Effects of growth hormone on leptin metabolism and energy expenditure in hemodialysis patients with protein-calorie malnutrition.
The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 +/- 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P: < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P: < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P: < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P: < 0.02). Similarly, variations in leptin levels were directly related to insulin (P: < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P: < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.
Garibotto
Giacomo
G
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Barreca
Antonina
A
Department of Endocrinology and Metabolism, University of Genoa, Genoa, Italy.
Sofia
Antonella
A
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Russo
Rodolfo
R
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Fiorini
Fulvio
F
Imperia Hospital, Genoa, Italy.
Cappelli
Giorgio
G
Sampierdarena Hospital, Genoa, Italy.
Cavatorta
Fosco
F
Imperia Hospital, Genoa, Italy.
Cesarone
Arianna
A
Department of Endocrinology and Metabolism, University of Genoa, Genoa, Italy.
Franceschini
Roberto
R
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Sacco
Paolo
P
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Minuto
Francesco
F
Department of Endocrinology and Metabolism, University of Genoa, Genoa, Italy.
Barreca
Tomaso
T
Division of Nephrology, Department of Internal Medicine, University of Genoa, Genoa, Italy.
D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition; D011446:Prospective Studies; D011502:Protein-Energy Malnutrition / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D006435:Renal Dialysis; D012146:Rest
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D019382:Human Growth Hormone