Study of the relationship between some nutritional factors, expression of some obesity related micro RNAs, serum level of spexin and metabolic as well as inflammatory status with obesity in 12-18 years old adolescents

Abstract

Abstract Background and aims: The prevalence of childhood obesity has increased dramatically over the past 30 years. Childhood obesity is more likely to become adult obesity and increase the risk of developing disorders such as metabolic syndrome, diabetes mellitus, dyslipidemia, and cardiovascular disorders. The aim of present study was to investigate the relationship between some nutritional factors, expression of some obesity related micro RNAs, serum level of spexin and metabolic as well as inflammatory status with obesity in 12-18 year old adolescents

Methods: 180 children and adolescents (90 obese and 90 normal-weight) with the mean age of 13.73(2.68) were recruited in the present study. The normal-weight and obese groups were matched based on age and gender. All the study participants and their parents were given a full explanation of the study objectives and the methodology, after which, they signed an informed consent form. Height, weight, blood pressure, and waist and hip circumference were obtained. BMI and waist to hip ratio were calculated. General information, physical activity level, depression, anxiety and stress level, pubertal stage and appetite score were measured using relevant questionnaires. Dietary intakes of subjects was assessed by food frequency questionnaire (FFQ). Blood samples of 90 subjects were obtained after an overnight fast of 12 h. Serum spexin, interleukin-10 (IL-10), IL-1β, high-sensitivity C-reactive protein (hs-CRP), fasting glucose, insulin and lipid profile were measure during standard techniques. To evaluate the expression of microRNAs, peripheral blood mononuclear cell (PBMCs) were isolated from peripheral blood. In the next step, RNA was extracted and cDNA was synthesized. Finally, the expression of the desired microRNAs was measured by RT-PCR.

Results: Based on the results of the present study, body mass index, waist and hip circumference, waist to hip ratio and systolic blood presure were significantly greater in the obese adolescents than the normal-weight group (P<0.05). The history of obesity in parents as well as the onset of pregnancy with maternal obesity were higher in obese adolescents than the control group. 47% of obese adolescents had a history of paternal obesity, 65% had a history of maternal obesity, and in 34% of obese teens, their mothers started pregnancy with obesity (P<0.05). In the present study, there were no significant difference between two groups in terms of birth weight, diastolic blood pressure, level of physical activity, stress, anxiety, depression level, puberty and duration of exclusive breastfeeding. Obese adolescents had significantly higher energy, protein, carbohydrates, zinc and selenium intakes (P<0.05). Three dietary based scores including: dietary inflammation index (DII), healthy eating index (HEI) and adherence to the "Dietary Approach to Stop Hypertention" (DASH) diet were calculated. Higher DII score (more pro inflammatory diet) was associated with the increase odds of obesity. Crude OR (CI): 1.79(1.025-3.15), P= 0.04. Model 1 OR (CI): 2.11(1.17-3.83), P = 0.01, and model 2 OR (CI): 1.94(1.06-3.55), P = 0.03. There were no significant difference between the two groups in terms of other two scores. Among the five microRNAs studied (mir15a, mir146a, mir155, mir193 and mir122), the expression levels of mir193 in PBMC of obese adolescents were significantly higher in comparision to normal weight subjects (P<0.05). Median (IQR) of spexin levels were significantly lower in obese vs. normal-weight adolescents. Based on the tertiles of the serum spexin levels, a protective independent effect was observed for the highest tertile of serum spexin concentrations. Crude OR(CI): 0.33(0.11-0.95), P-trend =0.04. Model 1 OR(CI): 0.20(0.05-0.73), P- trend =0.01), Model 2 OR(CI): 0.22(0.05-0.86), P -trend =0.03. Serum spexin concentration was significantly associated with IL-10, fasting Insulin, HOMA-IR and dietary fat intake (P <0.05). Obese adolescents had significantly higher hs-CRP and significantly lower IL-10 in comparision to normal-weight adolescents (P<0.05). 73.3% of obese adolescents had higher hs-CRP levels than normal range (Recommended normal level based on age and sex of adolescents), and only 6.7% of normal-weight adolescents had hs-CRP levels higher than normal range. There was a significant difference between two groups in metabolic syndrome fequency. 31% of obese adolescents met the criteria for metabolic syndrome, And none of the normal-weight adolescents had metabolic syndrome. Obese adolescents had significantly higher SBP, TC, LDL-C, TG, Insulin, HOMA-IR (P<0.001), and significantly lower HDL-C. There was also a significant difference between two groups in terms of hyperinsulinemia and insulin resistance. The frequency of these disorders was significantly higher in obese group than the normal-weight adolescents (P<0.05). There was a significant positive association between mir122 expression level with fasting insulin, HOMA-IR, hs-CRP, TG, dietary chromium intake, and four other microRNAs (P<0.05). The expression level of mir193 showed a significant direct association with fasting insulin, HOMA-IR, hs-CRP level, chromium intake and four other micro RNAs(P<0.05). The expression of mir146 had only a positive association with dietary chromium intake and four other microRNAs(P<0.05). There was also significant association between mir15a expression and fasting insulin, HOMA-IR, chromium intake, and four other micro RNAs (P<0.05).

Conclusions: According to the results of the present study, spexin levels were significantly lower in obese than normal-weight adolescents. The protective independent effect observed for the highest tertile of serum spexin concentrations, and its association with glucose metabolism and immune function, indicated a potential role for this novel peptide in childhood obesity and obesity-related metabolic disorders. Mir193 expression levels in PBMC of obese adolescents were significantly higher than the control group. Significant correlations were observed between the expression of five studied microRNAs and some factors related to glucose metabolism, lipid profile, hs-CRP level and dietary chromium intake. More studies are warranted to confirm these findings and probe into the probable underlying mechanisms.

Keywords: Obesity, Spexin, micro RNAs, Adolescents,Metabolic syndreome, Inflammatory factors