Effect of milk fat globules on growth and metabolism in rats fed an unbalanced diet.

We assessed the effects of supplementing milk fat globules (MFG) on the growth and development of the skeleton in rats fed a Western unbalanced diet (UBD). The UBD is high in sugar and fat, low in protein, fiber, and micronutrients, and negatively impacts health. The MFG-a complex lipid-protein assembly secreted into milk-has a unique structure and composition, which differs significantly from isolated and processed dietary ingredients. Rats consuming the UBD exhibited growth retardation and disrupted bone structural and mechanical parameters; these were improved by supplementation with small MFG. The addition of small MFG increased the efficiency of protein utilization for growth, and improved trabecular and cortical bone parameters. Furthermore, consumption of UBD led to a decreased concentration of saturated fatty acids and increased levels of polyunsaturated fatty acids (PUFA), particularly omega-6 PUFA, in the serum, liver, and adipose tissue. The addition of small MFG restored PUFA concentration and the ratio of omega-6 to omega-3 PUFA in bone marrow and adipose tissue. Finally, large but not small MFG supplementation affected the cecal microbiome in rats. Overall, our results suggest that natural structure MFG supplementation can improve metabolism and bone development in rats fed an UBD, with the effects depending on MFG size. Moreover, the benefits of small MFG to bone development and metabolism were not mediated by the microbiome, as the detrimental effects of an UBD on the microbiome were not mitigated by MFG supplementation.

Effect of Combined Protein-Enriched Enteral Nutrition and Early Cycle Ergometry in Mechanically Ventilated Critically Ill Patients-A Pilot Study.

BACKGROUND: Cycle ergometry (CE) is a method of exercise used in clinical practice. Limited data demonstrate its effectiveness in critically ill patients. We aimed to evaluate the combination of CE and a high-protein diet in critically ill patients. METHODS: This was an open label pilot trial comparing conventional physiotherapy with enteral nutrition (EN) (control, Group 1), CE with EN (Group 2), and CE with protein-enriched EN (Group 3). The primary outcome was length of ventilation (LOV). Secondary outcomes were intensive care unit (ICU) mortality, length of ICU stay (ICU LOS), length of hospital stay (Hospital LOS), and rate of re-intubation. RESULTS: Per protocol, 41 ICU patients were enrolled. Thirteen patients were randomized to Group 1 (control), fourteen patients to Group 2, and fourteen patients to Group 3 (study groups). We found no statistically significant difference in LOV between the study arms (14.2 ± 9.6 days, 15.8 ± 7.1 days, and 14.9 ± 9.4 days, respectively, p = 0.89). Secondary outcomes did not demonstrate any significant differences between arms. CONCLUSIONS: In this pilot trial, CE combined with either standard EN or protein-enriched EN was not associated with better clinical outcomes, as compared to conventional physiotherapy with standard EN. Larger trials are needed in order to further evaluate this combination.

Enteral and supplemental parenteral nutrition enriched with omega-3 polyunsaturated fatty acids in intensive care patients - A randomized, controlled, double-blind clinical trial.

