Glycoalkaloid Composition and Flavonoid Content as Driving Forces of Phytotoxicity in Diploid Potato.

Despite their advantages, biotechnological and omic techniques have not been applied often to characterize phytotoxicity in depth. Here, we show the distribution of phytotoxicity and glycoalkaloid content in a diploid potato population and try to clarify the source of variability of phytotoxicity among plants whose leaf extracts have a high glycoalkaloid content against the test plant species, mustard. Six glycoalkaloids were recognized in the potato leaf extracts: solasonine, solamargine, α-solanine, α-chaconine, leptinine I, and leptine II. The glycoalkaloid profiles of the progeny of the group with high phytotoxicity differed from those of the progeny of the group with low phytotoxicity, which stimulated mustard growth. RNA sequencing analysis revealed that the upregulated flavonol synthase/flavonone 3-hydroxylase-like gene was expressed in the progeny of the low phytotoxicity group, stimulating plant growth. We concluded that the metabolic shift among potato progeny may be a source of different physiological responses in mustard. The composition of glycoalkaloids, rather than the total glycoalkaloid content itself, in potato leaf extracts, may be a driving force of phytotoxicity. We suggest that, in addition to glycoalkaloids, other metabolites may shape phytotoxicity, and we assume that these metabolites may be flavonoids.

Transcriptional and proteomic insights into phytotoxic activity of interspecific potato hybrids with low glycoalkaloid contents.

BACKGROUND: Glycoalkaloids are bioactive compounds that contribute to the defence response of plants against herbivore attack and during pathogenesis. Solanaceous plants, including cultivated and wild potato species, are sources of steroidal glycoalkaloids. Solanum plants differ in the content and composition of glycoalkaloids in organs. In wild and cultivated potato species, more than 50 steroidal glycoalkaloids were recognized. Steroidal glycoalkaloids are recognized as potential allelopathic/phytotoxic compounds that may modify the growth of target plants. There are limited data on the impact of the composition of glycoalkaloids on their phytotoxic potential. RESULTS: The presence of α-solasonine and α-solamargine in potato leaf extracts corresponded to the high phytotoxic potential of the extracts. Among the differentially expressed genes between potato leaf bulks with high and low phytotoxic potential, the most upregulated transcripts in sample of high phytotoxic potential were anthocyanin 5-aromatic acyltransferase-like and subtilisin-like protease SBT1.7-transcript variant X2. The most downregulated genes were carbonic anhydrase chloroplastic-like and miraculin-like. An analysis of differentially expressed proteins revealed that the most abundant group of proteins were those related to stress and defence, including glucan endo-1,3-beta-glucosidase acidic isoform, whose expression level was 47.96× higher in potato leaf extract with low phytotoxic. CONCLUSIONS: The phytotoxic potential of potato leaf extract possessing low glycoalkaloid content is determined by the specific composition of these compounds in leaf extract, where α-solasonine and α-solamargine may play significant roles. Differentially expressed gene and protein profiles did not correspond to the glycoalkaloid biosynthesis pathway in the expression of phytotoxic potential. We cannot exclude the possibility that the phytotoxic potential is influenced by other compounds that act antagonistically or may diminish the glycoalkaloids effect.

Leptin induces a contracting effect on guinea pig tracheal smooth muscle via the Ob-R receptor mechanism: novel evidence.

The purpose of this study was to explore the potential contracting effect of leptin on isolated guinea pig tracheal smooth muscle (TSM), the possible mechanism, and the impact of epithelium denudation or allergen sensitization, respectively. An in vitro experiment investigated the effect of leptin at a concentration of 250-1000 nmol/L on isolated guinea pig TSM with an intact or denuded epithelium. Ovalbumin and IgE were used to test the impact of active and passive sensitization. The isolated TSM strips were incubated in Krebs solution and aerated with carbogen (95% O2 and 5% CO2) via an automated tissue organ bath system (n = 4 for each group). Isometric contractions were recorded digitally using iox2 data acquisition software. The possible mechanism of leptin-induced TSM contraction was examined by preincubation with leptin receptor (Ob-R) antagonist. Leptin had significant concentration-dependent contraction effects on guinea pig TSM (p < 0.05). Epithelium denuding and active or passive sensitization significantly increased the potency of the leptin. Preincubation with a leptin receptor (Ob-R) antagonist significantly reduced the contraction effects, suggesting an Ob-R-mediated mechanism. Leptin had a contracting effect on airway smooth muscles potentiated by either epithelium denuding or sensitization, and the Ob-R mechanism was a possible effect mediator.

