Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy: a stable isotope study.
HIV-associated dyslipemic lipodystrophy (HADL) is a heterogeneous syndrome of fat redistribution, hypertriglyceridemia, and insulin resistance, associated with markedly accelerated rates of lipolysis, intraadipocyte and intrahepatic reesterification, and very low-density lipoprotein-triglyceride synthesis and release. The objective of the study was to determine if rosiglitazone can ameliorate these lipid kinetic defects in patients with HADL. Infusions of [(13)C(1)]palmitate and [(2)H(5)]glycerol were used to measure total and net lipolysis, adipocyte and hepatic reesterification, and plasma free fatty acid (FFA) oxidation in 9 men with HADL, before and after 3 months of treatment with rosiglitazone (8 mg/d). Rosiglitazone treatment significantly increased both total lipolysis (R(a) FFA(total) from 3.37 ± 0.40 to 4.57 ± 0.68 mmol FFA per kilogram fat per hour, P < .05) and adipocyte reesterification (1.25 ± 0.35 to 2.43 ± 0.65 mmol FFA per kilogram fat per hour, P < .05). However, there was no change in net lipolysis (R(a) FFA(net) 2.47 ± 0.43 to 2.42 ± 0.37 mmol FFA per kilogram fat per hour), plasma FFA oxidation (0.30 ± 0.046 to 0.32 ± 0.04 mmol FFA per kilogram lean body mass per hour), or FFA flux available for hepatic reesterification (0.59 ± 0.07 to 0.56 ± 0.10 mmol FFA per kilogram fat per hour). There were significant decreases in fasting plasma insulin concentrations and insulin resistance, but not in fasting plasma lipid or glucose concentrations. There was a significant decrease in waist to hip ratio (0.98 ± 0.02 to 0.95 ± 0.02, P < .05) consistent with a significant increase in hip circumference (0.93 ± 0.02 to 0.95 ± 0.02 m, P < .05), without change in waist circumference. Rosiglitazone significantly increased adipocyte reesterification and improved insulin sensitivity, but the potential benefit of these changes was compromised by increase in total lipolysis. Combining rosiglitazone with agents designed to blunt lipolysis could expand depleted peripheral adipose depots in patients with HIV lipodystrophy.
Sekhar
Rajagopal V
RV
Translational Metabolism Unit, Diabetes and Endocrinology Research Center, Baylor College of Medicine, Houston, TX 77030-2600, USA. rsekhar@bcm.edu
Patel
Sanjeet G
SG
D'Amico
Susana
S
Shi
Jianjian
J
Balasubramanyam
Ashok
A
Rehman
Khaleel
K
Jahoor
Farook
F
Visnegarwala
Fehmida
F
D023241:Antiretroviral Therapy, Highly Active; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D002153:Calorimetry, Indirect; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010168:Palmitates / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D049629:Waist-Hip Ratio
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D010168:Palmitates; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005990:Glycerol