Secondary hyperparathyroidism downregulates lipoprotein lipase expression in chronic renal failure

hyperparathyroidism downregulates lipoprotein lipase expres-sion in chronic renal failure. Am. J. Physiol. 273 (Renal Physiol. 42): F925–F930, 1997.—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 abnormal-ity. 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 anti-bovine 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 reduc-tions 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 amelio-rated 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. parathyroid hormone; hyperlipidemia; cholesterol; triglycer-ides; very-low-density lipoprotein; chylomicrons; fat; muscle CHRONIC RENAL FAILURE (CRF) is commonly accompa-nied by increased plasma triglyceride and very-low-density lipoprotein (VLDL) concentrations (3, 5, 11). This is associated with triglyceride enrichment of VLDL, intermediate-density lipoprotein, low-density lipopro-tein (LDL), and high-density lipoprotein (HDL) par-ticles (3, 20, 26). Moreover, clearance of VLDL and chylomicrons and their remnants, as well as LDL an