BCG scar, socioeconomic and nutritional status: a study of newborns in urban area of Makassar, Indonesia.

OBJECTIVE: To investigate factors that determine the response to Bacille Calmette-Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to infections or newborn's nutritional status. METHODS: The study was conducted in an urban area, in Makassar, Indonesia. At baseline, 100 mother and newborns pair from high and low SES communities were included. Intestinal protozoa, soil transmitted helminths, total IgE, anti-Hepatitis A Virus IgG and anti-Toxoplasma IgG were measured to determine exposure to infections. Information on gestational age, birth weight/height and delivery status were collected. Weight-for-length z-score, a proxy for newborns adiposity, was calculated. Leptin and adiponectin from cord sera were also measured. At 10 months of age, BCG scar size was measured from 59 infants. Statistical modelling was performed using multiple linear regression. RESULTS: Both SES and birth nutritional status shape the response towards BCG vaccination at 10 months of age. Infants born to low SES families have smaller BCG scar size compared to infants born from high SES families and total IgE contributed to the reduced scar size. On the other hand, infants born with better nutritional status were found to have bigger BCG scar size but this association was abolished by leptin levels at birth. CONCLUSION: This study provides new insights into the importance of SES and leptin levels at birth on the development of BCG scar in 10 months old infants.

OBJECTIF: Investiguer les facteurs qui déterminent la réponse à la vaccination par le BCG en milieu urbain en ce qui concerne le statut socioéconomique (SSE), l'exposition prénatale aux infections ou l'état nutritionnel du nouveau-né. MÉTHODES: L'étude a été menée dans une zone urbaine, à Makassar, en Indonésie. Au départ, 100 paires mère-nouveau-né issues de communautés à statut social élevé et faible ont été incluses. Les protozoaires intestinaux, les helminthes transmis par le sol, les IgE totales, les IgG anti-virus de l'hépatite A et anti- Toxoplasma ont été mesurés pour déterminer l'exposition aux infections. Des informations sur l'âge gestationnel, le poids/taille à la naissance et l'état d'accouchement ont été collectées. Le z-score poids-pour la taille, un indicateur indirect de l'adiposité du nouveau-né a été calculé. La leptine et l'adiponectine provenant de sérum des cordons ont également été mesurées. A l'âge de 10 mois, la taille des cicatrices de BCG a été mesurée chez 59 nourrissons. La modélisation statistique a été réalisée à l'aide d'une régression linéaire multiple. RÉSULTATS: Le statut socioéconomique et l'état nutritionnel à la naissance déterminent la réponse à la vaccination par le BCG à l'âge de 10 mois. La taille des cicatrices de BCG est plus petite chez les nourrissons nés de familles à statut socioéconomique faible comparée à celles chez ceux de familles à statut socioéconomique élevé et les IgE totales ont contribué à la réduction de la taille de ces cicatrices. En revanche, les bébés nés avec un meilleur état nutritionnel avaient une taille de cicatrice du BCG plus grande, mais cette association était supprimée par les niveaux de leptine à la naissance. CONCLUSION: Cette étude fournit de nouvelles informations sur l'importance du SSE et des niveaux de leptine à la naissance sur le développement d'une cicatrice du BCG chez des nourrissons âgés de 10 mois.

Metformin, sitagliptin, and liraglutide modulate serum retinol-binding protein-4 level and adipocytokine production in type 2 diabetes mellitus rat model.

Many adipocytokines correlate with obesity and insulin resistance. We examined the effects of metformin, sitagliptin, and liraglutide in diabetic rats. Group 1: control normal (CN) rats received oral saline daily. Group 2: diabetic non-treated (DNT) rats were injected with streptozotocin (STZ) to get diabetic then after 72 h received oral saline daily. Group 3: rats were injected with STZ then after 72 h were treated with metformin (200 mg/kg) orally. Group 4: rats were injected with STZ then after 72 h received sitagliptin 6 mg/kg orally twice daily. Group 5: rats were injected with STZ then after 72 h were treated with liraglutide at a dose of 0.3 mg/kg every 12 h subcutaneous injection. After 8 weeks, body mass, fasting blood glucose, adipocytokines, and lipid profile were assessed. From the results, we concluded that the 3 drugs improved blood glucose and insulin resistance with correction of adipocytokines serum levels; however, the liraglutide-treated group was the only group that showed significant body mass reduction.

Ursolic acid suppresses leptin-induced cell proliferation in rat vascular smooth muscle cells.

Accumulating lines of evidence indicate that high leptin levels are associated with adverse cardiovascular health in obese individuals. Proatherogenic effects of leptin include endothelial cell activation and vascular smooth muscle cell proliferation and migration. Ursolic acid (UA) has been reported to exhibit multiple biological effects including antioxidant and anti-inflammatory properties. In this study, we investigated the effect of UA on leptin-induced biological responses in rat vascular smooth muscle cells (VSMCs). A-10 VSMCs were treated with leptin in the presence or absence of UA. Intracellular reactive oxygen species (ROS) was probed by 2',7'-dichlorofluorescein diacetate. The expression of extracellular signal-regulated kinase (ERK)1/2, phospho-(ERK)1/2, nuclear factor-kappa B (NF-κB) p65 and p50, and matrix metalloproteinase-2 (MMP2) was determined by Western blotting. Immunocytochemistry and confocal laser scanning microscopy were also used for the detection of NF-κB. The secretion of MMP2 was detected by gelatin zymography. UA exhibited antioxidant activities in vitro. In rat VSMCs, UA effectively inhibited cell growth and the activity of MMP2 induced by leptin. These suppressive effects appeared by decreasing the activation of (ERK)1/2, the nuclear expression and translocation of NF-κB, and the production of ROS. UA appeared to inhibit leptin-induced atherosclerosis, which may prevent the development of obesity-induced cardiovascular diseases.

[Biological role of adipokines and their association with morbid conditions].

Adipose tissue is the source of adipokines (leptine, adiponectine, resistine, interleukin-1, 6, 7, 8, 15, visfatine, PPAR-γ, tumor necrosis factor-α, vaspine, chemerine, progranuline, endocannabinoids, lipocaline-2, apleine, omentine, nesfatine-1) - biological active molecules of adipose tissue that have local and systematic effect on body. Changing of their level in the body is associated with insulin resistance, endothelium dysfunction, arterial hypertension, bronchial asthma and obesity progressing. Adipokines are heterogenous group of molecules, one part of them is produced directly by abdominal adipose tissue; another part of them is produced in other tissues but they indirectly affect development and functioning of adipose tissue. The study of adipokines lets us observe the pathogenesis of obesity, associated cardiovascular diseases and diabetes mellitus type 2 with another way. It will give us an opportunity to compose scientific base for recognizing, preventing and treatment of such diseases. It is necessary to realize that obesity with diabetes mellitus type 2 and atherosclerosis are inflammatory diseases, that's why we need to study pro- and anti-inflammatory factors of adipokines. The production of majority of inflammatory mediators is increased in case of obesity and contributes progressing of obesity and metabolic diseases. It is actual to observe adipokines as biomarkers of pathological processes, in future it will be available to prevent pathological processes, to establish prophylaxis of disease and to support positive treatment.

[Metabolic syndrome and bipolar disorder: Is sleep the missing link?] / Syndrome métabolique et troubles bipolaires : le sommeil est-il le chaînon manquant ?

OBJECTIVE: To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP). METHOD: A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome. RESULTS: Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation. CONCLUSIONS: Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP.

Resveratrol improves high-fructose-induced vascular dysfunction in rats.

High levels of fructose in the diet results in metabolic abnormalities and vascular disorders. In this study, the effect of resveratrol (RES) on vascular relaxation and contraction responses was examined in the aorta of high-fructose (HFr)-fed rats. mRNA expressions of aortic sirtuin 1 (SIRT1), GLUT5, and aldolase B were also investigated. Rats were given fructose (30%) and (or) RES (50 mg · L(-1)) in their drinking water for 8 weeks. In the HFr-fed rats, plasma levels of arginine and the ratio of arginine:asymmetric dimethylarginine (ADMA) decreased, whereas leptin levels increased. Decreased relaxation and increased contractile responses were detected in aortic rings. However, the aortic expressions of SIRT1, GLUT5, and aldolase B remained unchanged. RES treatment restored HFr-induced vascular dysfunction without improvements in insulin resistance. Treatment of HFr-fed rats with RES increased plasma levels of arginine and the L-arginine:ADMA ratio, and decreased plasma levels of leptin. RES increased SIRT1 expression, but decreased the expression of GLUT5 and aldolase B in aortas from HFr-fed rats. These results suggest that RES contributes to the restoration of HFr-induced vascular dysfunction in rats, at least in part, by up-regulation of SIRT 1 and down-regulation of GLUT5 and aldolase B in the aorta. Moreover, RES may have a positive influence on vasculature by partly restoring the plasma arginine:ADMA ratio and leptin levels.

