Adipose tissue homeostasis orchestrates the oxidative, energetic, metabolic and endocrine disruption induced by binge drinking in adolescent rats.

Binge drinking (BD) is the most common alcohol consumption model for adolescents, and has recently been related to the generation of high oxidation and insulin resistance (IR). White adipose tissue (WAT) is a target organ for insulin action that regulates whole-body metabolism by secreting adipokines. The present study aimed to analyse the oxidative, inflammatory, energetic and endocrine profile in the WAT of BD-exposed adolescent rats, to obtain an integrative view of insulin secretion and WAT in IR progression. Two groups of male adolescent rats were used: control (n = 8) and BD (n = 8). An intermittent i.p. BD model (20% v/v) was used during 3 consecutive weeks. BD exposure led to a pancreatic oxidative imbalance, which was joint to high insulin secretion by augmenting deacetylase sirtuin-1 (SIRT-1) pancreatic expression and serum adipsin levels. However, BD rats had hyperglycaemia and high homeostasis model assessment of insulin resistance value (HOMA-IR). BD exposure in WAT increased lipid oxidation, as well as decreased insulin receptor substrate 1 (IRS-1) and AKT expression, sterol regulatory element-binding protein 1 (SREBP1), forkhead box O3A (FOXO3a) and peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte size. BD also affected the expression of proteins related to energy balance, such as SIRT-1 and AMP activated protein kinase (AMPK), affecting the adipokine secretion profile (increasing resistin/adiponectin ratio). BD altered the entire serum lipid profile, increasing the concentration of free fatty acids. In conclusion, BD led to an oxidative imbalance and IR process in WAT, which modified the energy balance in this tissue, decreasing the WAT lipogenic/lipolytic ratio, affecting adipokine secretion and the systemic lipid profile, and contributing to the progression of IR. Therefore, WAT is key in the generation of metabolic and endocrine disruption after BD exposure during adolescence in rats. KEY POINTS: Adolescent rat binge drinking (BD) exposure leads to hepatic and systemic oxidative stress (OS) via reactive oxygen species generation, causing hepatic insulin resistance (IR) and altered energy metabolism. In the present study, BD exposure in adolescent rats induces OS in the pancreas, with increased insulin secretion despite hyperglycaemia, indicating a role for IR in white adipose tissue (WAT) homeostasis. In WAT, BD produces IR and an oxidative and energetic imbalance, triggering an intense lipolysis where the serum lipid profile is altered and free fatty acids are increased, consistent with liver lipid accumulation and steatosis. BD exposure heightens inflammation in WAT, elevating pro-inflammatory and reducing anti-inflammatory adipokines, favouring cardiovascular damage. This research provides a comprehensive view of how adolescent BD in rats impacts liver, WAT and pancreas homeostasis, posing a risk for future cardiometabolic complications in adulthood.

Fermented goat's milk modulates immune response during iron deficiency anemia recovery.

BACKGROUND: Iron deficiency and iron overload can affect the normal functioning of the innate and adaptive immune responses. Fermented milk products may enhance immune functions, but little is known about the effect of fermented milks on modulation of the immune response during iron deficiency anemia and recovery with normal or high dietary iron intake. Eighty male Wistar rats were randomly assigned to a control group fed a standard diet or to an anemic group fed a diet deficit in iron. Control and anemic groups were fed for 30 days with diets based on a fermented goat's or cow's milk product, with normal iron content or iron overload. RESULTS: In general, during anemia recovery lectin and alternative complement pathway activity and lactoferrin decreased, because it improves iron homeostasis, which is critically important in immune system functions. Fermented goat's milk diet enhanced immune function during iron deficiency recovery, suppressed oxidant-induced eotaxin and fractalkine expression due to the concurrent reduction of free radical production and pro-inflammatory cytokines, and decreased monocyte chemoattractant protein-1 and monocyte migration and adhesion. The increase in interferon-γ can confer immunological colonization of gut microbiota and downregulate inflammation. CONCLUSION: Fermented goat's milk consumption enhances immune function, modifying complement pathway activity and decreasing pro-inflammatory cytokines as well as lactoferrin concentration, due to the improvement of iron homeostasis, which is critically important in the normal function of the immune system. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Oxidative stress, DNA stability and evoked inflammatory signaling in young celiac patients consuming a gluten-free diet.

