Effect of obesity, lipids and adipokines on allergic rhinitis risk: a Mendelian randomization study

Abstract Objectives: Observational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. Methods: Summary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: After Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765-0.990, p = 0.035; OR = 0.732, 95% CI 0.551-0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. Conclusion: The study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidence: This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

Correlation of serum FABP4 and PPAR γ levels with nonalcoholic fatty liver disease and type 2 diabetes mellitus / 中华内分泌外科杂志

Objective:To explore the correlation between serum adipocyte fatty acid binding protein 4 (FABP4) and peroxisome proliferator activated receptor gamma (PPAR gamma) levels and metabolism related fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) .Methods:230 patients with T2DM and MAFLD in Zhangjiakou First Hospital from Feb. 2019 to Feb. 2021 were selected. According to their disease conditions, 80 patients with T2DM and without MAFLD were set as simple T2DM group, 78 patients with MAFLD and normal glucose tolerance were set as simple MAFLD group, 72 patients with T2DM and MAFLD were set as T2DM and MAFLD group, and 100 healthy volunteers in the same period were selected as the control group.Results:The levels of HOMA-IR and FABP4 in T2DM patients were significantly higher than those in the control group ( P<0.05) , while the levels of HDL-C, crea and PPAR γ in T2DM grou were significantly lower than those in the control group ( P<0.05) . The levels of BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 in MAFLD group were significantly higher than those in control group ( P<0.05) , while the level of PPAR γ in MAFLD group was significantly lower than that in control group ( P<0.05) . BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 of T2DM patients with MAFLD were significantly higher than those of T2DM patients without MAFLD and control group ( P<0.05) , while HDL-C and PPAR γ were significantly lower than those of T2DM patients without MAFLD and control group ( P<0.05) . HOMA-IR and FABP4 in T2DM patients with MAFLD were significantly higher than those in MAFLD group ( P<0.05) , while HDL-C, crea and PPAR γ were significantly lower than those in MAFLD group ( P<0.05) . FABP4 was positively correlated with HOMA-IR and CREA (all P<0.05) , and negatively correlated with HDL-Cand PPAR γ (all P<0.05) . PPAR γ was positively correlated with TG and ALT (all P<0.05) , and negatively correlated with HOMA-IR ( P<0.05) . Alt, TG, HOMA-IR, FABP4 and PPAR γ were independent risk factors for MAFLD in T2DM patients ( P<0.05) . Conclusion:FABP4 is positively correlated with the occurrence of T2DM and MAFLD, PPAR γ is negatively correlated with the occurrence of T2DM and MAFLD, the negative feedback loop regulation of FABP4 and PPAR γ can cause the occurrence of insulin resistance, so as to improve the risk of T2DM combined with MAFLD, and provide clinical basis for clinical disease prevention and treatment.

Role of RNA-binding protein HuR in human adipocyte differentiation / 中华内分泌代谢杂志

Objective To investigate the expressions of RNA-binding protein human antigen R(HuR), fatty acid binding protein type 4(FABP4),fatty acid synthetase(FASN),and lipoprotein lipase(LPL)during the differentiation of human adipocytes, and to explore their possible roles. Methods Human adipose-derived mesenchymal stem cells were induced by adipogenic differentiation,and the adipogenesis of cells was observed by oil red O staining. The expressions of HuR,FABP4,FASN,and LPL mRNA and protein were detected by real-time PCR and Western blotting. After HuR was silenced by siRNA, the change of adipogenesis for human adipose-derived mesenchymal stem cells was observed and the expressions of adipogenic genes were detected. Results The expressions of HuR,FABP4,FASN,and LPL mRNA and protein were significantly increased after human adipose-derived mesenchymal stem cells were induced to differentiate into adipocytes(all P<0.01). After HuR expression was down-regulated by siRNA,the adipogenic level of human adipose-derived mesenchymal stem cells was reduced,with decreased protein levels of FABP4,FASN,and LPL(all P<0.05),which were without changes for their mRNA levels. Conclusion HuR promotes the differentiation of human adipocytes mainly via regulating the changes of FABP4,FASN,and LPL protein levels.