Leptin replacement therapy in the management of lipodystrophy syndromes.

Lipodystrophy syndromes are rare diseases of genetic or acquired origin, characterized by quantitative and qualitative defects in adipose tissue. The metabolic consequences of lipodystrophy syndromes, such as insulin resistant diabetes, hypertriglyceridemia and hepatic steatosis, are frequently very difficult to treat, resulting in significant risks of acute and/or chronic complications and of decreased quality of life. The production of leptin by lipodystrophic adipose tissue is decreased, more severely in generalized forms of lipodystrophy, where adipose tissue is absent from almost all body fat depots, than in partial forms of the disease, where lipoatrophy affects only some parts of the body and can be associated with increased body fat in other anatomical regions. Several lines of evidence in preclinical and clinical models have shown that leptin replacement therapy could improve the metabolic complications of lipodystrophy syndromes. Metreleptin, a recombinant leptin analogue, was approved as an orphan drug to treat the metabolic complications of leptin deficiency in patients with generalized lipodystrophy in the USA or with either generalized or partial lipodystrophy in Japan and Europe. In this brief review, we will discuss the benefits and limitations of this therapy, and the new expectations arising from the recent development of a therapeutic monoclonal antibody able to activate the leptin receptor.

Rare genetic causes of obesity: Diagnosis and management in clinical care.

Rare genetic forms of obesity are linked to impaired energy balance (i.e., eating behaviour and energy expenditure) involving hypothalamic pathways. More than 60 genes coding for proteins located in the hypothalamic leptin/melanocortin pathway contribute to the development of these rare forms of obesity. The ambition of the French National Protocol for the Diagnosis and Care (PNDS) of Obesity of Rare Causes was to establish practical recommendations for assessment and management at all ages. This report is available on the website of the French Health Authority (HAS). In addition to severe obesity, patients often display obesity-related comorbidities and neuropsychological/psychiatric disorders. These complex conditions make clinical management particularly challenging. Early diagnosis is critical for the organization of coordinated specialized multidisciplinary care, with mandatory interaction between caregivers, social partners and families. Strategies to prevent aggravation of obesity consist in limiting access to food, establishing a reassuring daily eating environment, and the practice of sustained adapted supervised daily physical activity. The implementation of genetic diagnosis in clinical practice now enables a personalized medicine approach with access to new drug therapies, and improves the analysis of the risk/benefit ratio of bariatric surgery.

Longitudinal changes in circulating concentrations of inflammatory markers throughout pregnancy: are there associations with diet and weight status?

The natural inflammation occurring during pregnancy can, under certain conditions, be associated with adverse pregnancy outcomes. This study aimed to (1) quantify changes in circulating concentrations of leptin, adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP) across trimesters of pregnancy, according to pre-pregnancy body mass index (ppBMI); and (2) examine the trimester-specific associations between the inflammatory markers' concentrations, a Mediterranean diet score (MDS) and the dietary inflammatory index (DII). We measured leptin, adiponectin and IL-6 by ELISA and CRP by high-sensitivity immunonephelometry, in blood samples from 79 pregnant women (age: 32.1 ± 3.7 years; ppBMI: 25.7 ± 5.8 kg/m2). Three Web-based 24-h recalls were completed at each trimester and used to compute the MDS and the DII. CRP concentrations remained stable across trimesters, whereas concentrations of leptin and IL-6 increased, and adiponectin concentrations decreased (p < 0.001). Changes in leptin and adiponectin concentrations also differed according to ppBMI categories (p < 0.05). As for the dietary scores, the only significant association was observed in the second trimester between leptin concentrations and the MDS (r = -0.26, p < 0.05). In conclusion, ppBMI and the progression of pregnancy itself probably supplant the potential associations between diet and the inflammation occurring during that period. Novelty: Circulating leptin and IL-6 concentrations increased across trimesters whereas CRP was stable, and adiponectin decreased. Variations in circulating leptin and adiponectin concentrations differed by ppBMI categories. Very few associations were observed between dietary scores and inflammatory markers.

