HIV lipodystrophy – characterized by peripheral lipoatrophy, with or without central fat accumulation – confers increased metabolic risk. However, the functional activity of HIV lipodystrophic tissue in relation to metabolic risk has yet to be fully explored in vivo through the use of non-invasive imaging techniques. This study assesses the relationship between FDG uptake in various fat depots and metabolic/immune parameters among subjects with HIV lipodystrophy.
Methods
Lipodystrophic men on antiretroviral therapy underwent whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography scans and detailed metabolic/immune phenotyping.
Results
FDG uptake in the subcutaneous adipose tissue (SAT) of the extremities (mean standardized uptake value [SUV] of the arm and leg SAT) was found to correlate with the degree of peripheral lipoatrophy (r=0.7; P=0.01). Extremity SAT FDG uptake was positively associated with homeostasis model assessment of insulin resistance (HOMA-IR; r=0.6; P=0.02) and fasting hyperinsulinaemia (r=0.7; P=0.01), while fat percentage of extremities was not. Furthermore, extremity SAT FDG uptake was significantly associated with CD4+ T-cell count (r=0.6; P=0.05). In multivariate modelling for HOMA-IR, extremity SAT FDG uptake remained significant after controlling for body mass index and tumour necrosis factor-α (R2 for model =0.71, P=0.02; SUV in the extremity SAT β-estimate 12.3, P=0.009).
Conclusions
In HIV lipodystrophic patients, extremity SAT FDG uptake is increased in association with reduced extremity fat and may contribute to insulin resistance. Non-invasive assessments of in situ inflammation using FDG-PET may usefully complement histological and gene expression analyses of metabolic dysregulation in peripheral fat among HIV-positive patients.
References
1.
GrinspoonS., CarrA.Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med2005; 352: 48–62.
2.
ChenD., MisraA., GargA.Clinical review 153: lipodystrophy in human immunodeficiency virus-infected patients. J Clin Endocrinol Metab2002; 87: 4845–4856.
HammondE., McKinnonE., NolanD.Human immunodeficiency virus treatment-induced adipose tissue pathology and lipoatrophy: prevalence and metabolic consequences. Clin Infect Dis2010; 51: 591–599.
5.
ShikumaC.M., HuN., MilneC.Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected individuals with peripheral lipoatrophy. AIDS2001; 15: 1801–1809.
6.
GiraltM., DomingoP., VillarroyaF.Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab2011; 25: 487–499.
7.
SevastianovaK., SutinenJ., KannistoK., HamstenA., RistolaM., Yki-JarvinenH.Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab2008; 295: E85–E91.
8.
TorrianiM., ThomasB.J., BarlowR.B., LibrizziJ., DolanS., GrinspoonS.Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution. J Appl Physiol2006; 100: 609–614.
9.
HadiganC., KaminD., LiebauJ.Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy. Am J Physiol Endocrinol Metab2006; 290: E289–E298.
10.
Bleeker-RoversC.P., van der VenA.J., ZomerB.F-18-fluorodeoxyglucose positron emission tomography for visualization of lipodystrophy in HIV-infected patients. AIDS2004; 18: 2430–2432.
11.
TorrianiM., FitchK., StavrouE.Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome. J Clin Endocrinol Metab2012; 97: E602–E607.
12.
ChristenT., SheikineY., RochaV.Z.Increased glucose uptake in visceral versus subcutaneous adipose tissue revealed by PET imaging. JACC Cardiovasc Imaging2010; 3: 843–851.
13.
WestergrenH., DanielssonA., NystromF.H., StralforsP.Glucose transport is equally sensitive to insulin stimulation, but basal and insulin-stimulated transport is higher, in human omental compared with subcutaneous adipocytes. Metabolism2005; 54: 781–785.
14.
O'RourkeR.W., MetcalfM.D., WhiteA.E.Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. Int J Obes (Lond)2009; 33: 978–990.
15.
KlimcakovaE., RousselB., KovacovaZ.Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat. Diabetologia2011; 54: 876–887.
16.
KlimcákováE., RousselB., Marquez-QuinonesA.Worsening of obesity and metabolic status yields similar molecular adaptations in human subcutaneous and visceral adipose tissue: decreased metabolism and increased immune response. J Clin Endocrinol Metab2011; 96: E73–E82.
17.
EbertB.L., FirthJ.D., RatcliffeP.J.Hypoxia and mitochondrial inhibitors regulate expression of glucose transporter-1 via distinct Cis-acting sequences. J Biol Chem1995; 270: 29083–29089.
18.
LumengC.N., DeyoungS.M., SaltielA.R.Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am J Physiol Endocrinol Metab2007; 292: E166–E174.
19.
MynarcikD.C., McNurlanM.A., SteigbigelR.T., FuhrerJ., GelatoM.C.Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr2000; 25: 312–321.
20.
LakeJ.E., WohlD., ScherzerR.Regional fat deposition and cardiovascular risk in HIV infection: the FRAM study. AIDS Care2011; 23: 929–938.