PURPOSE: Celiac disease (CD) is a multifactorial, autoimmune, gluten-sensitive inflammatory disorder of the small intestine. Taking into account the pathogenesis of CD, a strict gluten-free diet (GFD) is the only treatment able to restore epithelium integrity and eliminate complications. The current study was designed to assess whether the use of a GFD is sufficient for maintaining a correct oxidative/antioxidant balance and ameliorating the evoked inflammatory signaling in young patients with CD. METHODS: The study covered 80 children, aged between 7 and 18 years, attending the Gastroenterology Service of the Gastroenterology, Hepatology and Child Nutrition Service from the Virgen de las Nieves Hospital in Granada. Children with CD diagnosed were included in the celiac group who followed a strict GFD for 2 years (n = 40) and the control group (n = 40) included healthy children, with negative serological screening. Soluble superoxide dismutase 1 and 2, total antioxidant status, 8-hydroxy-2'-deoxyguanosine, cortisol, melatonin and inflammatory parameters in plasma, 15-F2t-isoprostanes in urine, and DNA breaks in peripheral blood lymphocytes were analysed. RESULTS: No differences were found in oxidative stress between CD patients and controls; however, IFN-γ, IL-1α, IP-10 and TNF-ß were higher in the CD patients. VEGF was also higher than in the control group. CONCLUSION: The GFD in the CD patients is enough to reduce the oxidative stress; however, in the case of the inflammatory signaling, the initial exposure to gluten prior to stablish the GFD is strong enough to induce an inflammatory state which is maintained (even when consuming the GFD); meanwhile the increase in VEGF recorded in the CD group could be a compensatory mechanism to restore the damaged mucosa and duodenal villous atrophy, due to its role in endothelial activation and generation of new functional and stable vascular networks.

Association of sedentary time and physical activity levels with immunometabolic markers in early pregnancy: The GESTAFIT project.

OBJECTIVES: To analyze the association of sedentary time and physical activity (PA) intensity levels with immunometabolic markers during early pregnancy; and to examine if meeting the PA recommendations is associated with the immunometabolic profile of pregnant women. METHODS: Fifty Caucasian pregnant women (age: 32.8 ± 4.7 years old, body mass index: 24.2 ± 4.1kg/m2 , gestational age: 17 ± 1.5weeks) participated in this cross-sectional study (from September 2015 through May 2016). Sedentary time and PA intensity levels were objectively measured with triaxial accelerometer (seven consecutive valid days). Fasting serum glucose, total cholesterol, phospholipids, and triglycerides were assessed with standard methods. Serum pro-inflammatory and anti-inflammatory cytokines (fractalkine, interleukin-1ß, interleukin-6, interleukin-8, interleukin-10, interferon-γ, and tumor necrosis factor-α) were measured using Luminex xMAP technology. RESULTS: Sedentary time and PA were not correlated with any glycemic or lipid marker (P > .05). After adjusting for the potential confounders, vigorous PA showed a positive non-significant association with interleukin-6 (P = .06), and bouts of moderate-vigorous PA was inversely associated with interleukin-1ß and interferon-γ (P = .02 and P = .04, respectively). Meeting the PA guidelines was inversely associated with interleukin-1ß and positively associated with interleukin-8 (P = .01 and P = .04, respectively). These associations disappeared after controlling for multiplicity. CONCLUSIONS: Increasing the time spent in moderate-vigorous PA, or meeting the PA recommendations, is associated with the cytokine profile of women without metabolic disruptions in early pregnancy. However, sedentary time and PA do not seem to be associated with glucose or lipid levels. These results should be interpreted cautiously in view of the discrepancies after adjusting for multiple comparisons. Future studies in this novel field of research are warranted before reaching any conclusion.

High- and low- selenium diets affect endocrine energy balance during early programming.

High- and low- Se diets received by dams during gestation and lactation are related to insulin resistance in their pups. High-Se diet leads to an increase in serum insulin levels, which does not function properly, and an anabolic process. Low-Se diet is related to very low insulin values and an extreme catabolic energy imbalance. Selenoproteins have been implicated directly in the general endocrine regulation of appetite and energy homeostasis. To obtain information concerning how Se intake by dams is involved in regulating endocrine energy balance in progeny, three experimental groups of dam rats were used: control (Se: 0.1 ppm), Se-supplemented (Se: 0.5 ppm) and Se-deficient (Se: 0.01 ppm). At the end of lactation (21d old), the pups' appetite profile, Se levels, peptides from gastrointestinal tract (including pancreas), leptin, thyroid hormones, skeletal growth markers and cytokines in serum were measured. Low-Se diet leads to severe growth retardation, underdeveloped glands, a non-functional pancreas, non-operative high serum leptin levels and low GIT-anorexigenic signals. High-Se diet leads to non-operative high insulin secretion, obesity, inflammation and low leptin levels. These results point to Se as an important marker and a possible dietary supplementation treatment for gestating and lactating mothers in order to avoid metabolic disorders such as gestational diabetes or intrauterine growth retardation which could affect their progeny's future health in adulthood.

