintain a comfortable life until late old age. We examined the effects of continuous milk fat globule membrane (MFGM) supplementation combined with voluntary running exercise (VR) for prevention of aging-associated declines in physical performance in naturally aging mice. The MFGM with VR group showed a significantly attenuated age-related decline in motor coordination and suppression of the loss of muscle mass and strength. Compared with the control group, the MFGM with VR group showed significantly higher mRNA and protein expression for docking protein 7, which maintains neuromuscular junction (NMJ) integrity, in the quadriceps muscles. These results suggest that dietary MFGM and VR attenuate natural aging-related decline in motor coordination and muscle function by regulating NMJ integrity.

Dietary milk fat globule membrane regulates JNK and PI3K/Akt pathway and ameliorates type 2 diabetes in mice induced by a high-fat diet and streptozotocin

Milk fat globule membrane (MFGM) was found to possess anti-cancer, anti-obesity and anti-inflammatory activities. The present study was carried out to evaluate the effects and possible underlying mechanisms of MFGM on type 2 diabetes (T2D) in mice. Results showed that 8-week MFGM supplementation had beneficial effects in ameliorating hyperglycemia and dyslipidemia in T2D mice induced with a high-fat diet and streptozotocin. MFGM also protected the liver and pancreas histological structures in T2D mice. Additionally, MFGM enhanced glycogen synthesis, which was associated with inhibition of glycogen synthase kinase 3 beta and activation of glycogen synthase. Furthermore, a mechanistic study illuminated that MFGM likely ameliorated glucose metabolism disorder by promoting the phosphatidylinositol 3-kinase/protein kinase B pathway while suppressing c-Jun N-terminal kinase signaling in liver and skeletal muscle. These findings suggest that MFGM may be useful as a potential functional food ingredient against diabetes.

Light rhythmic exercise with dietary milk fat globule membrane improves physical fitness in an elderly Japanese population: a double-blind randomized placebo-controlled trial.

This study aimed to investigate the efficacy of home-based, light gymnastic exercise plus dietary milk fat globule membrane (MFGM) intake on physical fitness of an elderly Japanese sample in a pilot, double-blind, randomized, placebo-controlled trial. Seventy-one subjects (male, n=13; female, n=58) were randomly assigned into two groups: placebo (n=35 [male, n=6; female, n=29]) and MFGM group (n=36 [male, n=7; female, n=29]). The intervention was eight weeks. Subjects ingested either MFGM (1g/day) or placebo tablets daily and engaged in an exercise program daily. Physical function tests were performed at baseline and after four and eight weeks. Foot tapping and open-close stepping scores significantly increased from baseline to eight weeks in the MFGM group. Study results suggest daily MFGM ingestion might further enhance the effects of light-intensity exercise in healthy elderly people.

Effects of dietary supplementation with milk fat globule membrane on the physical performance of community-dwelling Japanese adults: a randomised, double-blind, placebo-controlled trial.

We conducted a randomised, double-blind, placebo-controlled trial to elucidate the effects of dietary milk fat globule membrane (MFGM) on the physical performance of community-dwelling Japanese adults. For this 24-week study, 115 middle-aged subjects (range 50-70 years old) were invited, of whom 113 (seventy-two women, forty-one men) completed the trial. Participants were then divided into either the placebo control or MFGM group. Measurements of physical performance (without undertaking any mandatory exercise) examining muscle strength, agility and balance were tested every 6 weeks until 24 weeks. Analyses were performed using the intention-to-treat method for all participants. Although the effects of MFGM on muscle strength and agility were not significant, we noted that the parameter for balance (such as the ability to stand on one leg with eyes closed for longer durations) increased in the MFGM group (mean 10·1 (95 % CI 8·25, 12·4) s) compared with the placebo (mean 7·53 (95 % CI 6·11, 9·30) s) (P = 0·046). Similarly, application of the mixed-effect model for repeated measures under unstructured covariance also revealed that the effect of MFGM was significant when compared with the placebo (10·2 (95 % CI 8·33, 12·4) v. 7·61 (95 % CI 6·17, 9·30) s) (P = 0·045). In conclusion, we demonstrated that MFGM had an effect on the physical performance of community-dwelling Japanese adults despite mandatory exercise. However, studies using larger cohorts of individuals from different demographic backgrounds are required to further elucidate the mechanisms underlying these effects and to extend the application of MFGM.

