Chronic renal failure, parathyroid hormone and fatty acids oxidation in skeletal muscle.
Fatty acids are an important source of skeletal muscle energy, and certain data suggest oxidation of long-chain fatty acids (LCFA) may be impaired in uremia. This abnormality may in part be responsible for uremic myopathy. Uremia is associated with hyperparathyroidism and PTH affects muscle metabolism; PTH enhances muscle proteolysis and impairs muscle bioenergetics, and it is possible that PTH also affects fatty acids oxidation. The present study examined in rats the effects of 4 days administration PTH and of 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of LCFA and short-chain fatty acids (SCFA). Both 1-84 and 1-34 PTH impaired oxidation of LCFA but not of a SCFA (beta-hydroxybutyric acid) and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands had also impaired oxidation of LCFA and of CPT activity. Parathyroidectomy in CRF rats normalized these abnormalities. Carnitine contents of muscle were not altered. The data show that PTH excess in normal or in CRF rats is associated with impaired oxidation of LCFA and this effect is due to reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation. The data demonstrate another toxic effect of PTH on muscle in CRF and provide an additional pathogenic mechanism for uremic myopathy.
Smogorzewski
M
M
Department of Medicine, University of Southern California, School of Medicine.
Piskorska
G
G
Borum
P R
PR
Massry
S G
SG
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide; D014511:Uremia / Q000378:metabolism
D005227:Fatty Acids; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D002334:Carnitine O-Palmitoyltransferase