Enhancement of immune response mediated by oropharyngeal colostrum administration in preterm neonates.

BACKGROUND: The immune system of preterm infants is immature, being a significant cause of morbidity and mortality, particularly in the preterm infant. Oropharyngeal colostrum administration could be an immunomodulatory aid. Our aim was to evaluate the effect of oropharyngeal colostrum on the serum levels of immunoglobulins, lactoferrin, and resistin during the first month of life and to track the clinical outcome of the neonates. METHODS: One hundred preterm neonates born at <32 weeks of gestation and/or weighing < 1500 g and assisted in the Neonatal Intensive Care Unit were enrolled and divided into two groups: colostrum (n = 48) and control (n = 52). The subjects assigned to the colostrum group received 0.2 mL of colostrum (oropharyngeal route) every 4 hours for the first 15 days of life, and if mothers have inability to breastfeed, they were included in the control group (no oropharyngeal colostrum). Serum concentrations of IgA, IgM, and IgG1, lactoferrin, and resistin were assessed in both groups at 1, 3, 15, and 30 days of life. Clinical data during hospitalization were collected. RESULTS: IgA and IgM increased in preterm neonates who were administered colostrum for 15 and 30 days. Lactoferrin increased after 30 days, and resistin increased after 15 days of supplying oropharyngeal colostrum. The colostrum group underwent full enteral nutrition before, and no differences were observed in the common neonatal morbidities. CONCLUSION: Oropharyngeal colostrum administration is safe in preterm neonates and improves their immunologic profile, showing a potential role as an immunomodulatory agent.

Fermented goat milk consumption improves cardiovascular health during anemia recovery.

BACKGROUND: Iron (Fe) plays a crucial role in several fundamental processes, including erythropoiesis, cellular metabolism, and in cardiovascular disease. The aim of this work was to contribute to a better understanding of the physiology of and recovery from Fe deficiency by studying how fermented milk consumption affects vascular biomarkers during Fe repletion. RESULTS: The deleterious cardiovascular biomarkers cytokine-induced neutrophil chemoattractant 1, connective tissue growth factor (CTGF), interleukin-6, monocyte chemoattractant protein-1 (MCP-1), inhibitor of tissue plasminogen activator 1 total, metallopeptidase inhibitor 1 (TIMP-1), tumor necrosis factor alpha, vascular endothelial growth factor (VEGF), sE-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1) decreased after fermented goat milk consumption in groups of fed animals either with normal Fe or Fe overload with respect to rats fed with fermented cow milk. The beneficial cardiovascular biomarkers caveolin-1 and adiponectin were higher in both control and anemic rats fed fermented goat milk either with normal Fe or Fe overload with respect to fermented cow milk. Anemia decreased TIMP-1 in rats fed fermented goat milk with Fe overload, whereas there was increased CTGF and MCP-1 in animals fed fermented cow milk with either normal or Fe overload. In addition, Fe overload increased VEGF. CONCLUSION: Fermented goat milk consumption improves hematological status and promotes beneficial metabolic responses, which may attenuate cardiovascular risk factors during anemia recovery and iron overload to lessen the inflammatory response, macrophages activation and atherosclerosis development. © 2018 Society of Chemical Industry.

Fermented goat milk consumption during anaemia recovery: ergogenic effect and improvement of skeletal muscle homeostasis.

