Whey Protein Components - Lactalbumin and Lactoferrin - Improve Energy Balance and Metabolism.
ABSTRACT: Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of ?-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.
Project description:The antiviral activity of native and esterified whey proteins fractions (alpha-lactalbumin, beta-lactoglobulin, and lactoferrin) was studied to inhibit tomato yellow leaf curl virus (TYLCV) on infected tomato plants. Whey proteins fractions and their esterified derivatives were sprayed into TYLCV-infected plants. Samples were collected from infected leaves before treatment, 7 and 15 days after treatment for DNA and molecular hybridization analysis. The most evident inhibition of virus replication was observed after 7 and 15 days using alpha-lactoferrin and alpha-lactalbumin, respectively. Native and esterified lactoferrin showed complete inhibition after 7 days. On the other hand, native beta-lactoglobulin showed inhibition after 7 and 15 days whereas esterified beta-lactoglobulin was comparatively more effective after 7 days. The relative amount of viral DNA was less affected by the esterified alpha-lactalbumin whereas native alpha-lactalbumin inhibited virus replication completely after 15 days. These results indicate that native or modified whey proteins fractions can be used for controlling the TYLCV-infected plants.
Project description:BACKGROUND:Protein quality evaluation aims to determine the capacity of food sources and diets to meet protein and indispensable amino acid (IAA) requirements. This study determined whether nitrogen balance was affected and whether dietary IAA were adequately obtained from the ad libitum consumption of diets at three levels of protein from different primary sources for 12 days. METHODS:Two 12-day randomized crossover design trials were conducted in healthy subjects [n?=?70/67 (M/F); age: 19-70 y; BMI: 18.2-38.7 kg/m(2)]. The relative dietary protein content was lower than [5% of energy (En%)], similar to (15En%), and higher than (30En%) customary diets. These diets had a limited variety of protein sources, containing wheat protein as a single protein source (5En%-protein diet) or 5En% from wheat protein with 10En% (15En%-protein diets) or 25En% (30En%-protein diets) added from whey with ?-lactalbumin, soy or beef protein. RESULTS:There was a dose-dependent increase in nitrogen excretion with increasing dietary protein content, irrespective of the protein sources (P?=?0.001). Nitrogen balance was maintained on the 5En%-protein diet, and was positive on the 15En%- and 30En%-protein diets (P?<?0.001) over 12 days. Protein intake from the 5En%-protein diet did not reach the amount necessary to meet the calculated minimal IAA requirements, but IAA were sufficiently obtained from the 15En%- and 30En%-protein diets. In the 15En%- and 30En%-protein conditions, a higher protein intake from the soy-containing diets than from the whey with ?-lactalbumin or beef containing diets was needed to meet the minimal IAA requirements. CONCLUSION:Protein intake did not compensate for an insufficient indispensable amino acid intake with a low-protein diet for 12 days. TRIAL REGISTRATION:These trials were registered at clinicaltrials.gov as NCT01320189 and NCT01646749.
Project description:BACKGROUND:Avian influenza A (H5N1) virus is one of the most important public health concerns worldwide. The antiviral activity of native and esterified whey proteins fractions (?- lactalbumin, ?- lactoglobulin, and lactoferrin) was evaluated against A/chicken/Egypt/086Q-NLQP/2008 HPAI (H5N1) strain of clade 2.2.1 (for multiplicity of infection (1 MOI) after 72 h of incubation at 37 °C in the presence of 5% CO?) using MDCK cell lines. RESULT:Both the native and esterified lactoferrin seem to be the most active antiviral protein among the tested samples, followed by ?- lactoglobulin. ?-Lactalbumin had less antiviral activity even after esterification. CONCLUSION:Esterification of whey proteins fractions especially lactoferrin and ?-lactoglobulin enhanced their antiviral activity against H5N1 in a concentration dependent manner.
Project description:The N-linked glycoprofile of bovine whey is the combined result of individual protein glycoprofiles. In this work, we provide in-depth structural information on the glycan structures of known whey glycoproteins, namely, lactoferrin, lactoperoxidase, ?-lactalbumin, immunoglobulin-G (IgG), and glycosylation-dependent cellular adhesion molecule 1 (GlyCAM-1, PP3). The majority (?95%) of <i>N</i>-glycans present in the overall whey glycoprofile were attributed to three proteins: lactoferrin, IgG, and GlyCAM-1. We identified specific signature glycans for these main proteins; lactoferrin contributes oligomannose-type glycans, while IgG carries fucosylated di-antennary glycans with Gal-?(1,4)-GlcNAc (LacNAc) motifs. GlyCAM-1 is the sole whey glycoprotein carrying tri- and tetra-antennary structures, with a high degree of fucosylation and sialylation. Signature glycans can be used to recognize individual proteins in the overall whey glycoprofile as well as for protein concentration estimations. Application of the whey glycoprofile analysis to colostrum samples revealed dynamic protein concentration changes for IgG, lactoferrin, and GlyCAM-1 over time.
Project description:Diets deficient in protein often increase food consumption, body weight and fat mass; however, the underlying mechanisms remain poorly understood. We compared the effects of diets varying in protein concentrations on energy balance in obesity-prone rats. We demonstrate that protein-free (0% protein calories) diets decreased energy intake and increased energy expenditure, very low protein (5% protein) diets increased energy intake and expenditure, whereas moderately low protein (10% protein) diets increased energy intake without altering expenditure, relative to control diet (15% protein). These diet-induced alterations in energy expenditure are in part mediated through enhanced serotonergic and ?-adrenergic signaling coupled with upregulation of key thermogenic markers in brown fat and skeletal muscle. The protein-free and very low protein diets decreased plasma concentrations of multiple essential amino acids, anorexigenic and metabolic hormones, but these diets increased the tissue expression and plasma concentrations of fibroblast growth factor-21. Protein-free and very low protein diets induced fatty liver, reduced energy digestibility, and decreased lean mass and body weight that persisted beyond the restriction period. In contrast, moderately low protein diets promoted gain in body weight and adiposity following the period of protein restriction. Together, our findings demonstrate that low protein diets produce divergent effects on energy balance.