Decreased energy availability during training overload is associated with non-functional overreaching and suppressed ovarian function in female runners.

Low energy availability (EA) suppresses many physiological processes, including ovarian function in female athletes. Low EA could also predispose athletes to develop a state of overreaching. This study compared the changes in ad libitum energy intake (EI), exercise energy expenditure (ExEE), and EA among runners completing a training overload (TO) phase. We tested the hypothesis that runners becoming overreached would show decreased EA, suppressed ovarian function and plasma leptin, compared with well-adapted (WA) runners. After 1 menstrual cycle (baseline), 16 eumenorrheic runners performed 4 weeks of TO followed by a 2-week recovery (131 ± 3% and 63 ± 6% of baseline running volume, respectively). Seven-day ExEE, EI, running performance (RUNperf) and plasma leptin concentration were assessed for each phase. Salivary estradiol concentration was measured daily. Urinary luteinizing hormone concentration tests confirmed ovulation. Nine runners adapted positively to TO (WA, ΔRUNperf: +4 ± 2%); 7 were non-functionally overreached (NFOR; ΔRUNperf: -9 ± 2%) as RUNperf remained suppressed after the recovery period. WA increased EI during TO, maintaining their baseline EA despite a large increase in ExEE (ΔEA = +1.9 ± 1.3 kcal·kg fat free mass (FFM)-1·d-1, P = 0.17). By contrast, NFOR showed no change in EI, leading to decreased EA (ΔEA = -5.6 ± 2.1 kcal·kg FFM-1·d-1, P = 0.04). Plasma leptin concentration mid-cycle and luteal salivary estradiol concentration decreased in NFOR only. Contrasting with WA, NFOR failed to maintain baseline EA during TO, resulting in poor performance outcomes and suppressed ovarian function. ClinicalTrials.gov no. NCT02224976. Novelty: Runners adapting positively to training overload (TO) increased ad libitum energy intake, maintaining baseline EA and ovarian function through TO. By contrast, NFOR runners failed to increase energy intake, showing suppressed EA and ovarian function during TO.

The effect of the artificial sweeteners on glucose metabolism in healthy adults: a randomized, double-blinded, crossover clinical trial.

This study aimed to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism. Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) that were mixed with water and standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for 2 weeks. Blood samples were collected and analyzed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin. Seventeen participants (10 females and 7 males; age, 24 ± 6.8 years; body mass index, 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared with the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared with the baseline values. These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

Serum FSH level is lower in dysovulating than in ovulating non-PCOS obese women, independently of body mass index.

OBJECTIVES: The prevalence of ovulation disorder (OD) is 3-fold higher in obese than normal-weight women. Most ODs are associated with concomitant polycystic ovary syndrome (PCOS), but obesity by itself can cause OD, through mechanisms that remain poorly documented. The literature on obese non-PCOS women with OD is sparse. The aim of the present study was to analyze a population of obese non-PCOS women with OD to shed further light on the mechanism of ovulation disorder. MATERIAL AND METHODS: This retrospective observational study of infertile obese women without PCOS compared a control group without OD (n=45) to a study group with OD (n=30) (OD group). Clinical, hormonal, and ultrasound characteristics were collected between cycle days 2 and 5. Women older than 37 years and women with PCOM (polycystic ovarian morphology) or hormonal disorder were excluded. RESULTS: Body mass index (BMI) was significantly higher in the OD group, as were waist circumference and insulin and leptin serum levels. Conversely, serum follicle stimulating hormone (FSH) levels were significantly lower. After adjustment for BMI, only serum FSH level remained significantly different between the 2 groups. Discriminant analysis suggested that FSH may have a much stronger effect on OD than BMI. CONCLUSION: Low serum FSH level may contribute to OD in some obese women, independently of BMI. The pathophysiological mechanism of this finding and its impact on therapeutic strategies must be clarified.

Leptin regulates neuropeptides associated with food intake and GnRH secretion.

