Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy.
Antiretroviral therapy in human immunodeficiency virus (HIV)-positive patients can induce a lipodystrophy syndrome of peripheral fat wasting and central adiposity, dyslipidemia, and insulin resistance. To test whether in this syndrome insulin resistance is associated with abnormal muscle handling of fatty acids, 12 HIV-1 patients (8 females/4 males, age = 26 +/- 2 yr, HIV duration = 8 +/- 1 yr, body mass index = 22.0 +/- 1.0 kg/m(2), on protease inhibitors and nucleoside analog RT inhibitors) and 12 healthy subjects were studied. HIV-1 patients had a total body fat content (assessed by dual-energy X-ray absorptiometry) similar to that of controls (22 +/- 1 vs. 23 +/- 2%; P = 0.56), with a topographic fat redistribution characterized by reduced fat content in the legs (18 +/- 2 vs. 32 +/- 3%; P < 0.01) and increased fat content in the trunk (25 +/- 2 vs. 19 +/- 2%; P = 0.03). In HIV-positive patients, insulin sensitivity (assessed by QUICKI) was markedly impaired (0.341 +/- 0.011 vs. 0.376 +/- 0.007; P = 0.012). HIV-positive patients also had increased total plasma cholesterol (216 +/- 20 vs. 174 +/- 9 mg/dl; P = 0.05) and triglyceride (298 +/- 96 vs. 87 +/- 11 mg/dl; P = 0.03) concentrations. Muscular triglyceride content assessed by means of (1)H NMR spectroscopy was higher in HIV patients in soleus [92 +/- 12 vs. 42 +/- 5 arbitrary units (AU); P < 0.01] and tibialis anterior (26 +/- 6 vs. 11 +/- 3 AU; P = 0.04) muscles; in a stepwise regression analysis, it was strongly associated with QUICKI (R(2) = 0.27; P < 0.0093). Even if the basal metabolic rate (assessed by indirect calorimetry) was comparable to that of normal subjects, postabsorptive lipid oxidation was significantly impaired (0.30 +/- 0.07 vs. 0.88 +/- 0.09 mg x kg(-1) x min(-1); P < 0.01). In conclusion, lipodystrophy in HIV-1 patients in antiretroviral treatment is associated with intramuscular fat accumulation, which may mediate the development of the insulin resistance syndrome.
Luzi
Livio
L
International Center for Assessment of the Nutritional Status and Clinical Research Unit II, Universita' degli Studi di Milano, 20132 Milan, Italy. luzi.livio@hsr.it
Perseghin
Gianluca
G
Tambussi
Giuseppe
G
Meneghini
Elena
E
Scifo
Paola
P
Pagliato
Emanuela
E
Del Maschio
Alessandro
A
Testolin
Giulio
G
Lazzarin
Adriano
A
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition; D002153:Calorimetry, Indirect; D019069:Cell Respiration; D004734:Energy Metabolism; D005260:Female; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000378:metabolism*
D014280:Triglycerides