GFRAL Is Widely Distributed in the Brain and Peripheral Tissues of Mice.

In 2017, four independent publications described the glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as receptor for the growth differentiation factor 15 (GDF15, also MIC-1, NAG-1) with an expression exclusively in the mice brainstem area postrema (AP) and nucleus tractus solitarii (NTS) where it mediates effects of GDF15 on reduction of food intake and body weight. GDF15 is a cell stress cytokine with a widespread expression and pleiotropic effects, which both seem to be in contrast to the reported highly specialized localization of its receptor. This discrepancy prompts us to re-evaluate the expression pattern of GFRAL in the brain and peripheral tissues of mice. In this detailed immunohistochemical study, we provide evidence for a more widespread distribution of this receptor. Apart from the AP/NTS region, GFRAL-immunoreactivity was found in the prefrontal cortex, hippocampus, nucleus arcuatus and peripheral tissues including liver, small intestine, fat, kidney and muscle tissues. This widespread receptor expression, not taken into consideration so far, may explain the multiple effects of GDF-15 that are not yet assigned to GFRAL. Furthermore, our results could be relevant for the development of novel pharmacological therapies for physical and mental disorders related to body image and food intake, such as eating disorders, cachexia and obesity.

A high salt intake in early life affects stress-coping response in males but not in female rats.

Eating diets high in salt has been associated with alterations in the immune system and the potential development of neuropsychiatric disorders. This area of research shows promise, but there is currently a limited amount of research on this topic. The present study investigated whether a high salt diet (HSD) affects anhedonia and stress-coping response behaviors in young male and female Wistar rats. In this study, male and female Wistar rats were fed an HSD (8 % NaCl w/w) from weaning to post-natal day (PND) 64. From PND 60 to 64, the rats underwent a spontaneous locomotor activity test (SLA), sucrose splash test (SST), sucrose preference test (SPT), and forced swim test (FST), followed by euthanasia at PND 65. Male and female rats consuming the HSD exhibited an increase in water intake compared to the corresponding control diet (CD) groups. Male rats had lower body weight despite having similar food intakes compared to the CD group. Male rats displayed an active stress-coping behavior in the FST, characterized by increased mobility. Additionally, HSD-fed males exhibited a greater preference for sucrose solution in the SPT. However, no effect of diet and sex were detected in the SST and the SLA, and hypothalamic levels of leptin and ghrelin receptors. On the other hand, female rats were less susceptible to the experimental conditions applied in this protocol than males.

Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats.

The involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flutamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5-alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypothalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female rats.

Incidence of Urinary Infections and Behavioral Risk Factors.

This evaluation of the impact of behavioral risk factors on the incidence of urinary infections was based on a questionnaire in which 1103 respondents, predominantly women (883), participated. From the statistical processing of the data, it was observed that 598 of the respondents were of normal weight; the rest, more than half, were underweight or overweight (χ2 = 32.46, p < 0.001), with male respondents being predominantly overweight or obese (169 out of a total of 220). Most of the respondents were young (χ2 = 15.45, p < 0.001), under the age of 45 (840). According to the processed data, it was found that respondents in the age group of 26-35 years showed the greatest vulnerability to recurrent urinary infections, while the age group of 18-25 years recorded the highest number of responses related to the rare presence or even absence of episodes of urinary infections. A body weight-related vulnerability was also noted among the respondents; the majority of obese people declared that they face frequent episodes of urinary infections. Regarding diet quality, 210 respondents reported an adherence to an unhealthy diet, 620 to a moderately healthy diet, and 273 to a healthy diet. Of the respondents who adhered to a healthy diet, 223 were women (χ2 = 2.55, p = 0.279). There was a close connection between diet quality and the frequency of urinary infections: from the statistical processing of the data, it was observed that the highest percentage of respondents who rarely (57.14%) or never got urinary infections (29.30%) were among those who adhered to a healthy diet, and the highest percentage of those who declared that they often got urinary infections were among those with increased adherence to an unhealthy diet (χ2 = 13.46, p = 0.036). The results of this study highlight a strong impact of obesity, reduced consumption of fruit and vegetables, and sedentary lifestyle on the risk of recurring urinary infections.

