The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels have revolutionized our understanding of lipolysis. In this review, we focus on the mechanisms that facilitate intracellular fatty-acid mobilization, drawing on canonical and noncanonical enzymatic pathways. We summarize how intracellular lipolysis affects lipid-mediated signalling, metabolic regulation and energy homeostasis in multiple organs. Finally, we examine how these processes affect pathogenesis and how lipolysis may be targeted to potentially prevent or treat various diseases. Zechner and colleagues discuss mechanisms facilitating the mobilization of intracellular fatty acids and how they affect lipid-mediated signalling, metabolic regulation and energy homeostasis in health and disease.

Lipolysis: cellular mechanisms for lipid mobilization from fat stores.

Many consumers are interested in decreasing their consumption of animal products, such as bovine milk, because of health, environmental, and ethical reasons. The food industry is therefore developing a range of plant-based milk alternatives. These milk substitutes should be affordable, convenient, desirable, nutritional, and sustainable. This article reviews our current understanding of the development of plant-based milks. Initially, an overview of the composition, structure, properties, and nutritional profile of conventional bovine milk is given, because the development of successful alternatives depends on understanding the characteristics of real milk. The two main production routes for fabricating plant-based milks are then highlighted: (i) disruption of plant materials (such as nuts, seeds, or legumes) to form aqueous suspensions of oil bodies; (ii) formation of oil-in-water emulsions by homogenization of oil, water, and emulsifiers. The roles of the different functional ingredients in plant-based milks are highlighted, including oils, emulsifiers, thickeners, antioxidants, minerals, and other additives. The physicochemical basis of the appearance, texture, and stability of plant-based milks is covered. The importance of the sensory attributes and gastrointestinal fate of bovine milk and plant-based alternatives is also highlighted. Finally, potential areas for future work are discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1541-4337.12505

Plant-based Milks: A Review of the Science Underpinning Their Design, Fabrication, and Performance.

Human milk is uniquely optimized for the needs of the developing infant. Its composition is complex and dynamic, driven primarily by maternal genetics, and to a lesser extent by diet and environment. One important component that is gaining attention is the milk fat globule (MFG). The MFG is composed of a triglyceride-rich core surrounded by a tri-layer membrane, also known as the milk fat globule membrane (MFGM) that originates from mammary gland epithelia. The MFGM is enriched with glycerophospholipids, sphingolipids, cholesterol, and proteins, some of which are glycosylated, and are known to exert numerous biological roles. Mounting evidence suggests that the structure of the MFG and bioactive components of the MFGM may benefit the infant by aiding in the structural and functional maturation of the gut through the provision of essential nutrients and/or regulating various cellular events during infant growth and immune education. Further, antimicrobial peptides and surface carbohydrate moieties surrounding the MFG might have a pivotal role in shaping gut microbial populations, which in turn may promote protection against immune and inflammatory diseases early in life. This review seeks to: (1) understand the components of the MFG, as well as maternal factors including genetic and lifestyle factors that influence its characteristics; (2) examine the potential role of this milk component on the intestinal immune system; and (3) delineate the mechanistic roles of the MFG in infant intestinal maturation and establishment of the microbiota in the alimentary canal.

/pdf/compositional-dynamics-of-the-milk-fat-globule-and-its-role-49584elb01.pdf

Compositional Dynamics of the Milk Fat Globule and Its Role in Infant Development.

This review aims to provide an in depth overview of the current knowledge of the effects of bovine immunoglobulins on the human immune system. The stability and functional effects of orally ingested bovine immunoglobulins in milk products are described and potential mechanisms of action are discussed. Orally ingested bovine IgG (bovine IgG) can be recovered from feces, ranging from very low levels up to 50% of the ingested IgG that has passed through the gastrointestinal tract. In infants the recovered levels are higher than in adults most likely due to differences in stomach and intestinal conditions such as pH. This indicates that bovine IgG can be functionally active throughout the gastrointestinal tract. Indeed, a large number of studies in infants and adults have shown that bovine IgG (or colostrum as a rich source thereof) can prevent gastrointestinal tract infections, upper respiratory tract infections, and LPS-induced inflammation. These studies vary considerably in target group, design, source of bovine IgG, dosage, and endpoints measured making it hard to draw general conclusions on effectiveness of bovine immunoglobulin rich preparations. Typical sources of bovine IgG used in human studies are serum-derived IgG, colostrum, colostrum-derived IgG, or milk-derived immunoglobulins. In addition, many studies have used IgG from vaccinated cows, but studies using IgG from nonimmunized animals have also been reported to be effective. Mechanistically, bovine IgG binds to many human pathogens and allergens, can neutralize experimental infection of human cells, and limits gastrointestinal inflammation. Furthermore, bovine IgG binds to human Fc receptors which, enhances phagocytosis, killing of bacteria and antigen presentation and bovine IgG supports gastrointestinal barrier function in in vitro models. These mechanisms are becoming more and more established and explain why bovine IgG can have immunological effects in vivo. The inclusion of oral bovine immunoglobulins in specialized dairy products and infant nutrition may therefore be a promising approach to support immune function in vulnerable groups such as infants, children, elderly and immunocompromised patients.

/pdf/effects-of-bovine-immunoglobulins-on-immune-function-allergy-42ycjz1zwi.pdf

Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection.