PURPOSE: Anaemia is associated with fatigue and diminished muscular oxygenation, which may affect skeletal muscle (SM). No studies are available about the SM modifications during anaemia recovery; therefore, the aim of this study is to study SM homeostasis during anaemia recovery with fermented milks. METHODS: Forty male Wistar rats were placed on a pre-experimental period of 40 days, divided in two groups (control group receiving normal-Fe diet and Fe-deficient group receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk-based diets, with normal-Fe content during 30 days. After feeding the fermented milks, leptin, adiponectin, non-esterified fatty acids (NEFA) and protein expression (UCP1, PepT1 and irisin) within the SM were assessed. RESULTS: Adiponectin decreased in both groups of animals fed fermented goat milk, while leptin and NEFA increased. UCP1 protein expression increased in control and anaemic animals fed fermented goat milk. UCP1 also increased in both group of anaemic animals fed either fermented cow or goat milk in comparison with their controls. Irisin increased in both group of animals fed fermented goat milk. Finally, PepT1 also showed an increased expression in control and anaemic rats fed fermented goat milk and the anaemia also induced an over-expression of this transporter in animals fed either fermented cow or goat milk. CONCLUSION: Fermented goat milk consumption during anaemia recovery diminishes adiposity depots and enhances lipolysis, increasing UCP1, PepT1 and irisin protein expression, featuring an ergogenic effect in the SM which is an important endocrine regulator of body metabolism.

Fermented goat milk improves antioxidant status and protects from oxidative damage to biomolecules during anemia recovery.

BACKGROUND: Iron deficiency anemia (IDA) is one of the most common nutritional problems in the world, and it is accepted that reactive oxygen species (ROS) production is altered during IDA. The aim of this study was to assess the influence of fermented goat and cow milks on enzymatic antioxidant activities and gene expression, and their role in protecting from oxidative damage during anemia recovery. RESULTS: After feeding the fermented milks-based diets (cow or goat), a significant elevation of some antioxidant endogenous enzymes was found, together with an increase in total antioxidant status (TAS), and a decrease in 8-hydroxy-2'-deoxyguanosine (8-OHdG) was recorded in animals consuming fermented goat milk-based diet. In contrast, DNA strand breaks, hydroperoxides, 15-F2t-isoprostanes and protein carbonyl groups were lower in some tissues in animals fed fermented goat milk-based diet, revealing an improvement in both systemic and cellular antioxidant activity of plasma and tissues due to fermented goat milk consumption. CONCLUSION: Fermented goat milk consumption induces a protective increase in TAS together with lower oxidative damage biomarkers, revealing that the milk protects main cell bioconstituents (lipids, protein, DNA, prostaglandins) from evoked oxidative damage during anemia recovery. © 2016 Society of Chemical Industry.

Omega-3 LCPUFA supplement: a nutritional strategy to prevent maternal and neonatal oxidative stress.

There is controversy about fish-oil supplementation and oxidative damage. This ambiguity should be explored to elucidate its role as modulator of oxidative stress, especially during gestation and postnatal life. This is the objective of this study. One hundred ten pregnant women were divided in two groups: control group CT (400 mL/day of the control dairy drink); supplemented group FO (400 mL/day of the fish oil-enriched dairy drink (±400-mg EPA-DHA/day)). Different biomarkers of oxidative damage were determined in the mother's at enrolment, at delivery and at 2.5 and 4 months postpartum and newborns at delivery and at 2.5 months postpartum. Omega-3 LC-PUFA supplementation during pregnancy and lactation decreased plasma hydroperoxides especially in newborn at delivery (P = 0.001) and 2.5 months (P = 0.006), increased superoxide dismutase (SOD) and catalase (CAT) in mothers at delivery (P = 0.024 (SOD)) and after 2.5 months (P = 0.040 (CAT)) and in newborns at 2.5 months (P = 0.035 (SOD); P = 0.021 (CAT)). Also, supplementation increased α-tocoferol in mothers at 2.5 months (P = 0.030) and in umbilical cord artery (P = 0.039). Higher levels of CoQ10 were found in mothers at delivery (P = 0.039) as well as in umbilical cord vein (P = 0.024) and artery (P = 0.036). Our supplementation prevents the oxidative stress in the mother and neonate during the first months of postnatal life, being a potential preventive nutritional strategy to prevent functional alterations associated with oxidative stress that have an important repercussion for the neonate development in the early postnatal life.

Gender specific differences in oxidative stress and inflammatory signaling in healthy term neonates and their mothers.