Relationship between serum adipocyte fatty acid binding protein and maternal complications in gestational diabetes mellitus pregnant women with satisfactory glucose control / 中国基层医药

Objective To investigate the relationship between serum adipocyte fatty acid binding protein (FABP4),insulin resistance and maternal complications in patients with gestational diabetes mellitus (GDM) with satisfactory glucose control.Methods 60 cases of pregnancy between 24 and 28 weeks of OGTT diagnosed GDM pregnant women were selected.30 cases with satisfactory blood sugar control were selected as satisfactory blood sugar control group,30 cases with unsatisfied blood sugar control were selected as unsatisfied blood glucose control group.Healthy control group was selected from 24 to 28 weeks of healthy pregnancy in 30 patients.Fasting serum FABP4,fasting blood glucose(FPG) and fasting insulin(FINS) were measured in three groups of pregnant women after 24 to 28 weeks and pregnant term.To calculate the insulin resistance index (HOMA-IR) of the steady state model,and record and observe the complications of the three groups.Results In the satisfactory blood glucose control group,the incidence rates of pregnant hypertensive disorders,excessive amniotic fluid,premature rupture of membranes,postpartum hemorrhage,cesarean section,macrosomia,neonatal asphyxia,neonatal hypoglycemia,hyperbilirubinemia of newborn were 10.0％,6.7％,13.3％,6.7％,23.3％,16.7％,10.0％,16.7％,10.0％,which were significantly lower than those in the unsatisfied blood glucose control group (23.3％,20.0％,23.3％,16.7％,33.3％,33.3％,20.0％,30.0％,36.7％),the two groups had significant differences(x2 =4.33,6.12,6.01,3.97,7.41,5.46,10.02,4.79,9.22,all P ＜ 0.05).The incidence rates of pregnant hypertensive disorders,excessive amniotic fluid,macrosomia between the satisfactory blood glucose control group (10.0％,6.7％,16.7％) and healthy control group(3.3％,0.0％,6.7％) had statistically significant differences (x2 =7.45,8.46,4.69,all P ＜ 0.05).The incidence rates of postpartum hemorrhage,premature rupture of membranes,cesarean section,neonatal asphyxia,neonatal hypoglycemia,neonatal hyperbilirubinemia between the satisfactory blood glucose control group (6.7％,13.3％,23.3％,10.0％,16.7％,10.0％) and healthy control group(10.0％,10.0％,20.0％,6.7％,13.3％,3.3％) had no statistically significant differences (all P ＞ 0.05).Pregnant 24 ～ 28 weeks,FABP4,FINS,FPG and HOMA-IR of the satisfactory blood glucose control group were (1.78 ± 0.33) ng/mL,(12.35 ± 0.48) mIU/L,(5.51 ± 0.96) rmmol/L,(3.88 ± 0.55),which of the unsatisfied blood glucose control group were (2.36 ± 0.08) ng/mL,(13.92 ± 1.17) mIU/L,(5.46 ±0.74)mmol/L,(3.95 ± 1.17),the differences between the two groups were not statistically significant (all P ＞ 0.05),and compared with the healthy control group,the differences were statistically significant(t =15.32,10.36,11.54,7.34,all P ＜ 0.05).After term pregnancy,the FINS,HOMA-IR of the satisfactory blood glucose control group were still higher than those in the healthy control group,the differences were statistically significant(all P ＜ 0.05).However,FABP4,FPG between the satisfactory blood glucose control group and healthy control group had no statistically significant differences (all P ＞ 0.05).Conclusion With the control of blood glucose levels,decreased in patients with GDM FABP4,fasting blood glucose,glycosylated hemoglobin level,but high insulin resistance still persists and glycemic control satisfaction does not completely reduced the occurrence of the complications in both mothers and neonates.

