Cadmium exposure induces cardiac glucometabolic dysregulation and lipid accumulation independent of pyruvate dehydrogenase activity

Abstract

Context: Suppressed glucose metabolism, elevated fatty acid metabolism and lipid deposition within myocardial cells are the key pathological features of diabetic cardiomyopathy. Studies have associated cadmium exposure with metabolic disturbances. Objective: To examine the effects of cadmium exposure on cardiac glucose homeostasis and lipid accumulation in male Wistar rats. Methods: Male Wistar rats were treated for 21 days as (n ¼ 5): Control, cadmium chloride Cd5 (5 mg/kg, p.o.), cadmium chloride Cd30 (30 mg/kg, p.o). Results:The fasting serum insulin level in this study decreased significantly. Pyruvate and hexokinase activity reduced significantly in the Cd5 group while no significant change in lactate and glycogen levels. The activity of pyruvate dehydrogenase enzyme significantly increased with an increasing dosage of cadmium. The free fatty acid, total cholesterol and triglyceride levels in the heart increased significantly with increasing dosage of cadmium when compared with the control. Lipoprotein lipase activity in the heart showed no difference in the Cd5 group but a reduction in the activity in the Cd30 group was observed. Conclusion:This study indicates that cadmium exposure interferes with cardiac substrate handling resulting in impaired glucometabolic regulation and lipid accumulation which could reduce cardiac efficiency.

Cadmium influence on lipid metabolism in Sprague–Dawley rats through linoleic acid and glycerophospholipid metabolism pathways

“…[ 26 ] Previous studies indicated that Cd exerts negative effects on liver, kidney, bones, and cardiovascular system, which could be resulted from Cd triggering inflammatory processes and lipid accumulation. [ 27,28 ] Some previous studies suggested that kidney and liver dysfunction may lead to changes in lipid metabolism. Other population cohort studies and toxicity studies in mice indicated that kidney and liver toxicity may lead to induce lipid metabolism disorders.…”

The Role of Trace Elements in Cardiovascular Diseases

“…Oluranti et al, also demonstrated an adverse effect of Cd on cardiomyocyte metabolism in a rat study. In detail, Cd leads to a reduction in fasting serum insulin levels and the reduced activity of pyruvate and hexokinase, while the activity of pyruvate dehydrogenase significantly increased after treatment [ 160 ].…”

Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

“…Cd impairs the activity of potassium and sodium ATPase, and this inhibition causes elevated calcium (Ca) levels during hypertension in the smooth muscle. The main reasons for the cardiotoxicity are oxidative stress with attenuated antioxidant defenses and mitochondrial enrichment [ 14 ]. The cardiotoxicity of As is also mediated by increased oxidative stress with low antioxidant levels and mitochondrial enrichment [ 15 ].…”

“…Cd increased the weight of the heart in a rat model [ 47 ]. Similarly, another study showed that toxic chemicals increase organ weight due to the accumulation of lipids and inflammation [ 14 ]. The FFA, TC, and TG levels are increased in the Cd-exposed heart, and in a dose-dependent manner.…”

“…Similarly, the Cd-induced deregulation of lipid levels in the heart is associated with decreased energy levels in the myocardium, further leading to cell death [ 14 ]. In convergence, Cd inhibited mitochondrial fatty acid oxidation and caused hepatic mitochondrial dysfunction and fatty acid oxidation deficiency in a chronic exposure mouse model.…”