Secondary hyperparathyroidism downregulates lipoprotein lipase expression in chronic renal failure

In a recent study, we found marked downregulation of lipoprotein lipase (LPL) gene expression in fat, myocardium, and skeletal muscle of rats with chronic renal failure (CRF). Recently, hepatic lipase expression was shown to be depressed in CRF rats, and parathyroidectomy (PTX) was shown to reverse this abnormality. This study was undertaken to determine whether down-regulation of LPL expression in CRF is due to secondary hyperparathyroidism. Accordingly, LPL mRNA (Northern analysis), protein mass (Western analysis using mouse antibovine LPL monoclonal antibody, 5D2), and catalytic activity of the fat pad and soleus muscle were compared in five-sixths-nephrectomized male rats (CRF), parathyroidectomized CRF rats, and sham-operated control animals. The CRF animals exhibited marked hypertriglyceridemia and significant reductions of fat and skeletal muscle LPL mRNA abundance, protein mass, and catalytic activity (P < 0.05 vs. controls, for all parameters). PTX completely normalized the LPL mRNA, protein mass, and enzymatic activity and partially ameliorated the CRF hypertriglyceridemia (P < 0.05 vs. CRF group, for all parameters). Thus secondary hyperparathyroidism is responsible for impaired LPL expression in experimental CRF. This abnormality is completely corrected by PTX.