Metabolic endotoxaemia related inflammation is associated with hypogonadism in overweight men

BACKGROUND Obesity is associated with both impaired testosterone production and a chronic state of low grade inflammation. Previously it was believed that this inflammation was mediated by a decline in the immunosuppressive action of testosterone. However, more recently an alternative hypothesis (GELDING theory) has suggested that inflammation originating from the passage of intestinal bacteria into the circulation (metabolic endotoxaemia) may actually be the cause of impaired testicular function in obese men. The aim of this study is to investigate if metabolic endotoxaemia, as quantified by serum Lipopolysaccharide Binding Protein (LBP), is associated with impaired testicular endocrine function. METHODS A total of 50 men aged between 21 and 50 years (mean 35.1 ± 6.8 years) were assessed for adiposity (BMI, waist circumference and % body fat using bio-impedance), inflammatory status (serum CRP, IL-1β, IL-6, TNFα and LBP) and testicular endocrine function (serum testosterone, estradiol, AMH, LH and FSH). Statistical analysis was performed using Pearson correlation analysis, with log transformation of data where appropriate, and multi-variate regression. RESULTS Overall increasing adiposity (% body fat) was positively associated with metabolic endotoxaemia (LBP, r = 0.366, p = 0.009) and inflammation (CRP r = 0.531, p < 0.001; IL-6 r = 0.463, p = 0.001), while also being negatively correlated with serum testosterone (r = -0.403, p = 0.004). Serum testosterone levels were significantly negatively correlated with inflammation (CRP r = -0.471, p = 0.001; IL-6 r = -0.516, p < 0.001) and endotoxaemia (LBP) after adjusting for serum LH levels (p = -0.317, p = 0.03). Furthermore, serum IL-6 was negatively associated with AMH levels (r = -0.324, p = 0.023), with a negative trend between LBP and AMH also approaching significance (r = -0.267, p = 0.064). CONCLUSIONS Obesity and its associated metabolic endotoxaemia helps initiate a pro-inflammatory state characterised by raised serum IL-6 levels, which in turn is correlated with impairment of both Leydig (testosterone) and Sertoli cell function (AMH). These results open up the potential for new treatments of obesity related male hypogonadism that focus on preventing the endotoxaemia associated chronic inflammatory state.