Abnormal lipid metabolism down-regulates adenosine triphosphate synthase β-subunit protein expression in corpus cavernosum smooth musclein vitroandin vivo

Abstract

Metabolic syndrome is closely related to erectile dysfunction (ED), and hyperlipidaemia is considered a major risk factor for ED. Adenosine triphosphate (ATP) synthase is believed to play an important role in metabolic syndrome; it has been hypothesised that ATP synthase contributes to ED development. We have verified this hypothesis using primary cultured human corpus cavernosum smooth muscle (HCCSM) cells treated with excessive free fat acid (FFA) and a high-fat diet (HFD) mouse model. Our results showed that high fatty factors could cause lipid accumulation in HCCSM cells, which could result in abnormal lipid metabolism, such as high levels of triglycerides, cholesterol and glucose in the HFD mice. There was a remarkable down-regulation of ATP synthase and p-Akt after in vivo and in vitro excessive FFA treatments. These results indicated that abnormal lipid metabolism could induce ATP synthase down-regulation via the Akt phosphorylation pathway and that ATP synthase may be a target of lipotoxicity in corpus cavernosum smooth muscle cells.

Do penile haemodynamics change in the presence of hydrogen sulphide (H2S) donor in metabolic syndrome-induced erectile dysfunction?

“…It has been consistently shown that the prevalence of ED is significantly correlated with age and vascular risk factors including atherosclerosis, hypertension, hypercholesterolaemia, diabetes and lifestyle issues (Musicki et al., ). ED is known as one of the symptoms of cardiovascular disease and significantly associated with metabolic syndrome (metS) (Chaudhary, Shamsi, Tan, Chen, & Xing, ; Liu et al., ). The metS is a progressive disease, which is manifested by combination of hypertension, abdominal obesity, insulin resistance, hyperglycaemia, dyslipidaemia, glucose intolerance and at various clinical conditions associated with type 2 diabetes and vascular pathologies.…”

Mitochondrial ATP synthase regulates corpus cavernosum smooth muscle cell function in�vivo and in�vitro

“…In a previous study, hyperglycemia has been demonstrated to impair mitochondrial function and inhibit ATP synthase activity, leading to reduced levels of ATP production (28). Liu et al (5) showed that high glucose resulted in abnormal lipid metabolism, in turn leading to a decrease in ATP synthase expression through the Akt phosphorylation pathway in CCSMCs, suggesting that ATP synthase is essential for CCSMC function in hyperglycemia. In the present study, continuous exposure to high glucose reduced the expression of the F 1 -ATP synthase protein in both rat CCSMCs and smooth muscle tissues from the corpus cavernosum in diabetic rats.…”

“…Corpus cavernosum smooth muscle function involves a plethora of complex intracellular events and extracellular signals (3,4). Since smooth muscle cell (SMC) function depends heavily on mitochondrial activity a strong association exists between mitochondrial dysfunction and dysfunction in the corpus cavernosum smooth muscle (5). In particular, long-term hyperglycemia has been reported to reduce mitochondrial biogenesis, increase the ADP/ATP ratio, induce ultra-structural changes and markedly increase the production of reactive oxygen species (ROS) (6)(7)(8).…”

Current status and prospects of diabetes mellitus induced erectile dysfunction: A bibliometric and visualization study

“…Risk factors for ED include age, obesity, smoking, depression, and metabolic disorders ( 3 ), which are more common in middle-aged and elderly men with diabetes ( 4 , 5 ). Long-term hyperglycemia in diabetic patients induces the production of large amounts of reactive oxygen species that impair mitochondrial and smooth muscle function in the corpus cavernosum, which leads to ED ( 6 , 7 ). In different regions of the world, the prevalence of diabetes mellitus-induced erectile dysfunction (DMED) ranges from 35.8% to 86.1% ( 8 ), and 12% of diabetic patients have ED as the first symptom ( 9 ).…”