The present review focused on the most important effects of leptin on the hypothalamus and on how leptin regulates neuropeptides associated with food intake and GnRH secretion. This review of the literature suggests that a reduction in leptin serum concentrations results from lower body energy reserves or poor energy availability, leading to hypothalamic secretion of neuropeptides such as NPY/AgRP and QRFP to stimulate food intake. Under these negative metabolic conditions, GnRH secretion is reduced, impairing reproductive functions. In contrast, when metabolic status is inversed by an increase in food availability, energy reserves or both, leptin serum concentrations increase to an action threshold reversing the pattern of secretion: i.e., reducing NPY/AgRP and QRFP and increasing POMC and Kisspeptin, and thereby reducing food intake and stimulating GnRH secretion to promote reproductive function.

Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats.

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey's post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

Direct inhibitory effect of flaxseed on porcine ovarian granulosa cell functions.

Flaxseed is useful as a functional food and alternative medicine owing to its beneficial health effects. Its action on ovarian cell functions and interrelationships with the upstream hormonal regulators remain unknown. Our aim was to examine the direct influence of flaxseed extract on basal porcine ovarian functions (proliferation, apoptosis), leptin release, and response to insulin-like growth factor I (IGF-I). First, we examined the effect of flaxseed extract on the accumulation of proliferation (PCNA) and apoptosis (Bax) markers and on leptin release in cultured porcine ovarian granulosa cells. Next, granulosa cells were cultured with IGF-I with and without flaxseed extract and analyzed for PCNA and Bax accumulation by quantitative immunocytochemistry and for leptin release by radioimmunoassay. Flaxseed decreased the accumulation of PCNA and increased that of Bax at all doses and reduced leptin output at 100 µg/mL. In contrast, IGF-I promoted PCNA accumulation and suppressed Bax. Flaxseed did not modify IGF-I action on these parameters. Thus, we showed that flaxseed influences porcine reproductive processes, having a direct effect on the ovary and the ability to affect ovarian cell proliferation, apoptosis, and leptin release. Furthermore, we confirmed the pro-proliferative and antiapoptotic actions of IGF-I but showed that flaxseed action on ovarian cell proliferation and apoptosis is not due to changes in the cell response to IGF-I. The potential direct anti-reproductive action of flaxseed needs to be considered during its application in nutrition, medicine, and animal production.

[Endocrine Consequences of Anorexia Nervosa]. / Endokrine Folgen der Anorexia nervosa.

Endocrine Consequences of Anorexia Nervosa Abstract. Anorexia nervosa is a perilous disease of unknown etiology that causes a variety of endocrine effects. Characteristic for anorexia nervosa are a reduced food intake and thus significant underweight, as well as the fear of gaining weight. Often sufferers also have a distorted self-perception, the urge to move and amenorrhea. AN is difficult to treat and often has a chronic course, and is associated with an increased mortality risk. The endocrinological changes occur in several endocrine axes, their extent is related to the degree of malnutrition. Low leptin levels, due to the underweight, signal a potentially dangerous lack of energy to the brain. There is a cascade of neuroendocrine adaptive responses to help the organism to survive. The effects of starvation are extensive, affecting the pituitary gland, thyroid gland, as well as the adrenal glands, gonads and bones. In positive cases, most dysfunctions are reversible; the compromised bone stability recovers only slowly.

Zinc supplementation reduces diet-induced obesity and improves insulin sensitivity in rats.

Rates of obesity have been growing at alarming rates, compromising the health of the world population. Thus, the search for interventions that address the metabolic repercussions of obesity are necessary. Here we evaluated the metabolic and antioxidant effects of zinc and branched-chain amino acids (BCAA) supplementation on obese rats. Male Wistar rats were fed either a high-fat/high-fructose diet (HFD) or a standard diet (SD) for 19 weeks. From the fifteenth week until the end of the experiment, HFD- and SD-fed rats received zinc (6 mg/kg) or BCAA (750 mg/kg) supplementation. Body weight, abdominal fat, lipid profile, blood glucose, insulin, leptin, and hepatic transaminases were evaluated. In the liver, superoxide dismutase and catalase activities and lipid peroxidation were also analyzed. HFD-fed animals showed increased weight gain, abdominal fat pad, plasma insulin, leptin, and triglycerides levels in comparison with SD-fed rats. Zinc supplementation reduced all these parameters, suggesting a beneficial role for the treatment of obesity. BCAA, on the other hand, did not show any beneficial effect. Liver antioxidant enzymes and hepatic transaminases plasma levels did not change among groups. Lipid peroxidation was higher in HFD-fed rats and was not reverted by zinc or BCAA supplementation. In conclusion, zinc supplementation may be a useful strategy for the treatment of the metabolic dysfunction associated with obesity.