Project description:Deletion or mutation of SH2B1 (SH2-B, PSM) is associated with severe obesity and insulin resistance in mice and humans. SH2B1 is alternatively spliced into four known isoforms: a, b, g, and d. Contrasting the ubiquitous expression of SH2B1b and g, SH2B1a and d are expressed almost exclusively in brain. Here, we generated mice lacking the brain-specific SH2B1 isoforms (SH2B1adKO mice). SH2B1adKO mice are protected from weight gain on standard and high fat diets, a phenotype caused by hypophagia. SH2B1adKO mice exhibit improvements in glucose homeostasis, yet these are mostly adiposity-dependent. Surprisingly, SH2B1adKO mice demonstrate normal leptin sensitivity. RNA sequencing highlights potential mechanisms underlying the decreased appetite of SH2B1adKO mice including gene expression changes associated with neuronal synapses. These findings suggest that SH2B1a and/or d are key regulators of energy balance. Furthermore, they highlight the profound importance of alternative splicing regulation for body weight.
Project description:The balance between free radicals and antioxidants is an important factor for maintaining health and slowing disease progression. The use of antioxidants, particularly natural antioxidants, has become an important strategy for dealing with this cause of widespread diseases. Natural antioxidants have been used as therapeutic tools against many diseases because they are safe, effective, and inexpensive and are among the most commonly used adjuvants in the treatment of several diseases. Camel whey protein (CWP) is considered a strong natural antioxidant because it decreases oxidative stress, enhances immune system function, and increases glutathione levels. The structure of CWP is very similar to that of other types of whey protein from different types of milk. CWP contains many components, such as lactoferrin (LF), lactalbumin, lactoglobulins, lactoperoxidase, and lysozyme, and is rich in immunoglobulins. However, in contrast to other WPs, CWP lacks β-lactoglobulin, the main cause of milk allergies in children. The components of CWP have many beneficial effects, including stimulation of both innate and adaptive immunity and anti-inflammatory, anticancer, antibacterial, and antiviral activities. Recently, it has been shown that CWP and its unique components can facilitate the treatment of impaired diabetic wound healing. However, the molecular mechanisms underlying the protective effects of CWP in human and other animal disorders are not fully understood. Therefore, the current review presents a concise summary of the scientific evidence of the beneficial effects of CWP to support its therapeutic use in disease treatment and nutritional intervention.
Project description:The mammalian target of rapamycin (mTOR) kinase is a key regulator of several cellular functions, including cell growth and differentiation. Because hypothalamic mTOR complex 1 (mTORC1) signaling has been implicated as a target of leptin in the regulation of energy balance, we investigated its role in obesity-induced leptin resistance. In contrast to rats maintained on a low-fat (LF) diet for 3 weeks, rats maintained on a high-fat (HF)-diet had no anorexic response to intracerebroventricular leptin. Western blot analysis revealed that leptin was unable to modulate hypothalamic mTORC1 signaling in the HF group, whereas it significantly induced phosphorylation of both S6 kinase 1 (S6K1) and S6 ribosomal protein (S6) in the LF group. Similar to leptin, the cytokine ciliary neurotrophic factor (CNTF) induces hypophagia and increases signal transduction activator of transcription 3 phosphorylation. However, CNTF and its analog CNTF(Ax15) activate leptin-like pathways in the hypothalamus, even in leptin-resistant states, including diet-induced obesity. Intracerebroventricular CNTF(Ax15) decreased 24 h food intake and body weight in rats on HF or LF diets and increased the phosphorylation of hypothalamic S6K1 and S6 in a comparable way in both diets. Importantly, mice lacking the expression of S6K1 (S6K1(-/-)) did not respond to the anorectic action of either leptin or CNTF(Ax15), implying a crucial role for S6K1 in modulating the actions of these two cytokines. Finally, exposure to HF diet decreased mTORC1 signaling within the hypothalamus. Overall, these findings point strongly to the possibility that reduced hypothalamic mTORC1 signaling contributes to the development of hyperphagia, weight gain, and leptin resistance during diet-induced obesity.
Project description:Homogeneous rat alpha-lactalbumin was prepared from whey by chromatography on DEAE-Sephadex A-50 and Ultrogel AcA 44. Two biologically active forms of alpha-lactalbumin were apparent after ion-exchange chromatography, but on gel filtration the combined forms were eluted as a single peak with a molecular weight of approx. 33000. The molecular weight when determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis was 15100. Antiserum to alpha-lactalbumin was prepared from rabbits, and single radial immunodiffusion was used to measure the concentration of alpha-lactalbumin in milk expressed from rats during lactation and for 2 days after the cessation of lactation. A significant positive correlation (r = + 0.89) between the concentrations of alpha-lactalbumin and lactose was obtained for the first 20 days of lactation. This is consistent with the suggestion that alpha-lactalbumin may control the concentration of lactose in milk. However, a significant negative correlation (r = -0.91) between the concentration of alpha-lactalbumin and lactose was obtained for 2 days after the cessation of lactation on day 20.
Project description:Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ER?) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC.