Recently the prevalence of both asthma and obesity have increased substantially in many countries. The aim of this study was to evaluate the role of retinol-binding protein (RBP) 4 in childhood asthma and its association with atopy markers, pulmonary function, and bronchial hyperresponsiveness in relation to obesity. We studied 160 children between the ages 6 to 10 yr, including 122 asthmatics and 38 controls. The body mass index, pulmonary function tests, and methacholine challenge tests were measured on the same day. Total eosinophil count, serum total IgE, serum eosinophil cationic protein, and serum RBP4 were measured in all subjects. There was no difference in serum RBP4 levels between the asthmatics and the control group. In all subjects or subgroups, serum RBP4 was not associated with total eosinophil count, serum total IgE, serum eosinophil cationic protein, or PC20. There was no relationship between serum RBP4 and pulmonary function in female asthmatics. Forced expiratory volume in 1 second/forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC contributed to serum RBP4 in male asthmatics. Our findings show an association between RBP4 and pulmonary function in prepubertal male asthmatics. This relationship may indirectly affect the high prevalence of childhood asthma in males.
*Asthma/blood/immunology ; Bronchial Hyperreactivity/blood/immunology ; Bronchial Provocation Tests ; Child ; Female ; Humans ; Male ; Obesity/blood/immunology ; Retinol-Binding Proteins, Plasma/*metabolism

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-alpha. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.
Adipokines/immunology/metabolism ; Animals ; *Arthritis, Experimental/genetics/immunology/pathology ; Cell Differentiation/genetics/immunology ; *Collagen Type II/administration & dosage/immunology ; Disease Models, Animal ; Gene Expression ; Humans ; Inflammation/chemically induced/*immunology ; Interleukin-17/metabolism ; Interleukin-6/blood ; Joints/immunology/pathology ; Mice ; Mice, Inbred C57BL ; *Obesity/genetics/immunology/pathology ; *Th17 Cells/immunology/metabolism ; Tumor Necrosis Factor-alpha/blood

Objective To investigate the changes of regulatory T cells (Tregs) and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks.The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The early-stage obesity models were successfully established.Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels(P<0.05).However,there was no statistical difference in blood glucose and insulin levels between these two groups(All P>0.05). Macrophages infiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters,and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice.Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose.
Animals ; Blood Glucose ; Diet, High-Fat ; Inflammation ; Intra-Abdominal Fat ; cytology ; Leptin ; blood ; Macrophages ; cytology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity ; immunology ; T-Lymphocytes, Regulatory ; cytology

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.
Biomarkers ; blood ; Blood Glucose ; analysis ; Curcumin ; administration & dosage ; pharmacology ; therapeutic use ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; immunology ; Fatty Acid-Binding Proteins ; blood ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Obesity ; blood ; complications ; drug therapy ; immunology ; Oxidative Stress ; drug effects ; immunology ; Treatment Outcome

PURPOSE: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial. MATERIALS AND METHODS: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. RESULTS: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs. - 4.6 kg), body mass index (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group. CONCLUSION: This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.
Absorptiometry, Photon ; Adiponectin/blood ; Adult ; Anthraquinones/*therapeutic use ; Anti-Inflammatory Agents/*therapeutic use ; Appetite Depressants/therapeutic use ; C-Reactive Protein/analysis ; Cyclobutanes/*therapeutic use ; Double-Blind Method ; Female ; Humans ; Inflammation ; Lipoproteins, LDL/blood ; Male ; Obesity/*drug therapy/immunology ; Pilot Projects ; Tumor Necrosis Factor-alpha/blood ; Waist Circumference/drug effects/immunology ; Weight Loss/drug effects/*immunology

OBJECTIVETo investigate the effect of berberine on serum levels of TNF-alpha, IL-6 and adiponectin in obese mice induced by high fat diet and its potential molecular mechanisms.

METHODNormal male Kunming mice were randomly divided into two groups taking normal chow (NC, n = 10) and high fat diet (HF, n = 30), respectively. After 13 weeks, HF mice were continuously given high fat diet and divided into three groups, model group (BM), low-dosage of berberine group (BL) and high-dosage of berberine group (BH). Mice in BL and BH were administered berberine by gavage at the dosage of 50 mg x kg(-1) and 150 mg x kg(-1), respectively. Two weeks later, oral glucose tolerance test was performed. At the end of the experiment, the mice were killed and blood samples were collected. The epididymal fat tissue and liver were removed promptly and weighed. The serum cytokine was measured by ELISA. The levels of IkappaB kinase beta (IKK-beta) and IKK-beta (ser181) were detected by Western blotting.

RESULTSerum levels of TNF-alpha, IL-6 in mice of BM were significantly higher than those in NC (P < 0.05). After two-week treatment of berberine, serum levels of TNF-alpha, IL-6 in BL and BH were lower than those in BM (P < 0.05, respectively). However, there were no significant difference of adiponectin among four groups. The degrees of phosphorylation of IKK-beta (ser181) were decreased in liver and adipose tissue in BH in comparison to that in BM, although the expression of total IKK-beta did not change. Furthermore, the glucose tolerance was improved, while the body weight and epididymal fat were reduced in mice treated with berebrine. 9: Berberine is able to reduce inflammatory cytokines expression and inhibit activation of IKK-beta (ser181) in obese mice, which may partly explain the therapeutic effect of berberine on insulin resistance and abnormal glucose metabolism.

Animals ; Berberine ; administration & dosage ; Dietary Fats ; administration & dosage ; adverse effects ; Disease Models, Animal ; Glucose Tolerance Test ; Humans ; Inflammation Mediators ; blood ; Interleukin-6 ; blood ; Liver ; drug effects ; immunology ; metabolism ; Male ; Mice ; Mice, Obese ; Obesity ; blood ; drug therapy ; immunology ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; blood

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult