Correlation Between IP6K1 And Adiponectin In Overweight/obese Population And 3T3L1 Cells And Its Mechanism

Research BackgroundObesity is a chronic metabolic disease caused by a combination of environmental and genetic factors.Its essence is mainly the disorder of insulin resistance and energy metabolism in the body,resulting in excessive accumulation and/or abnormal distribution of adipose tissue in the body.IP6K1 is a member of the phosphoinositide kinase family and is widely found in eukaryotic cells and is involved in a variety of life activities.Recent studies have found that IP6K1 is also closely related to the occurrence and development of diseases such as obesity and type 2 diabetes.IP6K1 can affect the body’s insulin resistance and energy metabolism through AKT/PKB signaling pathway and AMPK signaling pathway.However,the research on IP6K1 at home and abroad mainly focuses on the molecular mechanism.There are still vacancies in the study of obese patients,and the relationship between IP6K1 and adiponectin is lack of specific research.To explore the significance of IP6K1 in the development of obesity,and to analyze the correlation between serum IP6K1 and glucose and lipid metabolism evaluation index and adiponectin,in order to explore the pathophysiological mechanism of IP6K1 in obesity and its related metabolic diseases.Objectives1.To observe the difference of serum IP6K1 expression between overweight/obese patients and normal controls,and the correlation between serum IP6K1 and glycolipid metabolism and adiponectin.2.At the cellular level,it is clear how IP6K1 regulates the expression of adiponectin.Methods1.A total of 67 subjects were included in the study.The basic questionnaires were used to collect the basic information of the participants and physical examination.The height,weight,waist circumference and hip circumference of the participants were measured,and the body mass index was calculated according to the measurement results.And waist to hip ratio.Then,2 blood samples were taken from the blood sample of the anterior elbow vein,one was used for the detection of IP6K1 and adiponectin levels by enzyme-linked immunosorbent assay,and the other blood sample was used to detect conventional biochemical indicators.Observed the difference between the two groups of indicators,as well as the correlation between IP6K1 and various biochemical indicators and adiponectin.2.Inducing 3T3L1 preadipocytes to differentiate into mature adipocytes,identifying the differentiation of cells by oil red O staining;interfering with the expression of IP6K1 in differentiated and mature cells,and detecting IP6K1 and adiponectin by RT-PCR and Western Blot Expression of PPARγ;and by interfering with PPARγ expression,it was verified that IP6K1 regulates adiponectin by PPARγ.Resultsl.The serum IP6kl concentration in the overweight/obesity group was 1.20 times that of the normal control group,and the serum adiponectin concentration was 0.78 times of the normal control group(both P<0.05).2.Serum IP6K1 concentration was positively correlated with BMI,waist circumference,waist-to-hip ratio,fasting blood glucose,fasting C-peptide,glycosylated hemoglobin and ALT,and negatively correlated with HDL-C and adiponectin.Among them,HDL-C and adiponectin were independent influencing factors of IP6K1(both P<0.05).3.The critical value of serum IP6K1 concentration for overweight/obesity is 0.062 ng/ml,and the area under the ROC curve(AUC)is 0.646(95%CI 0.581-0.737,P<0.05).The detection sensitivity is 90.3%,specificity.It is 38.9%.4.After overexpression of IP6K1,both RT-PCR and Western Blot showed that the expression of adiponectin and PPARγ was inhibited;on the contrary,the expression of adiponectin and PPARγ was increased after inhibition of IP6K1.5.Increased adiponectin expression in cells overexpressing both IP6K1 and PPARγ compared to cells overexpressing IP6K1.Conclusions1.The IP6K1 in the serum of overweight/obese people is higher than that of the normal population with age and sex.2.IP6K1 was positively correlated with BMI,waist circumference,waist-to-hip ratio,fasting blood glucose,fasting C-peptide,glycosylated hemoglobin and ALT,and negatively correlated with HDL-C and adiponectin.3.In adipocytes,IP6K1 is negatively correlated with PPARγ and adiponectin,and IP6K1 may inhibits the expression of adiponectin by inhibiting the expression of PPARγ.