Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy: A stable isotope study

Rajagopal V. Sekhar, Sanjeet G. Patel, Susana D'Amico, Jianjian Shi, Ashok Balasubramanyam, Khaleel Rehman, Farook Jahoor, Fehmida Visnegarwala

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 [13C1]palmitate and [2H5]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 FFAtotal 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 (Ra 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.

Original languageEnglish (US)
Pages (from-to)754-760
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume60
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

rosiglitazone
HIV-Associated Lipodystrophy Syndrome
Nonesterified Fatty Acids
Isotopes
Lipolysis
Lipids
Fats
Adipocytes
Insulin Resistance
Fasting
Lipodystrophy
Waist-Hip Ratio
Hypertriglyceridemia
Palmitates
Liver
Waist Circumference

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy : A stable isotope study. / Sekhar, Rajagopal V.; Patel, Sanjeet G.; D'Amico, Susana; Shi, Jianjian; Balasubramanyam, Ashok; Rehman, Khaleel; Jahoor, Farook; Visnegarwala, Fehmida.

In: Metabolism: Clinical and Experimental, Vol. 60, No. 6, 06.2011, p. 754-760.

Research output: Contribution to journalArticle

Sekhar, Rajagopal V. ; Patel, Sanjeet G. ; D'Amico, Susana ; Shi, Jianjian ; Balasubramanyam, Ashok ; Rehman, Khaleel ; Jahoor, Farook ; Visnegarwala, Fehmida. / Effects of rosiglitazone on abnormal lipid kinetics in HIV-associated dyslipidemic lipodystrophy : A stable isotope study. In: Metabolism: Clinical and Experimental. 2011 ; Vol. 60, No. 6. pp. 754-760.
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T2 - A stable isotope study

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AU - D'Amico, Susana

AU - Shi, Jianjian

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AU - Jahoor, Farook

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N2 - 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 [13C1]palmitate and [2H5]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 FFAtotal 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 (Ra 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.

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