Protection against overfeeding-induced weight gain is preserved in obesity but does not require FGF21 or MC4R.

Overfeeding triggers homeostatic compensatory mechanisms that counteract weight gain. Here, we show that both lean and diet-induced obese (DIO) male mice exhibit a potent and prolonged inhibition of voluntary food intake following overfeeding-induced weight gain. We reveal that FGF21 is dispensable for this defense against weight gain. Targeted proteomics unveiled novel circulating factors linked to overfeeding, including the protease  legumain (LGMN). Administration of recombinant LGMN lowers body weight and food intake in DIO mice. The protection against weight gain is also associated with reduced vascularization in the hypothalamus and sustained reductions in the expression of the orexigenic neuropeptide genes, Npy and Agrp, suggesting a role for hypothalamic signaling in this homeostatic recovery from overfeeding. Overfeeding of melanocortin 4 receptor (MC4R) KO mice shows that these mice can suppress voluntary food intake and counteract the enforced weight gain, although their rate of weight recovery is impaired. Collectively, these findings demonstrate that the defense against overfeeding-induced weight gain remains intact in obesity and involves mechanisms independent of both FGF21 and MC4R.

Associations between low body weight, weight loss, and medical instability in adults with eating disorders.

OBJECTIVE: The physical complications of atypical anorexia nervosa remain understudied, with most studies completed in adolescents. This study seeks to examine the impact of various weight measures as predictors of medical instability in a large cohort of adult eating disorder patients. METHODS: In this retrospective cohort study, the impact of admission body mass index (BMI), weight suppression, and recent weight loss (the rate of weight loss within the last 12 months) toward the development of medical complications of malnutrition were examined. Multivariable logistic regression assessed the association of binary clinical outcomes of interest with recent weight loss and weight suppression (adjusting for age, admission BMI, gender, and purging behaviors). Odds ratios (OR) and 99% confidence intervals were reported. RESULTS: Greater recent weight loss increased the odds of developing low prealbumin and reduced hand grip strength. A greater weight suppression was associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weekly weight gain upon nutritional rehabilitation. Lower admission BMI was predictive of all the medical outcomes examined, with the exception of bradycardia, and was generally the strongest predictor based on standardized coefficients. DISCUSSION: Recent weight loss and weight suppression are predictive of some of the physiologic changes of malnutrition, although low BMI is seemingly the greatest predictor for the development of these complications. These findings suggest that some patients with aggressive weight suppression and/or acute weight loss would benefit from medical stabilization, although this needs to be further defined. PUBLIC SIGNIFICANCE: In adults, low BMI seems to be a better predictor of medical complications than weight suppression or aggressive recent weight loss. In adults, greater weight suppression is associated with increased likelihood of amenorrhea, reduced systolic blood pressure, nadir hemoglobin, and weight gain upon nutritional rehabilitation.

Predictors of psychopathology response in atypical anorexia nervosa following inpatient treatment: A propensity score matching study of weight suppression and weight loss speed.

INTRODUCTION: This study examines weight suppression (WS) and weight loss speed (WLS) in atypical anorexia nervosa (AN) and its implications for treatment outcomes, compared to people with AN and bulimia nervosa (BN). METHOD: A mixed cross-sectional and prospective design was employed, assessing WS and WLS in people with atypical AN, AN, and BN. Participants were matched for age, gender, age of onset, and disorder duration. Clinical measurements and eating disorders questionnaire (EDE-Q) scores were employed to evaluate the response to treatment. RESULTS: Individuals with atypical individuals exhibited WS patterns similar to AN, distinct from BN. Rapid WLS predicted clinical responses in atypical AN and BN, underscoring its treatment relevance. Atypical AN showed higher eating psychopathology scores than AN or BN, emphasizing the need for a reframed diagnosis. DISCUSSION: Understanding atypical AN's connection to restrictive behaviors and weight loss informs screening, assessment, and treatment practices. Recognition of atypical AN's severity and adoption of tailored approaches are essential for recovery. This study highlights the significance of WS and WLS in atypical AN treatment outcomes, offering insights into clinical practice and care. The proposal to reframe atypical AN as a restrictive eating disorder emphasizes its clinical relevance. PUBLIC SIGNIFICANCE STATEMENT: The phenomenon of weight suppression, involving the discrepancy between past highest weight and current weight, has garnered attention due to cultural pressures emphasizing fitness and appearance. This study focuses on its implications in atypical anorexia nervosa, aiming to uncover the relationship between WS, its speed, and treatment outcomes. The investigation contributes insights into tailored interventions for atypical anorexia nervosa and enriches the understanding of this complex disorder's dynamics.