Correlations of serum adipocyte fatty acid-binding protein ,high sensitivity C reactive protein with acute ischemic stroke / 国际检验医学杂志

Objective To investigate the changes of serum adipocyte fatty acid binding protein (A-FABP) and high sensitivity C reactive protein(hs-CRP) in patients with acute ischemic stroke .Methods The total of 116 patients with acute ischemic stroke and 80 synchronously examined healthy people(controls) were collected .The levels of hs-CRP and A-FABP were detected by double-antibody sandwich enzyme linked immunosorbent assay (DAS-ELISA) in all the subjects .Stroke severity were scored by modified Rankin Scale (mRS) .The patients with acute ischemic stroke were divided into the light (mRS≤3) and the severe group(mRS>3) .Changes of the level of hs-CRP and A-FABP were compared in two groups .Linear correlation and regression analysis were per-formed to hs-CRP and A-FABP .Results The levels of serum hs-CRP and A-FABP were significantly higher in acute ischemic stroke group than those in the control group .The severer the neurologic impairment degree was in the patients with acute ischemic stroke ,the higher the levels of serum hs-CRP and A-FABP .Linear correlation and regression analysis results showed that the level of A-FABP was significantly positively correlated with the level of hs-CRP .Conclusion The levels of serum hs-CRP and A-FABP is associated with acute ischemic stroke .The level of A-FABP is significantly positively correlated with the level of hs-CRP .The hs-CRP and A-FABP may have an action in occurrence and development of acute ischemic stroke .

Recent progress in research of adipocyte fatty acid binding protein and atherosclerosis / 中华内分泌代谢杂志

Adipocyte fatty acid binding protein (AFABP) is a member of fatty acid binding protein superfamily.Studies in the relationship between AFABP and atherosclerosis may provide new ideas for its pathogenesis.This review summarised a concise and general overview of AFABP' s role in atherosclerosis and atherosclerosis-related disease.

Association of adipocyte fatty acid-binding protein with cholesterol metabolism / 中华内分泌代谢杂志

Adipocyte fatty acid-binding protein ( FABP4 ) is abundantly expressed in adipocytes and macrophages, and the physiologic function of this lipid chaperone is involved in the intracellular trafficking and targeting of fatty acids inside cell. Studies have shown that FABP4 plays a significant role in cholesterol metabolism. FABP4 can affect some key gene expression for cholesterol metabolism, thus regulate the metabolism, storage, and trafficking of cholesterol. As the development of FABP4 inhibitors, drugs targeting FABP4 are possible and can lead to a novel therapeutic strategy to prevent and treat obesity, type 2 diabetes, hypercholesterolemia, and atherosclerosis.

Association between FABP4 gene polymorphism and obesity in teenagers of Han population / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.010

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

BACKGROUND/AIMS: Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH. METHODS: Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps. RESULTS: Patients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05). CONCLUSIONS: NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Role of miR-24 in the regulation of 3T3-L1 adipicyte differentiation and the expression of fatty acid binding protein / 中国药理学通报

Aim To explore the effect of microRNAs on the differentiation of 3T3-L1 adipocytes and the expression of adipo-related gene-fatty acid binding protein during the adipocyte differentiation.Methods adipo-related microRNAs during 3T3-L1 adipocyte differentiation were screened and identified by micorRNA microarray.Constructed high-expression plasmids of the adipo-related microRNAs,were transfected into the 3T3-L1 preadipocytes by lipofectamine.While the effect of adipo-related microRNAs on the course of 3T3-L1 adipocyte differentiation was observed,the protein and mRNA expression level of fatty acid binding protein(FABP4)were analyzed by Western blot and RT-PCR during 3T3-L1 adipocyte differentiation.Results The expression profiles of microRNAs have significant changed during 3T3-L1 adipocyte differentiation,in which 35 microRNAs among them down-relation,the most lowly expression is miR-24;17 microRNAs among them up-relation,the most highly expression is miR-21.MiR-24 significantly inhibited adipocyte differentiation and maturity,while miR-21 have no significant effect.MiR-24 significantly inhibited the expression of FABP4,but had no effect on the level of its mRNA;miR-21 had no effect on the expression of protein and mRNA of FABP4.Conclusion There exist adipogenic-related microRNAs during 3T3-L1 adipocyte differentiation; miR-24 play an important role in the regulation of 3T3-L1 preadipocyte differentiation into adipocyte and the(FABP4)protein expression.

Relationship between adipocyte fatty acid-binding protein and metabolic syndrome / 中华内分泌代谢杂志

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).

Serum adipocyte-fatty acid binding protein: an important marker of abdominal obesity in adolescents / 中华内分泌代谢杂志

rs of glucose and lipid metabolism in adolescents with abdominal obesity. Determimation of serum A-FABP concentration might be useful in diagnosis and prevention of metabolic syndrome and abdominal obesity in adolescent.