The Association Between Androgen Deficiency, Obesity And Lipid Metabolism Genes In Males

[Background] With the continuously rapid development of the medical level, the average expectancy life span of worldwide population and the proportion of elderly people are rising, the world is entering the era of aging, which made the reproductive health and the life quality of elderly people important. Controversial results existed in risk factors and the pathogenesis of partial androgen deficiency in the aging male(PADAM). The effect of obesity on androgen level has become a hotspot in recent years. Recent studies show that androgen level of obese patients declines in different degrees and suggests that obesity may be related to the decline of androgen level.【Objective】The present study used cross-sectional study to evaluate the association between obesity and PADAM,and an animal research was used to further explore the relationship between obesity-related lipid metabolism gene expression and androgen deficiency in males.[Methods] The epidemiological survey part of the study is community-based cross-sectional study. Middle-aged men were recruited if they meet the inclusion criteria, a clinical androgen test were carried out to obtain the prevalence of PADAM, as well as a physical examination to assess the prevalence of overweight, obesity, mild abdominal obesity or severe abdominal obesity, and then questionnaires to collect the information of basic demographic characteristics, general health status, PADAM-related factors. After controlling for the age, educational level, work status, disease and drug condition and other potential confounding factors, the association between obesity and PADAM were examined by statistical analysis methods including rank sum test, x test and Logistic regression.In the animal research part of the study, androgen deficiency animal model was established by D-galactose injection method. Significant differences on serum total testosterone (TT), superoxide dismutase (SOD) and malondialdehyde (MDA) were used as the criterion to determine whether the animal model was established succesfully or not. Percoll discontinuous density gradient centrifugation method was used to separate Leydig cells, which were then extracted to get the total RNA after primary cultured for 72h. After that, gene chip method was used to screen differentially expressed genes and semi-quantitative RT-PCR method was used to verify the result of gene chip.【Results】In the epidemiological survey research part,a total of 980 men aged from 40 to 70 participated in the study. The prevalence of PAD AM was 18.01%. Those who with overweight, obesity, mild abdominal obesity and severe abdominal obesity group had a higher risk in PAD AM than their without, ORs were 2.72 (95%CI.1.80-4.11),3.19(95%CI:1.91-5.32),1.67(95%CI:1.10-2.53),and 3.06(95%CI: 1.94-4.82), respectively. After controlling for the age, educational level, work status, disease and drug condition and other potential confounding factors, multivariate factor Logistic regression found that the ORs were 2.51(95%CI:1.65-3.81), 2.95(95%CI:1.74-5.01),1.61 (95%CI:1.05-2.47), and 2.75(95%CI:1.72-4.41), respectively.In the animal research part, compared with control group, androgen deficiency model group (low dose group and high dose group) showed decreased serum total testosterone (TT) and serum superoxide dismutase (SOD) activity and increased malondialdehyde (MDA) content, the differences were statistically significant; Gene chip showed androgen deficiency model group had 5 differentially expressed genes compared with the control group, which were Perilipin, Fabp4, Mgll, Mgl-1, and Lipe; Finally, semi-quantitative RT-PCR results showed that gene expression of Perilipin and its two subtypes were significantly reduced.【Conclusions】First, obesity may be associated with the occurrence of PAD AM; Second, the expression differences of obesity-related lipid metabolism gene Perilipin may be relevant to androgen deficiency in the RNA levels.