CONTEXT: Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities. OBJECTIVE: The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and hypoleptinemia. DESIGN: This was a 6-month, open-label, proof-of-principle pilot study. SETTING: Metabolic ward studies were performed before and 3 and 6 months after leptin treatment. PARTICIPANTS: Participants included eight HIV-infected men with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum leptin less than 3 ng/ml. INTERVENTION: Recombinant human leptin was given by sc injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods). OUTCOME MEASURES: Measures included fat distribution by magnetic resonance imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity by euglycemic hyperinsulinemic clamp; endogenous glucose production, gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope tracer studies; oral glucose tolerance testing; liver fat by proton magnetic resonance spectroscopy; and safety. RESULTS: Visceral fat decreased by 32% (P = 0.001) with no changes in peripheral fat. There were significant decreases in fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002), and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin decreased. Endogenous glucose production decreased during fasting and hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity. Leptin was well tolerated but decreased lean mass. CONCLUSIONS: Leptin treatment was associated with marked improvement in dyslipidemia. Hepatic insulin sensitivity improved and lipolysis decreased. Visceral fat decreased with no exacerbation of peripheral lipoatrophy. Results from this pilot study suggest that leptin warrants further study in patients with HIV-associated lipoatrophy.
CONTEXT: Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities. OBJECTIVE: The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infectedpatients with dyslipidemia and hypoleptinemia. DESIGN: This was a 6-month, open-label, proof-of-principle pilot study. SETTING: Metabolic ward studies were performed before and 3 and 6 months after leptin treatment. PARTICIPANTS: Participants included eight HIV-infectedmen with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum leptin less than 3 ng/ml. INTERVENTION: Recombinant humanleptin was given by sc injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods). OUTCOME MEASURES: Measures included fat distribution by magnetic resonance imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity by euglycemic hyperinsulinemic clamp; endogenous glucose production, gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope tracer studies; oral glucose tolerance testing; liver fat by proton magnetic resonance spectroscopy; and safety. RESULTS: Visceral fat decreased by 32% (P = 0.001) with no changes in peripheral fat. There were significant decreases in fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002), and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin decreased. Endogenous glucose production decreased during fasting and hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity. Leptin was well tolerated but decreased lean mass. CONCLUSIONS:Leptin treatment was associated with marked improvement in dyslipidemia. Hepatic insulin sensitivity improved and lipolysis decreased. Visceral fat decreased with no exacerbation of peripheral lipoatrophy. Results from this pilot study suggest that leptin warrants further study in patients with HIV-associated lipoatrophy.
Authors: Yasuhiko Minokoshi; Young-Bum Kim; Odile D Peroni; Lee G D Fryer; Corinna Müller; David Carling; Barbara B Kahn Journal: Nature Date: 2002-01-17 Impact factor: 49.962
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Authors: Giuseppe Matarese; Claudia La Rocca; Hyun-Seuk Moon; Joo Young Huh; Mary T Brinkoetter; Sharon Chou; Francesco Perna; Dario Greco; Holly P Kilim; Chuanyun Gao; Kalliope Arampatzi; Zhaoxi Wang; Christos S Mantzoros Journal: Proc Natl Acad Sci U S A Date: 2013-02-04 Impact factor: 11.205