The main negative effects of over-adiposity on the H-P-O axis are exerted directly, through a decreased pituitary LH pulse amplitude and mean LH release without changing its frequency, impairing luteal phase [4], or indirectly mainly through metabolic changes coexisting with obesity such as hyperinsulinemia and hyperleptinemia, that exerts pro-inflammatory activities, stimulating immune cells and also fueling insulin resistance [20] and LGCI. This evidence concerns the gene PLOD1 and obesity due to melanocortin 4 receptor deficiency.