Regulation of Adiponectin in Human Immunodeficiency Virus-Infected Patients: Relationship to Body Composition and Metabolic Indices
Qiang Tong,
Jean-Louis Sankalé,
Colleen M. Hadigan,
Guo Tan,
Eric S. Rosenberg,
Phyllis J. Kanki,
Steven K. Grinspoon and
Gökhan S. Hotamisligil
Division of Biological Sciences and Department of Nutrition (Q.T., G.T., G.S.H.), and Department of Immunology and Infectious Diseases (J.-L.S., P.J.K.), Harvard School of Public Health, Boston, Massachusetts 02115; and Combined Program in Pediatric Gastroenterology and Nutrition (C.M.H., S.K.G.), Program in Nutritional Metabolism (C.M.H., S.K.G.), and Division of Infectious Disease (E.S.R.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
Address all correspondence and requests for reprints to: Dr. Gökhan S. Hotamisligil, Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115. E-mail: ghotamis{at}hsph.harvard.edu; or Dr. Steven K. Grinspoon, Director, Program in Nutritional Metabolism, Massachusetts General Hospital, Harvard Medical School, LON207, Fruit Street, Boston, Massachusetts 02114. E-mail: sgrinspoon{at}partners.org.
HIV-related lipodystrophy is characterized by adipose redistribution,dyslipidemia, and insulin resistance. Adiponectin is an adipose-derivedpeptide thought to act as a systemic regulator of glucose andlipid metabolism. We investigated adiponectin concentrationsin 10 HIV-infected patients during acute HIV infection (viralload, 2.0 x 106 ± 1.0 x 106 copies/ml) and then 6–8months later, as well as cross-sectionally in 41 HIV-infectedpatients (21 with evidence of fat redistribution and 20 withoutevidence of fat redistribution) in comparison with 20 age- andbody mass index-matched healthy control subjects. Circulatingadiponectin concentrations did not change with treatment ofacute HIV infection (5.8 ± 0.4 vs. 5.9 ± 0.7 µg/ml,P = 0.96) but were reduced in patients with chronic HIV infectionand fat redistribution (7.8 ± 0.9 µg/ml), comparedwith age- and body mass index-matched HIV-infected patientswithout fat redistribution (12.7 ± 1.7 µg/ml) andhealthy control subjects (11.9 ± 1.7 µg/ml, P <0.05 vs. HIV-infected patients without fat redistribution andvs. control subjects). Adiponectin concentrations correlatedwith body composition [correlation coefficient (r) = -0.47,P = 0.002 vs. trunk fat:total fat; r = 0.51, P < 0.001 vs.extremity fat:total fat], insulin response to glucose challenge(r = -0.36, P = 0.03), triglyceride (r = -0.39, P = 0.01), andhigh-density lipoprotein (r = 0.37, P = 0.02) among the HIV-infectedpatients. Adiponectin remained a significant correlate of insulinresponse to GTT, controlling for medication use and body compositionchanges in HIV-infected patients. These data suggest a strongrelationship between adiponectin and body composition in HIV-infectedpatients. Changes in adiponectin may contribute to the metabolicdysregulation in this group of patients.
This work was supported by Grant R01-DK-59535 (to S.K.G.), NIHGrants AI-43879 and AI-467274 (to F.J.K.), and a research grant(to G.H.S.) from Bristol-Myers Squibb Co. Pharmaceutical ResearchInstitute (Princeton, NJ).
Abbreviations: AUC, Area under the curve; BMI, body mass index;CT, computed tomography; DEXA, dual-energy x-ray absorptiometry;HAART, highly active antiretroviral therapy; HDL, high-densitylipoprotein; LDL, low-density lipoprotein; NRTI, nonnucleosidereverse transcriptase inhibitor; PI, protease inhibitor; SAT,sc adipose tissue; TAT, total abdominal cross-sectional area;VAT, visceral adipose tissue.
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