BACKGROUND: Gender is a crucial determinant of life span, but little is known about gender differences in free radical homeostasis and inflammatory signaling. The aim of the study was to determine gender-related differences concerning oxidative stress and inflammatory signaling of healthy neonates and mothers. METHODS: Fifty-six mothers with normal gestational course and spontaneous delivery were selected. Blood samples were collected from the mother (at the beginning of delivery and start of expulsive period) and from neonate (from umbilical cord vein and artery). RESULTS: The mothers of girls featured a higher total antioxidant status and lower plasma hydroperoxides than the mother of boys. Regarding the neonates, the girls featured a higher total antioxidant status and lower plasma membrane hydroperoxides in umbilical cord artery together with higher catalase, glutathione peroxidase, and superoxide dismutase activities. Lower levels of interleukin 6, tumor necrosis factor alpha, and prostaglandin E2 were observed in the mothers of girls and higher level of soluble tumor necrosis factor receptor II. In the neonates, lower levels of interleukin 6 and tumor necrosis factor alpha were observed in umbilical artery and higher soluble tumor necrosis factor receptor II in umbilical cord vein and artery of girls. CONCLUSION: An association between gender, oxidative stress, and inflammation signaling exists, leading to a renewed interest in the neonate's sex as a potential risk factor to several alterations.

Production and chemical composition of two dehydrated fermented dairy products based on cow or goat milk.

The aim of this study was to identify the differences between the main macro and micronutrients including proteins, fat, minerals and vitamins in cow and goat dehydrated fermented milks. Fermented goat milk had higher protein and lower ash content. All amino acids (except for Ala), were higher in fermented goat milk than in fermented cow milk. Except for the values of C11:0, C13:0, C16:0, C18:0, C20:5, C22:5 and the total quantity of saturated and monounsaturated fatty acids, all the other fatty acid studied were significantly different in both fermented milks. Ca, Mg, Zn, Fe, Cu and Se were higher in fermented goat milk. Fermented goat milk had lower amounts of folic acid, vitamin E and C, and higher values of vitamin A, D3, B6 and B12. The current study demonstrates the better nutritional characteristics of fermented goat milk, suggesting a potential role of this dairy product as a high nutritional value food.

Folic acid supplemented goat milk has beneficial effects on hepatic physiology, haematological status and antioxidant defence during chronic Fe repletion.

The aim of the current study was to asses the effect of goat or cow milk-based diets, either normal or Fe-overloaded and folic acid supplement on some aspects of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in liver, brain and erythrocyte of control and anaemic rats after chronic Fe repletion. 160 male Wistar rats were placed on 40 d in two groups, a control group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet. Lately, the rats were fed with goat and cow milk-based diets during 30 d, with normal-Fe content or Fe-overload and either with normal folic or folic acid supplemented. Fe-overload increased plasma alanine transaminase and aspartate transaminase levels when cow milk was supplied. Dietary folate supplementation reduced plasma transaminases levels in animals fed goat milk with chronic Fe overload. A remarkable increase in the superoxide dismutase activity was observed in the animals fed cow milk. Dietary folate supplement lead to a decrease on the activity of this enzyme in all the tissues studied with both milk-based diets. A concomitant increment in catalase was also observed. The increase in lipid peroxidation products levels in rats fed cow milk with Fe-overload, suggest an imbalance in the functioning of the enzymatic antioxidant defence. In conclusion, dietary folate-supplemented goat milk reduces both plasma transaminases levels, suggesting a hepatoprotective effect and has beneficial effects in situation of Fe-overload, improving the antioxidant enzymes activities and reducing lipid peroxidation.

Goat milk supplemented with folic acid protects cell biomolecules from oxidative stress-mediated damage after anaemia recovery in comparison with cow milk.

BACKGROUND: Fe overload is a common consequence of the anaemia treatment, increasing the oxidative stress and promoting the accumulation of damaged biomolecules, with the subsequently impairment of cell functions. Oxidative stress and the role of folic acid preventing free radical damage have been extensively studied; nevertheless, no studies are available about the influence of folic acid-supplemented goat milk consumption on the oxidative stress-mediated damage. AIM: The objective of the present study was to assess the influence of folic acid supplementation of goat milk- or cow milk-based diets, after Fe-overload treatment to palliate anaemia, on oxidative stress-mediated biomolecular damage in the liver, brain, erythrocytes, duodenal mucosa and plasma. METHODS: Control and anaemic rats were fed goat milk- or cow milk-based diets, either with normal Fe or Fe overload (450 mg/kg), and normal folic acid (2 mg/kg) or folic acid supplemented (40 mg/kg) for 30 days. RESULTS: During chronic Fe repletion, background DNA damage was significantly lower in anaemic rats fed folic acid-supplemented goat milk-based diet, as revealed by tail DNA (%), and folic acid-supplemented goat milk also had a beneficial effect, reducing the extent of lipid peroxidation in liver, plasma, erythrocytes and especially in brain and duodenal mucosa. Furthermore, protein oxidative damage was lower in anaemic rat duodenal mucosa for all goat milk-based diets. CONCLUSIONS: Folic acid supplement in goat milk avoids the undesirable effects of Fe overload during anaemia recovery in all the tissues studied, especially in the liver and duodenal mucosa, which are the tissues with higher exposition to dietary Fe.