Embryonic thermal manipulation of poultry birds: Lucrative and deleterious effects.

The major efforts to improve feed conversion, increase the body weight and breast muscle yield of broilers have been focused on feeding and management at the post hatch period. However, incubation temperature is the most significant factor for the egg hatching rate, chick quality, and post hatch performance. Therefore, incubation factors affecting the performance should be taken with necessary precautions. Incubation temperature not only affects the early development of the hatchlings but also has a lasting impact on the characteristics of the chicks, such as final body weight and meat quality traits. This article provides an overview about embryonic thermal manipulation (TM) of domestic fowls and review the lucrative and deleterious effects of embryonic TM on embryo development, muscle growth, thermotolerance acquisition, and immunity.

Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats.

INTRODUCTION: Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. METHODS: Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. RESULTS: Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. CONCLUSION: Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks.

Allometric scaling of skin weight and thickness to body weight in relation to taxonomic orders and habitats in mammals.

Skin is the largest organ in a mammal body, and it exhibits most significant range of adaptations to different habitats. It is a complex, biological composite structure, consisting of epidermis, dermis and subcutaneous tissues and is used for the therapeutic application of medical devices to improve healthcare. Extensive studies have been performed on the roles of the skin; however, little is known on its physiological characteristics in relation to body size among different species. The purpose of this study was therefore to evaluate the allometric scaling of skin weight (SW) and thickness (ST) to body weight (BW) in relation to genetics and habitats. Also analysed the relationship of BW to thicknesses of epidermis, dermis and subcutaneous tissues. This study used 249 adult animals of both sexes, belonging to 144 species, clustered in 18 taxonomic orders and five types of habitats. The animals were obtained from various sources in Japan. SW and BW were weighed, and ST was measured using a calliper followed by data analysis. Results showed that SW and ST were related to BW [log SW = 0.969 × logBW - 0636, adjust. R2 : 0.975]. The BW increased with increasing skin dermal thickness (y = 0.3916x + 1.5253, adjust. R2 : 0.6921), slightly with epidermal thickness (y = 0.2495x + 0.3984, adjust. R2 : 0.3402), but not all with the thickness of subcutaneous tissues (y = 0.1454x + 2.2437, adjust. R2 : 0.0752). The ratio of SW to BW (SW/BW) distributed over a large range from 0.06 to 0.64 values and varied among animal taxonomic orders and their dwelling habitats. Close relationship of BW to SW/BW was observed in species weighing ≥200 g but not in species weighing <200 g. In conclusion, SW and ST in mammals are determined by BW. The SW/BW varies based on BW, taxonomic orders and habitat and is large in small mammals weighing ≥200 g to provide a mechanism used for survival strategy.

Chronic social defeat stress broadly inhibits gene expression in the peripheral taste system and alters taste responses in mice.

Human studies have linked stress exposure to unhealthy eating behavior. However, the mechanisms that drive stress-associated changes in eating behavior remain incompletely understood. The sense of taste plays important roles in food preference and intake. In this study, we use a chronic social defeat stress (CSDS) model in mice to address whether chronic stress impacts taste sensation and gene expression in taste buds and the gut. Our results showed that CSDS significantly elevated circulating levels of corticosterone and acylated ghrelin while lowering levels of leptin, suggesting a change in metabolic hormones that promotes food consumption. Stressed mice substantially increased their intake of food and water 3-5 days after the stress onset and gradually gained more body weight than that of controls. Moreover, CSDS significantly decreased the expression of multiple taste receptors and signaling molecules in taste buds and reduced mRNA levels of several taste progenitor/stem cell markers and regulators. Stressed mice showed significantly reduced sensitivity and response to umami and sweet taste compounds in behavioral tests. In the small intestine, the mRNA levels of Gnat3 and Tas1r2 were elevated in CSDS mice. The increased Gnat3 was mostly localized in a type of Gnat3+ and CD45+ immune cells, suggesting changes of immune cell distribution in the gut of stressed mice. Together, our study revealed broad effects of CSDS on the peripheral taste system and the gut, which may contribute to stress-associated changes in eating behavior.

