Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution

Abstract

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 microIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.

Myocardial Steatosis Is an Independent Predictor of Diastolic Dysfunction in Type 2 Diabetes Mellitus

“…In addition, we found an inverse correlation between myocardial triglyceride content and high-density lipoprotein cholesterol levels, adjusted for diabetic state. These data are in line with earlier observations demonstrating that increased serum triglyceride and decreased serum high-density lipoprotein cholesterol concentrations correlate with lipid content in skeletal muscle in patients with human immunodeficiency virus-lipodystrophy (24). High-density lipoprotein cholesterol is considered an important mediator of reverse cholesterol transport, a process that involves the transfer and uptake of free cholesterol from the peripheral tissues, with subsequent delivery to the liver, where it can be eliminated.…”

Management of Fat Accumulation in Patients with HIV Infection

“…The most common site for abnormal fat accumulation in treated HIV patients is the VAT compartment but excess fat has also been detected in the dorsocervical, hepatic, cardiac, intrathoracic, and subcutaneous regions, which may also contribute to the metabolic abnormalities [17][18][19][20]. Increased fat also occurs in the intermuscular [21] and intramyocellular [22] compartments, affecting glucose homeostasis. Although lipoatrophy and lipohypertrophy may be present concurrently and to a variable extent in a given individual, most investigators consider that these are distinct biological entities [23].…”

Steatosis and Diastolic Dysfunction

“…Compared with age-matched controls, nondiabetic human immunodeficiency virus (HIV)-lipodystrophy subjects had significantly increased skeletal TG content (10). Those with HIV-lipodystrophy had the same BMI as controls but had increased central adiposity and insulin resistance.…”