Dietary supplementation with bovine-derived milk fat globule membrane lipids promotes neuromuscular development in growing rats

BackgroundThe milk fat globule membrane (MFGM) is primarily composed of polar phospho- and sphingolipids, which have established biological effects on neuroplasticity. The present study aimed to investigate the effect of dietary MFGM supplementation on the neuromuscular system during post-natal development.MethodsGrowing rats received dietary supplementation with bovine-derived MFGM mixtures consisting of complex milk lipids (CML), beta serum concentrate (BSC) or a complex milk lipid concentrate (CMLc) (which lacks MFGM proteins) from post-natal day 10 to day 70.ResultsSupplementation with MFGM mixtures enriched in polar lipids (BSC and CMLc, but not CML) increased the plasma phosphatidylcholine (PC) concentration, with no effect on plasma phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylserine (PS) or sphingomyelin (SM). In contrast, muscle PC was reduced in rats receiving supplementation with both BSC and CMLc, whereas muscle PI, PE, PS and SM remained unchanged. Rats receiving BSC and CMLc (but not CML) displayed a slow-to-fast muscle fibre type profile shift (MyHCI → MyHCIIa) that was associated with elevated expression of genes involved in myogenic differentiation (myogenic regulatory factors) and relatively fast fibre type specialisation (Myh2 and Nfatc4). Expression of neuromuscular development genes, including nerve cell markers, components of the synaptogenic agrin–LRP4 pathway and acetylcholine receptor subunits, was also increased in muscle of rats supplemented with BSC and CMLc (but not CML).ConclusionsThese findings demonstrate that dietary supplementation with bovine-derived MFGM mixtures enriched in polar lipids can promote neuromuscular development during post-natal growth in rats, leading to shifts in adult muscle phenotype.

DIETARY MILK FAT GLOBULE MEMBRANE WITH SEMIWEEKLY LIGHT EXERCISE IMPROVES CHOICE STEPPING REACTION TIME IN HEALTHY JAPANESE ELDERLY SUBJECTS: A RANDOMIZED DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL

This study aimed to demonstrate the beneficial effects of nutritional supplementation with milk fat globule membrane combined with light exercise on agility, which predicts falls in the elderly. Twenty-five healthy volunteers (aged 60-74 years old; male/female = 11/14) were enrolled in a randomized, double-blind, placebo-controlled intervention study. The subjects ingested placebo or milk fat globule membrane (1 g/day) tablets daily for 5 weeks and engaged in a 30-min light exercise program semiweekly. After 5 weeks, agility was evaluated using the choice stepping reaction time. The milk fat globule membrane group had significantly shorter motion start and reaction times compared to the placebo group. The reduction in motion start and reaction times was significantly greater in the milk fat globule membrane compared to the placebo group. In conclusion, this study provides evidence that dietary milk fat globule membrane supplementation improves choice stepping reaction time and agility in the healthy elderly population.

Effects of Nutritional Supplementation with Milk Fat Globule Membrane on Physical and Muscle Function in Healthy Adults Aged 60 and Over with Semiweekly Light Exercise: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.