Breastfeeding confers many benefits to the breast-fed infant which are reflected by better short-term and long-term outcomes as compared to formula-fed infants. Many components of breast milk are likely to contribute to these favorable outcomes, and there has recently been focus on the milk fat globule membrane (MFGM). This fraction is a heterogenous mixture of proteins (many of them glycosylated), phospholipids, sphingolipids, gangliosides, choline, sialic acid and cholesterol which is lacking in infant formula as milk fat (which is also low in these components) is replaced by vegetable oils. Many of these components have been shown to have biological effects, and there is considerable evidence from preclinical studies and clinical trials that providing bovine MFGM results in improved outcomes, in particular with regard to infections and neurodevelopment. Since bovine MFGM is commercially available, it is possible to add it to infant formula. There are, however, considerable variations in composition among commercial sources of bovine MFGM, and as it is not known which of the individual components provide the various bioactivities, it becomes important to critically review studies to date and to delineate the mechanisms behind the activities observed. In this review, we critically examine the preclinical and clinical studies on MFGM and its components in relation to resistance to infections, cognitive development, establishment of gut microbiota and infant metabolism, and discuss possible mechanisms of action.

Milk fat globule membrane: the role of its various components in infant health and development.

Scope Milk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study wasto determine whether supplementing MFGM in an infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies. Methods and results The serum metabolome and fecal microbiota wereanalyzed using 1 H NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM-enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula-fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation didnot induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota-associated metabolites. Conclusion Supplementing MFGM in a formula reduced some metabolic gaps between formula-fed and breastfed infants. This article is protected by copyright. All rights reserved.

Milk Fat Globule Membrane as a Modulator of Infant Metabolism and Gut Microbiota: A Formula Supplement Narrowing the Metabolic Differences between Breastfed and Formula-Fed Infants.

Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced mortality rates. GLU is poorly absorbed and may exhibit functional properties in the gut. The purpose of this study was to examine the impact of glucosamine on gastrointestinal function as well as changes in fecal microbiota and metabolome. Healthy males (n = 6) and females (n = 5) (33.4 ± 7.7 years, 174.1 ± 12.0 cm, 76.5 ± 12.9 kg, 25.2 ± 3.1 kg/m2, n = 11) completed two supplementation protocols that each spanned three weeks separated by a washout period that lasted two weeks. In a randomized, double-blind, placebo-controlled, crossover fashion, participants ingested a daily dose of GLU hydrochloride (3000 mg GlucosaGreen®, TSI Group Ltd., Missoula, MT, USA) or maltodextrin placebo. Study participants completed bowel habit and gastrointestinal symptoms questionnaires in addition to providing a stool sample that was analyzed for fecal microbiota and metabolome at baseline and after the completion of each supplementation period. GLU significantly reduced stomach bloating and showed a trend towards reducing constipation and hard stools. Phylogenetic diversity (Faith's PD) and proportions of Pseudomonadaceae, Peptococcaceae, and Bacillaceae were significantly reduced following GLU consumption. GLU supplementation significantly reduced individual, total branched-chain, and total amino acid excretion, with no glucosamine being detected in any of the fecal samples. GLU had no effect on fecal short-chain fatty acids levels. GLU supplementation provided functional gut health benefits and induced fecal microbiota and metabolome changes.

/pdf/impact-of-glucosamine-supplementation-on-gut-health-q9qx27xx3i.pdf

Impact of Glucosamine Supplementation on Gut Health.

This study builds on a previous study by this group in which 6–11-month-old Peruvian infants who were fed bovine milk fat globule membrane (MFGM) containing complementary food had significantly fewer episodes of infection-related bloody diarrhea relative to those consuming a control food (skim milk powder). Micronutrient deficiencies including zinc deficiency were prevalent in this study population. To understand the mechanism behind the health benefits of consuming MFGM, the serum metabolome and cytokine levels, as markers for systemic immune responses, were evaluated using 1H nuclear magnetic resonance-based metabolomics and a multiplex system, respectively. Combined with data on micronutrient status and anthropometry, a comparative analysis was performed. Supplementation with MFGM tended to improve micronutrient status, energy metabolism, and growth reflected as increased levels of circulating amino acids and weight gain, particularly in female infants compared to controls. Decreased levels of the microbial choline metabolite trimethylamine-N-oxide in the MFGM-supplemented group (both male and female infants) suggest a functional perturbation in the intestinal microbiota. A cytokine shift toward a less T helper type 1 response was observed in those receiving the MFGM supplement, which was mainly attributed to decreases in interleukin-2 levels. Our findings suggest that consumption of MFGM with complementary food may reverse the metabolic abnormalities found in marginally nourished infants, thereby improving metabolic regulation, which may lead to enhanced immunity. Bovine milk fat globule membrane (MFGM)-enriched complementary food has been recognized to be capable of reducing the episodes of bloody diarrhea in marginally nourished infants. However, the metabolic influence of MFGM remains unknown. Carolyn Slupsky from University of California-Davis and co-workers studied the impacts of bovine MFGM consumption on the levels of serum metabolome and immune markers. They found the supplements of MFGM improved the micronutrient status, energy metabolism, and growth, especially prominent for female infants. Moreover, MFGM complementary food lowered the level of the bacterial choline metabolite trimethylamine-N-oxide in the infants, indicating a functional perturbation to their intestinal microbiota. These findings suggest MFGM in complementary food can help to regulate the metabolic abnormalities of the infants with micronutrient deficiency, probably resulting in enhanced immunity.

/pdf/effect-of-bovine-milk-fat-globule-membranes-as-a-2pp8iia7qb.pdf

Effect of bovine milk fat globule membranes as a complementary food on the serum metabolome and immune markers of 6-11-month-old Peruvian infants

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Compositional Dynamics of the Milk Fat Globule and Its Role in Infant Development.

Milk Fat Globule Membrane as a Modulator of Infant Metabolism and Gut Microbiota: A Formula Supplement Narrowing the Metabolic Differences between Breastfed and Formula-Fed Infants.

Impact of Glucosamine Supplementation on Gut Health.

Effect of bovine milk fat globule membranes as a complementary food on the serum metabolome and immune markers of 6-11-month-old Peruvian infants