BACKGROUND & AIMS: Enteral nutrition (EN) and parenteral nutrition (PN) enriched with omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects in critical illness. This study aimed to assess the combined effect of EN and supplemental PN enriched with omega-3 PUFA on blood oxygenation in intensive care unit (ICU) patients. METHODS: Single-center, prospective, randomized, controlled, double-blind, phase III trial conducted from 10/2013 to 11/2017. A total of 100 ICU patients (18-85 years, APACHE II score > 15) requiring mechanical ventilation were randomly assigned to received combined EN and PN either with omega-3 PUFA (omega-3 group) or without (control group) for up to 28 days. Primary endpoint: 'change of PaO2/FiO2 from day (D) 1 to D4'. Secondary endpoints: lung function parameters, ICU complications, length of hospital stay, days free of ICU care/ventilation/sedation/catecholamine treatment, mortality, erythrocyte fatty acid composition, inflammatory parameters. Safety parameters: standard laboratory assessment, vital signs, physical examination, SOFA score, adverse events. RESULTS: Combined EN and PN covered energy requirements to more than 80%. Blood oxygenation (ΔPaO2/FiO2 from D1 to D4: -1.3 ± 83.7, n = 42, and 13.3 ± 86.1, n = 39, in omega-3 and control group, respectively, p = 0.7795) and other lung function parameters did not differ between groups but days free of catecholamine treatment were significantly higher in the omega-3 group (~4 days, p = 0.0481). On D6, significantly more patients in the omega-3 group tolerated EN alone (51.0% vs. 29.8%, p = 0.0342). Eicosapentaenoic acid (EPA) content in erythrocytes was significantly increased in the omega-3 group at last observation compared with the control group (ΔEPA: 0.928 ± 0.808% vs. -0.024 ± 0.190%, p < 0.0001). No further significant group differences were detected. CONCLUSIONS: Enteral and supplemental PN both enriched with omega-3 PUFA did not improve lung function but allowed earlier weaning from catecholamine treatment and PN. Supplemental PN succeeded to adequately cover energy requirements in critically ill patients. TRIAL REGISTRATION: www.clinicaltrials.gov, registration number: NCT01162928.

Lipidome changes, with a focus on phospholipids, due to feeding systems and processing in goat milk.

We evaluated the effects of processing - pasteurization and yoghurt manufacturing - on some health-promoting lipidome components in milk from two feeding treatments - brushland grazing or hay-feeding in confinement - in dairy goats. The contents of fat and protein were higher, and of urea, lower, in grazing goats. Fatty acid composition - at the exception of saturated fatty acids - was affected by dietary management and milk processing. Phospholipid contents was lower in confined goats, with little effect for processing. The phospholipid-to-triglyceride ratio was decreased by pasteurization. Sensitivity to pasteurization of phospholipid composition differed between feeding treatments. The percentage of sphingomyelin increased following pasteurization, with no response for fermentation to yoghurt. These results can be exploited to modulate health-promoting fats in dairy products.

Effect of Supplemental Enteral Fish Oil on the Development of Psychological Complications in Critically Ill Multiple-Trauma Patients: 6 Months' Follow-Up.

BACKGROUND: Posttraumatic stress disorder (PTSD) is common in intensive care unit (ICU) patients. Defic it intake of ω-3 polyuns aturated fatty ac ids (PUFAs) may be as sociated with developm ent of PTSD. METHODS: This study randomized mechanically ventilated patients suffering from multiple trauma (n = 150) into 2 groups: a study and a control group that received enteral feeding with or without fish oil. Fifty-one patients were interviewed 6 months after discharge from the ICU. Psychometric parameters of PTSD were assessed by questionnaires. The fatty acid composition of erythrocyte membranes was performed by homogenization of the cells in hexane-isopropanol. RESULTS: No differences were found in baseline characteristics between the groups. Erythrocyte membrane composition showed significantly higher concentrations of ω-3 fatty acids in the study group. Anxiety and depression symptoms were correlated with an increase in eicosapentaenoic acid (EPA) on days 4 and 8 for depression and EPA on day 4 and docosahexaenoic acid (DHA) on day 8 for anxiety. Total ω-3 content was positively correlated with anxiety and depression as well. An inverse correlation was found between DHA and EPA in the treatment group and with the total ω-3 and DHA in the control group for the Brief Illness Perceptions Questionnaire. CONCLUSION: Administration of an ω-3 PUFA-enriched diet during the ICU stay did not prevent development of PTSD in trauma patients 6 months after discharge from ICU.

The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development.

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.

Dietary pomegranate peel improves milk quality of lactating ewes: Emphasis on milk fat globule membrane properties and antioxidative traits.

Concentrated pomegranate peel extract (CPE) was supplemented to ewes, and milk yield and fat content-fatty acid (FA) and phospholipid (PL) composition-were monitored. CPE-fed ewes had higher milk yield, and fat, protein and lactose contents than controls. Milk PL content-20% higher in the CPE-supplemented group-was regulated by treatment and not by total fat content; milk phosphatidylethanolamine and phosphatidylcholine increased by 22 and 26%, respectively, in CPE-supplemented vs. control ewes. Milk saturated FA concentration was higher, and total polyunsaturated and monounsaturated FA content lower in the CPE vs. control group, regardless of milk total fat content. CPE supplementation increased milk antioxidant capacity, suggesting antioxidant transfer from dietary source to milk, increasing stability and nutritive value. Our study provides first evidence for milk quality improvement in terms of antioxidants and PL enrichment without compromising total milk fat, suggesting strategies to improve dairy animals' milk composition without compromising total production.

