Short communication: Serum levels of brain-derived neurotrophic factor and association with pro-inflammatory cytokines in acute and recovered anorexia nervosa.

Brain-derived neurotrophic factor (BDNF) is a neuroprotective molecule known to be involved in neuroplasticity, learning and memory. Additionally, it may mitigate the effects of inflammation on the brain. There is inconclusive evidence as to whether reductions in BDNF found in AN are related to features associated with the illness such as changes in inflammatory markers and comorbidities, and whether they persist after recovery. This cross-sectional study measured BDNF and 36 inflammatory markers in the serum of individuals recovered from AN (rec-AN; n = 24), with acute AN (n = 56), and healthy controls (n = 51). We (a) compared BDNF concentrations between AN, rec-AN and controls including four pre-determined covariates; (b) assessed the relationship between BDNF and body mass index, eating disorder (ED) psychopathology and depression; and (c) correlated BDNF with inflammatory markers, stratified by group. The AN group showed reductions in BDNF compared to controls and rec-AN. BDNF was negatively associated with depression and ED psychopathology in the whole sample, but not the AN sample. BDNF was positively correlated with three inflammatory markers in the control group (interleukin (IL)-8, Eotaxin-3, tumor necrosis factor (TNF)-α) and negatively correlated with one (IL-16). The only pro-inflammatory marker associated with BDNF in the AN group was TNF-α, and no pro-inflammatory markers were associated with BDNF in the rec-AN group. These results indicate that BDNF serum concentrations may be a state marker of AN. In people with acute AN, BDNF levels seem to be linked to TNF-α signalling. However, BDNF concentrations do not appear to reflect AN symptom severity.

Expression of immune-related proteins and their association with neuropeptides in adolescent patients with anorexia nervosa.

Anorexia nervosa (AN) is a metabo-psychiatric disorder where alterations of cytokines, neuropeptides, neurotransmitters, and the interactions between these factors can play an important role. Thus, the primary goal of the presented study was a cross-sectional analysis of immune-related proteins in patients with AN. Moreover, the correlations between these molecules and selected neuropeptides were studied. Twenty-five adolescent inpatients girls in the acute stage of a restrictive type of AN were enrolled in the study within the first year of the disease. Additionally, thirty similar in age and height controls (CG) were also assessed. The levels of 24 immune-related proteins, including cytokines, chemokines, and proteases, were measured. Moreover, selected adipocytokines, gastrointestinal hormones, and centrally produced neuropeptides levels were determined. Finally, the correlations between these molecules were analyzed. The fasting levels of CXCL1, CXCL9, FGF2, GrB, IL1, IL6, IL8, MMP8, MMP9, CTSS were statistically lower in AN than in the CG. The concentrations of many immune-related proteins remain unchanged despite their metabolic and mental condition. Moreover, significant correlations were found between leptin and CXCL1, CXCL9, GrB, IL1, IL6, and MMP8. Leptin receptors were correlated with GrB, while resistin was associated with MMP9. Our findings suggest that the initial stage of restrictive AN among adolescents within the first year of the disease is not connected with a pro-inflammatory state. Some immune-related protein changes may be associated with altered neuropeptides, primarily leptin, its receptors, and resistin. Future research should clarify which changes are primary and secondary to weight loss and whether these changes normalize with increasing weight. This would aid in understanding the complex etiopathogenesis of AN and in the search for new methods of treatment.

Exploring the Mechanisms of Recovery in Anorexia Nervosa through a Translational Approach: From Original Ecological Measurements in Human to Brain Tissue Analyses in Mice.

Anorexia nervosa (AN) is a severe eating disorder where caloric restriction, excessive physical activity and metabolic alterations lead to life-threatening situations. Despite weight restoration after treatment, a significant part of patients experience relapses. In this translational study, we combined clinical and preclinical approaches. We describe preliminary data about the effect of weight gain on the symptomatology of patients suffering from acute AN (n = 225) and partially recovered (n = 41). We measured more precisely physical activity with continuous cardiac monitoring in a sub-group (n = 68). Using a mouse model, we investigated whether a long-term food restriction followed by nutritional recovery associated or not with physical activity may differentially impact peripheral and central homeostatic regulation. We assessed the plasma concentration of acyl ghrelin, desacyl ghrelin and leptin and the mRNA expression of hypothalamic neuropeptides and their receptors. Our data show an effect of undernutrition history on the level of physical activity in AN. The preclinical model supports an important role of physical activity in the recovery process and points out the leptin system as one factor that can drive a reliable restoration of metabolic variables through the hypothalamic regulation of neuropeptides involved in feeding behavior.