This study aimed to demonstrate the beneficial effects of nutritional supplementation with dietary milk fat globule membrane (MFGM) on physical performance and skeletal muscle function in healthy adults aged 60 and over with semiweekly light exercise. The study was designed as a randomized double-blind controlled trial. Twenty-two Japanese participants (10 men, 12 women) aged 60-73 y were assigned to one of two groups (11 [5 men, 6 women] in each). One group received MFGM tablets (1 g MFGM/d), and the other received placebo tablets daily for 10 wk. Both groups participated in a twice-weekly light exercise program. Physical function tests and surface electromyography (EMG) were conducted at the baseline and after 5 and 10 wk. Chair stand time significantly shortened in both groups after 10 wk compared with that at the baseline. The average time shortened more considerably in the MFGM group than in the placebo group, although the change was not statistically significant. Both knee extension strength and the cross-sectional area of the quadriceps muscles significantly increased from baseline in the MFGM group but not in the placebo group. Surface EMG showed that muscle fiber conduction velocity increased significantly after 10 wk from the baseline only in the MFGM group. The increase from the baseline was significantly greater in the MFGM group than in the placebo group. Daily supplementation with MFGM increased motor unit action potential conduction and improved muscle strength and physical performance in healthy Japanese adults aged 60 y and over paired with semiweekly light exercise.

Dietary milk fat globule membrane supplementation combined with regular exercise improves skeletal muscle strength in healthy adults: a randomized double-blind, placebo-controlled, crossover trial.

BackgroundOur previous studies demonstrated that dietary supplementation with milk fat globule membrane (MFGM) combined with habitual exercise improved muscle strength by stimulating neuromuscular development in mice. This study aimed to demonstrate the beneficial effects of dietary MFGM supplementation plus regular exercise on muscle strength and neuromuscular function in healthy humans.MethodsThe study was designed as a randomized, double-blind, placebo-controlled, crossover trial. Fourteen Japanese adults aged 31–48 years took daily MFGM (1 g) or placebo tablets during the 4-week study period and attended a training program twice a week. Physical function tests and surface electromyography (EMG) were conducted at baseline and at the end of the study period.ResultsThe MFGM group had significantly greater leg extension strength than the placebo group after the 4-week study period. Surface EMG showed that the MFGM group had a significantly higher root mean square amplitude than the placebo group, which indicated that the MFGM group had higher motor unit activity.ConclusionsDietary MFGM supplementation combined with regular exercise improves skeletal muscle strength, which may be due to increased motor unit recruitment in healthy Japanese middle-aged adults.

Daily consumption of milk fat globule membrane plus habitual exercise improves physical performance in healthy middle-aged adults.

Our recent studies demonstrated that habitual exercise plus dietary supplementation with milk fat globule membrane (MFGM) improved endurance capacity and muscle function by stimulating neuromuscular development in mice. The aim of this study was to investigate the efficacy of dietary MFGM supplementation plus habitual exercise on the physical performance of middle-aged Japanese adults in a pilot randomized, double-blind, placebo-controlled trial. Forty-four subjects (men, n = 22; women, n = 22) were randomly assigned into two groups: one received placebo tablets (placebo group, n = 22 [men, n = 11; women, n = 11]), while the other received MFGM tablets (MFGM group, n = 22 [men, n = 11; women, n = 11]). The subjects ingested either MFGM (1 g/day) or placebo (1 g/day of whole milk powder) tablets every day for the 10-week study period and engaged in an exercise training program twice per week. A physical function test was performed at baseline and at 5 and 10 weeks. A significant group-by-time interaction was found for the side step test, muscle cross-sectional area (CSA), and muscle fiber conduction velocity (MFCV). In the placebo group, there were no significant intragroup differences. In the MFGM group, side step score and muscle CSA were significantly greater at 10 weeks compared to the baseline, and MFCV was significantly higher than that in the placebo group at 10 weeks. The changes in percentage of the side step score, muscle CSA, and MFCV in the MFGM group were significantly higher than in the placebo group at 10 weeks. These results suggest that daily MFGM ingestion combined with regular exercise might enhance physical performance such as agility in middle-aged adults.

Dietary milk fat globule membrane improves endurance capacity in mice.