Telomere Length Changes during Critical Illness: A Prospective, Observational Study.

OBJECTIVE: evaluation of telomere length change in acutely ill adult patients. DESIGN: Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APACHE II scores. Additional data collected during the ICU stay included a repeated WBC count, the presence of positive blood cultures and outcome data, including death in the ICU or following discharge, whether ventilated or not at ICU discharge, and destination following discharge, i.e., medical ward or rehabilitation. SETTING: General ICU in tertiary hospital. PATIENTS: Forty patients admitted to the ICU within 72 h of hospital admission suffering from an acute illness were included in this prospective, observational study. MAIN RESULTS: Of the 40 patients studied, telomere shortening was noted in 21, telomere lengthening in 11, and no significant change in the other eight. The age of patients demonstrating telomere shortening was statistically significantly younger (45.4 vs. 61.5 years, p < 0.023) compared to those showing increased telomere length. In addition, a significant correlation was observed between the difference in telomere length and the corresponding difference in WBC count (telomere shortening was associated with a decreased WBC count and vice versa). A trend toward shortening was seen in patients with sepsis (p = 0.07). No significant correlations were found for any other demographic or outcome parameter and changes in telomere length. CONCLUSION: Changes in telomere length, both shortening and lengthening, were evident in the acute setting, but no associations between such changes with outcome were noted. Further studies in more homogeneous groups of patients appear to be warranted.

Changes in lipid droplets morphometric features in mammary epithelial cells upon exposure to non-esterified free fatty acids compared with VLDL.

The effects of the macrostructure of long chain fatty acids on the lipid metabolism and biosynthesis of lipid droplets (LD) was studied in mammary epithelial cells (MEC). MEC were exposed to similar compositions and concentrations of fatty acids in the form of either triglycerides (Tg), as part of the very-low-density lipids (VLDL) isolated from lactating cow plasma, or as non-esterified- free fatty acids (FFA). Exposing MEC to FFA resulted in two distinct processes; each independently could increase LD size: an elevation in Tg production and alterations in phospholipid (PL) composition. In particular, the lower PC/PE ratio in the FFA treatment indicated membrane destabilization, which was concomitant with the biosynthesis of larger LD. In addition, 6 fold increase in the cellular concentration of the exogenously added linoleic acid (C18:2) was found in MEC treated with FFA, implying that long chain fatty acids administrated as FFA have higher availability to MEC, enabling greater PL synthesis, more material for the LD envelope, thereby enhancing LD formation. Availability of long chain fatty acids administrated as VLDL-Tg, is dependent on LPL which its activity can be inhibited by the hydrolysis products. Therefore, we used increasing concentrations of albumin, to reduce the allosteric inhibition on LPL by the hydrolysis products. Indeed, a combined treatment of VLDL and albumin, increased LD size and number, similar to the phenotype found in the FFA treatment. These results reveal the role played by the macrostructure of long chain fatty acids in the regulation of LD size in MEC which determine the size of the secreted MFG.

Altered concentrate to forage ratio in cows ration enhanced bioproduction of specific size subpopulation of milk fat globules.

The mechanism underlying the shift in milk-fat-globule (MFG) mean diameter upon changing the concentrate-to-forage ratio in dairy cow rations was investigated. Cows were fed high-concentrate low-forage (HCLF) or high-forage low-concentrate (LCHF) rations for 4 weeks. Mean diameter of MFG, determined in raw whole milk, was 0.4 µm larger in the LCHF-fed vs. HCLF-fed group. The main compositional differences between treatments were found in a specific MFG subgroup with the diameter of 3.3 µm (F1), with higher capric, lauric, myristic and lower oleic acid concentrations in HCLF vs. LCHF milk. Similarly, lipid concentration differences between treatments were only found in F1, with higher triglyceride and phosphatidylethanolamine, and lower sphingomyelin concentrations in LCHF vs. HCLF milk. The higher MFG mean diameter in whole raw LCHF milk might therefore be attributed to increased secretion of F1-group MFG, while fat content and composition in the other MFG size groups remains unchanged.