Vitamin D Level Trajectories of Adolescent Patients with Anorexia Nervosa at Inpatient Admission, during Treatment, and at One Year Follow Up: Association with Depressive Symptoms.

(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. MATERIAL AND METHODS: The study covered 472 girls (age: 11-19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = -0.46; p < 0.0001) and BMI (r = -0.67; p < 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p < 0.0001, respectively). CONCLUSIONS: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC). METHODS: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal. RESULTS: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037). CONCLUSIONS: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.

Neuropeptide Y and Peptide YY in Association with Depressive Symptoms and Eating Behaviours in Adolescents across the Weight Spectrum: From Anorexia Nervosa to Obesity.

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.

CONTEXT: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN: Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.

Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.

Fractalkine, sICAM-1 and Kynurenine Pathway in Restrictive Anorexia Nervosa-Exploratory Study.

The link between the kynurenine pathway and immunomodulatory molecules-fractalkine and soluble intercellular adhesion molecule-1 (sICAM-1)-in anorexia nervosa (AN) remains unknown. Fractalkine, sICAM-1, tryptophan (TRP), kynurenine (KYN), neuroprotective kynurenic acid (KYNA), neurotoxic 3-OH-kynurenine (3-OH-KYN), and the expression of mRNA for kynurenine aminotransferases (KAT1-3) were studied in 20 female patients with restrictive AN (mostly drug-free, all during first episode of the disease) and in 24 controls. In AN, serum fractalkine, but not sICAM-1, KYNA, KYN, TRP or 3-OH-KYN, was higher; ratios TRP/KYN, KYN/KYNA, KYN/3-OH-KYN and KYNA/3-OH-KYN were unaltered. The expression of the gene encoding KAT3, but not of genes encoding KAT1 and KAT2 (measured in blood mononuclear cells), was higher in patients with AN. In AN, fractalkine positively correlated with TRP, while sICAM-1 was negatively associated with 3-OH-KYN and positively linked with the ratio KYN/3-OH-KYN. Furthermore, TRP and fractalkine were negatively associated with the body mass index (BMI) in AN. Expression of KAT1, KAT2 and KAT3 did not correlate with fractalkine, sICAM-1 or BMI, either in AN or control. Increased fractalkine may be an independent factor associated with the restrictive type of AN. Excessive physical activity probably underlies increased expression of KAT3 observed among enrolled patients. Further, longitudinal studies on a larger cohort of patients should be aimed to clarify the contribution of fractalkine and KAT3 to the pathogenesis of AN.

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

The influence of homeostatic mechanisms on neural regulation of food craving in anorexia nervosa.

BACKGROUND: Restrictive food intake in anorexia nervosa (AN) has been related to an overactive cognitive control network inhibiting intuitive motivational responses to food stimuli. However, the influence of short-term homeostatic signaling on the neural regulation of cue-induced food craving in AN is still unclear. METHODS: Twenty-five women with AN and 25 matched normal-weight women were examined on two occasions after receiving either glucose or water directly into their stomach using a nasogastric tube. Participants were blinded to the type of infusion. An event-related functional magnetic resonance imaging paradigm was used to investigate the effect of intestinal glucose load on neural processing during either simple viewing or distraction from food stimuli. RESULTS: Neural differences between patients with AN and normal-weight participants were found during the distraction from food stimuli, but not during the viewing condition. When compared to controls, patients with AN displayed increased activation during food distraction in the left parietal lobule/precuneus and fusiform gyrus after water infusion and decreased activation in ventromedial prefrontal and cingulate regions after intestinal glucose load. CONCLUSIONS: Independent of the cephalic phase and the awareness of caloric intake, homeostatic influences trigger disorder-specific reactions in AN. Food distraction in patients with AN is associated with either excessive higher-order cognitive control during physiological hunger or decreased internally directed attention after intestinal glucose load. These findings suggest that food distraction plays an important role in the psychopathology of AN. This study was registered on clinicaltrials.gov with identifier: NCT03075371.