Body Mass Index (BMI) Is the Strongest Predictor of Systemic Hypertension and Cardiac Mass in a Cohort of Children.

BACKGROUND: Hypertension (HTN) is a well-established cardiovascular (CV) risk factor in adults. The presence of HTN in children appears to predict its persistence into adulthood. Early diagnosis of HTN is crucial to reduce CV morbidity before the onset of organ damage. AIM: The aim of this study is to investigate cardiac damage in HTN, its risk factors (RFs), and evolution. METHODS: We conducted a prospective/retrospective study involving children referred to the Childhood Hypertension Outpatient Clinic. This study included clinical and echocardiographic assessments of cardiac morphology and function at three time points: enrollment (T0) and follow-up (T1 and T2). RESULTS: Ninety-two patients (mean age 11.4 ± 3 years) were enrolled. Cardiac eccentric and concentric hypertrophy were present in 17.9% and 9%, respectively, with remodeling in 10.5%. Overweight/obese subjects exhibited significantly higher systolic blood pressure (SBP), frequency of HTN, and body mass index (BMI) at T0 compared with patients with chronic kidney disease (CKD). SBP and BMI persisted more during follow-up. Normal-weight vs. overweight/obese patients were significantly more likely to have normal geometry. Positive correlations were found between BMI and left ventricular (LV) mass at T0, BMI and SBP at T0 and T1. Gender, BMI, SBP, and diastolic blood pressure (DBP) significantly predicted LV mass index (LVMI), but only BMI added significance to the prediction. During follow-up, the variation of BMI positively correlated with the variation of SBP, but not with LVMI. CONCLUSIONS: In our cohort, body weight is strongly associated with HTN and cardiac mass. Importantly, the variation in body weight has a more significant impact on the consensual variation of cardiac mass than blood pressure (BP) values. A strict intervention on weight control through diet and a healthy lifestyle from early ages might reduce the burden of CV morbidity in later years.

Continuous deep brain stimulation of the nucleus accumbens reduces food intake but does not affect body weight in mice fed a high-fat diet.

Obesity is an enormous health problem, and many patients do not respond to any of the available therapies. Deep brain stimulation (DBS) is currently investigated as a potential treatment for morbid obesity. In this study, we tested the hypothesis that high-frequency DBS targeting the nucleus accumbens (NAc) shell region reduces food intake and weight gain in mice fed a high-fat diet. We implanted male C57BL/6J mice with bilateral electrodes and a head-mounted microstimulator enabling continuous stimulation for up to 5 weeks. In successfully operated animals (n = 9 per group, high-frequency vs. sham stimulation), we investigated immediate and long-term stimulation effects on metabolic and behavioral phenotypes. Here we show that stimulation acutely induced a transient reduction in energy expenditure and locomotor activity but did not significantly affect spontaneous food intake, social interaction, anxiety or exploratory behaviors. In contrast, continuous stimulation over 5 weeks led to a decrease in food intake and thigmotaxis (the tendency to stay near walls in an open lit arena). However, chronic stimulation did not substantially change weight gain in mice fed a high-fat diet. Our results do not support the use of continuous high-frequency NAc shell DBS as a treatment for obesity. However, DBS can alter obesity-related parameters with differing short and long-term effects. Therefore, future research should employ time and context-sensitive experimental designs to assess the potential of DBS for clinical translation in this area.

Effects of Treadmill Running at Different Light Cycles in Mice with Metabolic Disorders.

