BACKGROUND With the expanding understanding of conditions contributing to heightened cardiovascular risk, emerging pathologies like nonalcoholic fatty liver disease (NAFLD) and polycystic ovary ...syndrome (PCOS) are being recognized as hepatic and ovarian manifestations of metabolic syndrome, respectively. This study aims to elucidate the recent advancements in our comprehension of the link between these conditions in the pediatric demographic, focusing on pathogenesis, incidence, diagnostic methods, and effective therapeutic strategies. MATERIAL AND METHODS A systematic review was conducted following the PRISMA 2020 guidelines, with a search of the PubMed database for eligible studies published in the ten years leading up to January 2023. RESULTS Out of 23 reports based on 16 original studies, we found a significantly higher prevalence of NAFLD in adolescents with PCOS compared to healthy controls. Factors such as increased de novo lipogenesis, alterations in gut microbiota, and a deficiency in growth differentiation factor-15 have been implicated in their pathogenesis. Additionally, novel biomarker S100A4, a clinical prediction score for hepatic steatosis in PCOS, and pharmacotherapy involving low-dose spironolactone, pioglitazone, and metformin have been proposed to enhance the management of these conditions. CONCLUSIONS A meticulous approach to the prevention, detection, and treatment of NAFLD in adolescents with PCOS is paramount to mitigate further complications. The study underlines the need for ongoing research to refine our understanding and management of these interconnected metabolic disorders.
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver pathology worldwide due to the rising prevalence of obesity. This term includes changes from simple steatosis to ...steatohepatitis and fibrosis. It was previously thought to be a hepatic manifestation of metabolic syndrome, but recent literature describes this relation as much more complex and bi-directional. Development of NAFLD is associated with other metabolic syndrome components but it can also exacerbate insulin resistance and increase cardiovascular risk. Recently a lot of attention is brought to the role of lipids and lipotoxicity in pathogenesis and progression of non-alcoholic fatty disease. It seems that some lipid classes can be protective against liver injury while others are harmful in excessive amounts. This study presents an overview of the main lipids involved in the pathogenesis of non-alcoholic fatty liver disease and summarizes their association with lipotoxicity, insulin resistance, oxidative stress and other processes responsible for its progression.
Hepatokines and non-alcoholic fatty liver disease Lebensztejn, Dariusz M; Flisiak-Jackiewicz, Marta; Białokoz-Kalinowska, Irena ...
Acta biochimica Polonica,
01/2016, Letnik:
63, Številka:
3
Journal Article
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Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to ...steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone-binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver-derived proteins with the development and progression of NAFLD.
Introduction Seasonal allergic rhinitis (SAR) and bronchial asthma are typical manifestations of pollen-food sensitization in adults. There is limited information regarding the sensitization patterns ...of pollen-food allergy in children. Aim: To evaluate the prevalence of SAR in children with pollen-food sensitization and assess the impact of food allergens on nasal symptoms. Material and methods Forty-three children with pollen-food sensitization aged 2–14 years were evaluated for evidence of SAR. The inclusion criteria was IgE-mediated sensitization to pollen and homologous food allergens. The control group consisted of 19 children with SAR caused by pollen without sensitization to homologous food allergens. Results Allergic rhinitis was the main symptom in 65.1% of children; in 25.6% an association between ingestion of pollen-related foods and nasal symptoms was observed. The simultaneous sensitization to animal origin food allergens was stated in 63.3% of children with SAR. In 25.6% anaphylactic reactions to foods were registered. 37.2% of children were asymptomatic to pollen origin foods despite pollen-food sensitization. The statistically significant differences between values were noticed in comparison to the control group. Conclusions Allergic rhinitis is a common manifestation of pollen-food sensitization in children and this type of immunological hyperreactivity should be taken into account regardless of age. The lack of association of symptoms with plant origin foods in the majority of cases and the asymptomatic course of food sensitization in more than one third of patients indicates the need for follow-up and being careful in routine recommending the avoidance diet.
Celiac disease (CD) is an autoimmune disorder of the small intestine caused by an abnormal immune response to gluten proteins and is often characterized by gastrointestinal symptoms. Food allergy ...(FA) is an adverse immune sensitivity to ingested food proteins leading to inflammation in various organs including the gastrointestinal tract. The relationship between CD and FA remains unclear. This study aimed to assess the prevalence and clinical relevance of immunoglobulin E (IgE)-mediated food sensitization in children with CD.
Fifty-nine children diagnosed with CD were reviewed for clinical symptoms and evidence of IgE-sensitization to food and airborne allergens using the PolyCheck method.
