HIF1A and obesity due to melanocortin 4 receptor deficiency: Systemic metabolic inflammation induced by obesity, diabetes, and gut microbiota dysbiosis further exacerbates testicular dysfunction through the mTOR/HIF-1α signaling axis and the “gut–immune–gonadal axis.” Pharmacological modulation of key immunometabolic regulators, including AMPK, SIRT1, and PPARγ, has been shown to improve sperm quality and hormone levels in experimental models.