Type 2 diabetes mellitus accounts for about 90% of cases of diabetes and is considered one of the most important problems of our time. Despite a significant number of studies on glucose metabolism, the molecular mechanisms of its regulation in health and disease remain insufficiently studied. That is why non-drug treatment of metabolic disorders is of great relevance, including physical activity. Metabolic changes under the influence of physical activity are very complex and are still difficult to understand. This study aims to deepen the understanding of the effect of physical exercise on metabolic changes in mice with diabetes mellitus. We studied the effect of forced treadmill running on body weight and metabolic parameters in mice with metabolic disorders. We developed a high-fat-diet-induced diabetic model of metabolic disorders. We exposed mice to forced treadmill running for 4 weeks. We determined glucose and insulin levels in the blood plasma biochemically and analyzed Glut-4 and citrate synthase in M. gastrocnemius muscle tissue using Western blotting. The research results show that daily treadmill running has different effects on different age groups of mice with metabolic disorders. In young-age animals, forced running has a more pronounced effect on body weight. At week 12, young obese mice had a 17% decrease in body weight. Body weight did not change in old mice. Moreover, at weeks 14 and 16, the decrease in body weight was more significant in the young mice (by 17%) compared to the old mice (by 6%) (p < 0.05). In older animals, it influences the rate of glucose uptake. At 60 min, the blood glucose in the exercised older mice decreased to 14.46 mmol/L, while the glucose concentration in the non-exercised group remained at 17 mmol/L. By 120 min, in mice subjected to exercise, the blood glucose approached the initial value (6.92 mmol/L) and amounted to 8.35 mmol/L. In the non-exercised group, this difference was 45%. The effects of physical activity depend on the time of day. The greater effect is observed when performing shift training or exercise during the time when animals are passive (light phase). In young mice, light phase training had a significant effect on increasing the content of Glut-4 in muscle tissue (84.3 ± 11.3%, p < 0.05 with control group-59.3 ± 7.8%). In aged mice, shift training caused an increase in the level of Glut-4 in muscle tissue (71.3 ± 4.1%, p < 0.05 with control group-56.4 ± 10,9%). In the group of aged mice, a lower CS level was noticed in all groups in comparison with young mice. It should also be noted that we observed that CS increased during exercise in the group of young mice, especially during light phase training. The CS content in the light phase subgroup (135.8 ± 7.0%) was higher than in the dark phase subgroup (113.3 ± 7.7%) (p = 0.0006). The CS decreased in aged chow-fed mice and increased in the high-fat-fed group. The CS content in the chow diet group (58.2 ± 5.0%) was 38% lower than in the HFD group (94.9 ± 8.8%).

Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract.

We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat ("the gravitostat") that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing ∼15% (Load) or ∼2.5% (Control) of body weight. At 3-5 days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.

Effects of 12 Weeks of Family and Individual Multi-Disciplinary Intervention in Overweight and Obese Adolescents under Cardiometabolic Risk Parameters: A Clinical Trial.

Adolescence is a complex period of human development in which young people are susceptible to unhealthy behaviors, such as physical inactivity and an unbalanced diet. This study aimed to analyze the effects of 12 weeks of multi-disciplinary family and individual intervention on cardiometabolic risk parameters in overweight and obese adolescents and compare sub-groups, considering possible differences between sexes (males vs. females vs. intervention approach). Forty-three adolescents (13.73 ± 2.46 years old) of both sexes were divided into two groups: family group (FG) (n = 21; 14.24 ± 2.61 years old) and individual group (IG) (n = 22; 13.23 ± 2.27 years old). The following parameters were evaluated: anthropometry (body weight, height, waist circumference (WC), hip circumference (HC), abdominal circumference (AC), calculation of body mass index (BMI), and waist-hip ratio (WHR)), body composition (fat mass (FM), lean mass (LM), fat-free mass (FFM), skeletal muscle mass (SMM), body fat percentage (BF), and visceral fat), biochemical measures (fasting glucose, triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL-c), and high-density lipoproteins (HDL-c)), and the measurement of systolic and diastolic blood pressure (SBP and DBP) before and after the interventions. The multi-disciplinary interventions occurred for 12 weeks (three days a week lasting 1 h and 30 min, in which 30 min were dedicated to theoretical interventions (nutrition: nutritional education and psychology: psychoeducation) and 1 h to physical exercises. A time effect was observed for LM, FFM, SMM, FM, and HDL-c, with higher values after intervention and a significant decrease for FM, BF, visceral fat, fasting glucose, TG, TC, LDL-c, and DBP (p < 0.05). However, no group, sub-group, or interaction effects were observed when comparing FG, IG, or sexes (p > 0.05). The responses of the present study show that both multi-disciplinary approaches (family and individual) promoted improvement in the body composition indicators, biochemical markers, and DBP of overweight and obese adolescents independently of the intervention group. Given this finding, health professionals, families, and adolescents could choose the type of intervention based on their preferences.