Milk fat globule membrane (MFGM) comprises carbohydrates, membrane-specific proteins, glycoproteins, phospholipids, and sphingolipids. We evaluated the effects of MFGM consumption over a 12-wk period on endurance capacity and energy metabolism in BALB/c mice. Long-term MFGM intake combined with regular exercise improved endurance capacity, as evidenced by swimming time until fatigue, in a dose-dependent manner. The effect of dietary MFGM plus exercise was accompanied by higher oxygen consumption and lower respiratory quotient, as determined by indirect calorimetry. MFGM intake combined with exercise increased plasma levels of free fatty acids after swimming. After chronic intake of MFGM combined with exercise, the triglyceride content in the gastrocnemius muscle increased significantly. Mice given MFGM combined with exercise had higher mRNA levels of peroxisome proliferator-activated receptor-γ coactivator 1α (Pgc1α) and CPT-1b in the soleus muscle at rest, suggesting that increased lipid metabolism in skeletal muscle contributes, in part, to improved endurance capacity. MFGM treatment with cyclic equibiaxial stretch consisting of 10% elongation at 0.5 Hz with 1 h on and 5 h off increased the Pgc1α mRNA expression of differentiating C2C12 myoblasts in a dose-dependent manner. Supplementation with sphingomyelin increased endurance capacity in mice and Pgc1α mRNA expression in the soleus muscle in vivo and in differentiating myoblasts in vitro. These results indicate that dietary MFGM combined with exercise improves endurance performance via increased lipid metabolism and that sphingomyelin may be one of the components responsible for the beneficial effects of dietary MFGM.

Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence-accelerated mice

We examined the effects of habitual exercise plus nutritional intervention through consumption of milk fat globule membrane (MFGM), a milk component, on aging-related deficits in muscle mass and function in senescence-accelerated P1 mice. Combining wheel-running and MFGM (MFGMEx) intake significantly attenuated age-related declines in quadriceps muscle mass (control: 318 ± 6 mg; MFGMEx: 356 ± 9 mg; P < 0.05) and in contractile force (1.4-fold and 1.5-fold higher in the soleus and extensor digitorum longus muscles, respectively). Microarray analysis of genes in the quadriceps muscle revealed that MFGMEx stimulated neuromuscular development; this was supported by significantly increased docking protein-7 (Dok-7) and myogenin mRNA expression. Treatment of differentiating myoblasts with MFGM-derived phospholipid or sphingolipid fractions plus mechanical stretching also significantly increased Dok-7 mRNA expression. These findings suggest that habitual exercise plus dietary MFGM improves muscle function deficits through neuromuscular development, and that phospholipid and sphingolipid in MFGM contribute to its physiological actions.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-339) contains supplementary material, which is available to authorized users.

乳脂肪球膜の摂取によるHos:HR-1（HR-1）マウスとヒトにおけるTEWL改善効果ならびにマウスでの遺伝子発現解析

バター製造で発生するバターミルクには，乳脂肪球膜（Milk Fat Globule Membrane，MFGM）が豊富に含まれており，MFGM は膜タンパク質とリン脂質を主成分とする複合物質から構成されている。我々は MFGM の食品機能性を見出す研究の一環で，アトピー様症状を発症させる条件で飼育した HR-1 マウスに MFGMを混餌で与えたところ，背部皮膚の経皮水分蒸散量（Transepidermal Water Loss，TEWL）の上昇抑制効果を見出した。この作用機序を明らかにするために皮膚の遺伝子発現解析を行った結果，皮膚バリア機能が異常な HR-1 マウスでは表皮の周辺帯構成遺伝子群が著しく増加しており，MFGMはその発現量を有意に減少させることを見出した。また，冬季の北海道で実施した肌荒れを実感している人を対象としたMFGMの摂取試験においても，TEWL の改善効果が見出された。以上の結果から，MFGMは周辺帯構成遺伝子群の過剰発現を正常化して皮膚のバリア機能を回復させる肌質改善効果を有していることが示唆された。