Assessment of muscle endocrine function and inflammatory signalling in male school children following a physical activity programme.

BACKGROUND & AIMS: Regular and planned physical activity can diminish the risk of numerous illnesses. However, school children and teenagers often exercise intermittently and for brief periods, restricting potential benefits. Furthermore, previous studies mainly focused on body composition, without providing molecular mechanisms elucidating the role of physical activity in muscle tissue and inflammatory signalling. The objective of this study was to determine the effect of a vigorous physical activity intervention on endocrine muscle function and cytokine output in children. METHODS: 103 boys were divided into two groups: control (n = 51, did not perform additional physical activity) and exercise (n = 52, performed vigorous physical activity). Body composition measurements, endocrine muscle function and inflammatory signalling biomarkers were assessed at enrolment and after 6 months of intervention. RESULTS: No statistical significance was found for fractalkine, oncostatin, EGF, TNF-α and eotaxin. However, LIF, FBAP3, IL-6, FGF21 and IL-15 increased in the exercise group at the end of the protocol, though myostatin got decreased. In contrast, IFN-γ was increased in the exercise group at the beginning and end of the exercise protocol, IL-10 was also increased in this group, IL-1α decreased in the exercise group before and after the exercise protocol, and IP-10 and MCP-1 also decreased in the exercise group. CONCLUSION: It can be affirmed that a physical activity programme for boys was shown to produce changes in body composition (decreased fat mass, increased lean mass) and in markers of endocrine muscle function and cytokine release. It is possible that these changes, if sustained, could reduce the risk of chronic disease.

Implications of Prenatal Exposure to Endocrine-Disrupting Chemicals in Offspring Development: A Narrative Review.

During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum.

Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

BMPER protein is a negative regulator of hepcidin and is up-regulated in hypotransferrinemic mice.

The BMP/SMAD4 pathway has major effects on liver hepcidin levels. Bone morphogenetic protein-binding endothelial cell precursor-derived regulator (Bmper), a known regulator of BMP signaling, was found to be overexpressed at the mRNA and protein levels in liver of genetically hypotransferrinemic mice (Trf(hpx/hpx)). Soluble BMPER peptide inhibited BMP2- and BMP6-dependent hepcidin promoter activity in both HepG2 and HuH7 cells. These effects correlated with reduced cellular levels of pSMAD1/5/8. Addition of BMPER peptide to primary human hepatocytes abolished the BMP2-dependent increase in hepcidin mRNA, whereas injection of Bmper peptide into mice resulted in reduced liver hepcidin and increased serum iron levels. Thus Bmper may play an important role in suppressing hepcidin production in hypotransferrinemic mice.

Bile composition, plasma lipids and oxidative hepatic damage induced by calcium supplementation; effects of goat or cow milk consumption.

Calcium-fortified foods, especially milk and dairy products are recommended to be consumed daily for groups in risk of nutritional deficiency, including children, young adults, menopausal women, pregnant women and the elderly, however Ca-supplementation promotes gallstone formation because Ca is a nucleating factor. The objective of the current study was to assess the influence of cow or goat milk-based diets, either normal or Ca-supplemented, on bile composition, biochemical parameters and hepatic antioxidant status. Weanling male rats were randomly divided into six groups, fed standard, goat or cow milk-based diets, either with normal Ca content (5.0 g/kg), or Ca-supplemented (10.0 g/kg), for 2 weeks. Bile cholesterol concentration and output was higher in rats fed goat milk in comparison with those fed with standard and cow-milk-based diet. Ca-supplementation increased lithogenic index with the standard and cow-milk based diets, this change was not observed with the goat milk diet. Activities of plasma transaminases were also lower in the animals fed Ca-supplemented goat milk, in comparison with the other diets assayed. In general, Ca-supplement in the diet led to an increase in the hepatic oxidative damage, with an increase in the activities of all the antioxidant enzymes studied in the standard and cow milk diet, but not with goat milk. The habitual consumption of goat milk has positive effects on the plasma lipid profile, biliary composition and hepatic antioxidant defence. In addition, under our experimental conditions, Ca-supplementation of this type of milk does not increase the lithogenic index, or hepatic oxidative damage.