Prenatal caloric restriction adjusts the energy homeostasis and behavior in response to acute and chronic variations in food availability in adulthood.

Fetal metabolic programming produced by unfavorable prenatal nutritional conditions leads to the development of a disorder called "thrifty phenotype", which is associated with pathologies such as diabetes and obesity in adulthood. However, from an ecophysiological approach, few studies have addressed the development of thrifty phenotypes in terms of energy. This might represent an adaptive advantage against caloric deficiency conditions extending into adulthood. The objective of this study is to investigate the potential adaptive value of the thrifty phenotype expression through prenatal programming in a rodent model experiencing varying dietary conditions in different temporal contexts. To fill this gap, adult males of Mus musculus (BALB/C) from two maternal pregnancy groups were analyzed: control (ad libitum feeding) and caloric restriction from day 10 of gestation (70% restriction). Adult offspring of these groups were split further for two experiments: acute food deprivation and chronic caloric restriction at 60%. The acute food deprivation was performed for 24, 48 or 72 h while the caloric restriction regime was sustained for 20 days. For each experiment, morphological variables, such as body and organ mass, and gene expression related to lipid and carbohydrate metabolism from the liver and brain, were evaluated. In chronic caloric restriction, behavioral tests (open-field test and home-cage behavior) were performed. Our results indicate that under acute deprivation, the liver mass and triglyceride content remained unchanged in individuals subjected to prenatal restriction, in contrast to the reduction experienced by the control group. The latter is associated with the expression of the key genes involved in energy homeostasis (Pepck, Pparα/Pparγ), indicating a differential use of nutritional resources. In addition, thrifty animals, subjected to chronic caloric restriction, showed a severe reduction in locomotor and gluconeogenic activity, which is consistent with the regulatory role of Sirt1 and its downstream targets Mao and Pepck. Our results reveal that prenatal caloric restriction translates into a sparing metabolism in response to acute and chronic lack of food in adulthood.

Selective reduction of visceral adipose tissue with injectable ice slurry.

Reduction in visceral adipose tissue (VAT) mass reduces body weight and metabolic disease risk in obese patients. However surgical removal of VAT is highly invasive and thus not clinically feasible. We developed an injectable ice slurry for selective reduction of adipose tissue through cryolipolysis. The aim of this study was to investigate safety, feasibility and mechanism of ice slurry-induced cryolipolysis of VAT. Perigonadal VAT in diet-induced obese mice and rats was subjected to slurry or sham treatment. Body weight and blood chemistry were monitored for 56 days post-treatment. Histological analysis and molecular studies were performed to elucidate mechanisms of fat reduction. Treatment of VAT was well tolerated in all animals. Slurry induced adipocyte cell death via selective cryolipolysis; significant weight loss was noted at day 21 post-treatment. RNA sequencing from treated VAT samples showed increased expression of genes involved in inflammation, immune response, collagen biosynthesis and wound healing, and decreased expression of adipokines. This study demonstrates that slurry treatment is safe and effective in inducing cryolipolysis of VAT and subsequent weight loss in mice. Ice slurry is promising as a minimally-invasive treatment to reduce visceral adipose tissue.

l-Glutamine supplementation reduces gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.

l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1-3) and reduced (P2; wk 4-8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.