IgE-mediated sensitization has been diagnosed in 20.3% of children with CD (CD/ A). In the CD/A group, 58.3% of children were sensitized to food and 66.7% to airborne allergens. Further, 41.7% of patients with CD and allergy reported gastrointestinal tract symptoms associated with the ingestion of sensitizing foods. Analysis of the clinical status revealed that the incidence of other allergic disorders in the CD/A group was as follows: atopic dermatitis (33.3%), asthma (25.0%), and allergic rhinitis (16.7%). The percentage of eosinophils was significantly higher in the CD/A group than in the CD group (0.33±0.25 vs. 0.11±0.09;
=0.006).
The diagnosis of CD does not exclude FA. The gastrointestinal symptoms in children with CD may be the result of both CD and FA; therefore, children with CD should be evaluated for the presence of FA regardless of age.
•Higher total fatty acid concentrations were observed in obese children and patients with nonalcoholic fatty liver disease.•Selected fatty acids included myristic, palmitic, palmitoleic, stearic, ...oleic, linoleic, arachidic, behenic, and nervonic.•Total fatty acid concentration is positively correlated with parameters of insulin resistance.
It has been suggested that circulating fatty acids (FAs) take part in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in children with obesity. The aims of this study were to evaluate the serum FA concentration in this pediatric population.
The prospective study included 80 children with obesity and suspected liver disease. Patients with viral hepatitis, autoimmune, toxic, and selected metabolic liver diseases were excluded. Criteria for NAFLD diagnosis included liver steatosis in ultrasound as well as elevated alanine transaminase (ALT) serum activity. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). Fasting serum FA concentrations were measured in all children using gas-liquid chromatography.
NAFLD was diagnosed in 31 children. Total FA concentration was significantly higher (P < 0.01) in all obese children as well as in obese children with NAFLD compared with controls. In children with NAFLD, a significant, positive correlation was found between total FA concentration and cholesterol (R = 0.47, P < 0.01), triacylglycerols (R = 0.78, P < 0.001), and insulin (R = 0.45, P < 0.011). In a group of children with obesity, TILC correlated positively with saturated FA concentration (R = 0.23, P < 0.05).
Data from the present study do support the hypothesis that FAs are potentially involved in the pathogenesis of NAFLD in children with obesity.
Objective To evaluate the efficacy and safety of omega-3 fatty acid supplementation in children with nonalcoholic fatty liver disease (NAFLD). Study design Overweight/obese children with NAFLD ...(n = 76; median age, 13 years; IQR, 11.1-15.2 years) were eligible to participate in the study. The diagnosis of NAFLD was based on elevated alanine aminotransferase (ALT) to ≥30% of the upper limit of normal (ULN) and liver hyperechogenicity on ultrasound. Patients were randomized to receive omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid, 450-1300 mg/day) or placebo (omega-6 sunflower oil). The primary outcome was the number of patients who demonstrated decreased ALT activity by ≥0.3 times the ULN. Secondary outcomes included alterations in liver function tests, liver hyperechogenicity, insulin resistance, and other metabolic markers after 6 months of intervention. Results Out of 76 enrolled patients, 64 completed the trial and were analyzed. After 6 months, we found no significant differences between the omega-3 and placebo groups in the number of patients with decreased ALT by ≥0.3 times the ULN (24 vs 23) or in median (IQR) ALT activity (48.5 31-62 U/L vs 39 27-55 U/L), liver hyperechogenicity, insulin resistance, or serum lipid levels. However, patients in the omega-3 group had lower levels of aspartate aminotransferase (28 25-36 U/L vs 39 27-55 U/L; P = .04) and gamma-glutamyl transpeptidase (26 17.5-36.5 U/L vs 35 22-52 U/L; P = .04), and significantly higher levels of adiponectin. Conclusion Omega-3 fatty acid supplementation did not increase the number of patients with decreased ALT levels and it did not affect liver steatosis on ultrasound, but it improved aspartate aminotransferase and gamma-glutamyl transpeptidase levels in children with NAFLD compared with placebo. Trial registration Registered with ClinicalTrials.gov : NCT01547910.
Hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). ...Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD.
The prospective study included 80 obese children (aged 7-17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson's disease, alfa-1-antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (
HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children.
NAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in
HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2-3).
Elevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ulcerative colitis (UC) and Crohn's disease (CD) represent inflammatory bowel diseases (IBD) with multifactorial pathogenesis, involving genetic, environmental and microbial factors. Interactions ...between gut microbiota and immune system result in changes in metabolic pathways. Metabolomics is a comprehensive and quantitative (or semi-quantitative) analysis of metabolites synthetized in human's biological system. It has been shown that metabolic profiling might be used to identify disease biomarkers. Recent findings confirmed alterations in the number of metabolites in patients with IBD. However, most of the studies included adult individuals with ongoing treatment which might have affected the metabolite profiling. Therefore, the aim of our study was to collect the knowledge about metabolomics in paediatric patients with CD or UC based on the currently published literature.
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