Elevated concentrate-to-forage ratio in dairy cow rations is associated with a shift in the diameter of milk fat globules and remodeling of their membranes.

We examined the effects of concentrate-to-forage ratio in dairy cow rations on milk-fat composition, with a specific focus on the structure of milk fat globules (MFG). Twenty-four Holstein cows, 153 d in milk, were assigned to 2 dietary treatments in a crossover design study. Treatments were (1) high-concentrate (65%), low-forage (35%; HCLF) diet and (2) low-concentrate (35%), high-forage (65%; LCHF) diet. The mean diameter of the MFG; plasma concentrations of insulin, glucose, and nonesterified fatty acids (FA); and the composition and concentrations of milk FA and polar lipids were determined. Concentrations of insulin were 56% higher, and those of nonesterified FA 46% lower, in the HCLF than in the LCHF diet. The milk yield was 8.5 kg/d higher and yields of fat, protein, and lactose were 180, 350, and 403 g/d higher, respectively, in the HCLF versus LCHF diet. Milk FA composition differed between treatments, with 1.5 and 1.0 percentage units higher saturated and polyunsaturated FA concentrations, respectively, in the HCLF versus LCHF diet. Mean MFG diameter tended to be smaller (0.2 µm) in the HCLF diet than in the LCHF diet, associated with increased daily phospholipids yield (34%), lower phosphatidylserine and higher phosphatidylcholine concentrations. In conclusion, the decreased milk and fat yields in the LCHF diet were associated with remodeling of the MFG membrane and with the secretion of larger MFG. Membrane remodeling of the mammary epithelium membranes seems to play a role in regulating MFG size.

The relationship between size and lipid composition of the bovine milk fat globule is modulated by lactation stage.

The effect of lactation stage and size on the lipid composition of bovine milk fat globules (MFG) and their membranes (MFGM) was investigated. MFG were separated into six size groups (1-3 µm) from samples collected in early, mid and late lactation stages (10-250 days postpartum). Fatty acid and polar lipid composition was determined in each size group, at each lactation stage. PUFA concentration was affected by lactation stage but not MFG size. Saturated fatty acid concentration at 60 days postpartum was 10% higher in small vs. large globules. Phosphatidylcholine and cholesterol followed the same concentration pattern throughout lactation in all MFG size groups. From day 100 postpartum on, phosphatidylethanolamine concentration was constant in the large MFG, but dropped twofold in the small MFG. Results suggest distinct compositional regulation for large and small MFG at different lactation stages. Such interactions between structure, composition and lactation stage may be exploited for human milk and dairy product consumption.

Size-dependent lipid content of bovine milk fat globule and membrane phospholipids.

The mammary epithelial cell produces unique structures and a range of diversely sized lipid particles from tens of micrometers to less than 1 µm. The physical, chemical, and biological properties of the differently sized milk fat globules (MFGs) and their complex membranes are not well described. Six size fractions of MFGs were obtained by gravity-based separation and analyzed, and their partial lipidome was determined. The smallest MFGs had a higher concentration of polyunsaturated fatty acids (FAs). The FAs indicative of elongase activity were highest in the smallest MFGs, whereas those FAs indicative of desaturase activity did not differ between size groups. The phosphatidylinositol concentration was highest whereas the phosphatidylserine concentration was lowest in MFGs with an average diameter of 2 µm. Phosphatidylethanolamine and cholesterol concentrations were highest whereas that of sphingomyelin was lowest in MFGs with an average diameter of 3 µm. Phosphatidylcholine concentrations did not vary between the size groups. Results suggest that the assembly of milk fat globules that differ in size is not a homogeneous nor random process and that the differences in composition may reflect discrete biosynthetic routes.