Blood SIRT1 Shows a Coherent Association with Leptin and Adiponectin in Relation to the Degree and Distribution of Adiposity: A Study in Obesity, Normal Weight and Anorexia Nervosa.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

Anorexia nervosa manifesting as massive ascites, hypercholesterolemia, and sequential binge eating in an 11-year-old girl: A case report.

RATIONALE: Anorexia nervosa (AN) is a serious eating disorder associated with a distorted body image. Hypercholesterolemia has been found in patients with AN but the mechanism of hyperlipidemia in AN remains little known. Ascites in patients with AN has been attributed to hypoalbuminemia and liver diseases, but massive ascites without the aforementioned etiologies has never been reported in AN. PATIENT CONCERNS: An 11-year-old girl was admitted for exclusion of organic underlying diseases due to severe body weight loss (18% within 3 weeks), poor appetite, and hypercholesterolemia (274 mg/dL). She complained of heartburn sensation, nausea, vomiting, constipation, and postprandial dull abdominal pain with fullness. DIAGNOSES: The patient's condition met with all 3 of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for diagnosing AN. On admission, her total cholesterol level was 337 mg/dL and hypocomplementemia (C3 55.5 mg/dL) was also found. Abdominal sonography and computed tomography scans showed massive ascites. However, neither proteinuria nor hypoalbuminemia was found. Upper gastroduodenal endoscopy showed chronic superficial gastritis and colonoscopy revealed negative findings. Ascites obtained by paracentesis demonstrated a transudate without bacterial infection, tuberculosis, or pancreatitis. Exploratory laparoscopy showed nonpurulent ascites. However, biopsies from the small intestine, mesentery, and liver showed chronic inflammation and fibrosis. INTERVENTIONS: The intensive nutritional therapy by increasing total energy intake stepwise with a combination of high-energy formula and her favorite foods. OUTCOMES: Her hypercholesterolemia, hypocomplementemia, and massive ascites resolved after her weight was restored. She developed binge eating with continuous weight gain after discharge. Her weight significantly increased to an obese level (body mass index [BMI] 25.9 kg/m) after loss to follow-up for 4 years until she returned to our emergency room due to suicide attempt. CONCLUSION: Diagnostic crossover between subtypes in anorexia nervosa might be a potential risk factor for illness severity and poor prognosis. AN can manifest as massive ascites with normal albumin concentrations that could possibly be due to chronic inflammation of the intestinal serosa, mesentery, and peritoneal surface of the liver.

Backstage of Eating Disorder-About the Biological Mechanisms behind the Symptoms of Anorexia Nervosa.

Anorexia nervosa (AN) represents a disorder with the highest mortality rate among all psychiatric diseases, yet our understanding of its pathophysiological components continues to be fragmentary. This article reviews the current concepts regarding AN pathomechanisms that focus on the main biological aspects involving central and peripheral neurohormonal pathways, endocrine function, as well as the microbiome-gut-brain axis. It emerged from the unique complexity of constantly accumulating new discoveries, which hamper the ability to look at the disease in a more comprehensive way. The emphasis is placed on the mechanisms underlying the main symptoms and potential new directions that require further investigation in clinical settings.

Zinc Deficiency as a Reversible Cause of Heart Failure.

Zinc, an essential micronutrient, affects the heart by modulating cardiomyocyte oxidative stress and maintaining myocardial structure, among other mechanisms. In cross-sectional studies, patients with heart failure have often had zinc deficiencies, suggesting effects on the ongoing pathogenesis of heart failure. Low plasma and myocardial zinc levels may cause reversible cardiomyopathy in patients who have nutritional deficiencies. We present the case of a 24-year-old woman with anorexia nervosa and new-onset heart failure whose depressed left ventricular systolic function improved after zinc supplementation. To our knowledge, this is the first report of low plasma zinc levels as the chief cause of cardiomyopathy that resolved after zinc supplementation.