ARS | Publication request: METABOLIC BASIS OF HIV-LIPODYSTROPHY SYNDROME

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 18, 2002
Publication Date: April 23, 2002
Citation: SEKAR, R.V., JAHOOR, F., WHITE, A.C., POWNALL, H.J., VISNEGARWALA, F., RODRIGUEZ-BARRADAS, M.C., SHARMA, M., REEDS, P.J., BALASUBRAMANYAM, A. METABOLIC BASIS OF HIV-LIPODYSTROPHY SYNDROME. AMERICAN JOURNAL OF PHYSIOLOGY ENDOCRINOLOGY AND METABOLISM. 2002. v. 283. p. E332-E337.

Interpretive Summary: People infected with the virus that causes AIDS are living longer now due to treatment with new types of drugs such as protease inhibitors, which prevent the virus from multiplying. They are, however, developing a new type of disease called lipodystropy in which their blood sugar and fat levels rise and the fat in their body is redistributed from their limbs to their trunk, chest and shoulder. In the long run high fat levels in the blood can lead to blockage of their arteries and eventually to heart disease. The cause of this new condition is not known. The purpose of our study in healthy men and men infected with the virus and who had lipodystrophy, was to find the changes in fat metabolism that was causing this condition. We found that compared to healthy men, those men with lipodystrophy were breaking down their body fats at a very fast rate. This extra fat was not being used up fast enough to produce energy. As a consequence, it accumulated in the liver and blood causing an elevation in the amount of fat in the blood. This study suggest that drugs that can slow down the rate at which fat is being broken down will be helpful in treating these patients.

Technical Abstract: Human immunodeficiency virus (HIV)-lipodystrophy syndrome (HLS) is characterized by hypertriglyceridemia, low high-density lipoprotein-cholesterol, lipoatrophy, and central adiposity. We investigated fasting lipid metabolism in six men with HLS and six non-HIV-infected controls. Compared with controls, HLS patients had lower fat mass (15.9 +/- 1.3 vs. 22.3 +/- 1.7 kg, P < 0.05) but higher plasma glycerol rate of appearance (R(a)), an index of total lipolysis (964.71 +/- 103.33 vs. 611.08 +/- 63.38 micromol x kg fat(-1) x h(-1), P < 0.05), R(a) palmitate, an index of net lipolysis (731.49 +/- 72.36 vs. 419.72 +/- 33.78 micromol x kg fat(-1) x h(-1), P < 0.01), R(a) free fatty acids (2,094.74 +/- 182.18 vs. 1,470.87 +/- 202.80 micromol x kg fat(-1) x h(-1), P < 0.05), and rates of intra-adipocyte (799.40 +/- 157.69 vs. 362.36 +/- 74.87 micromol x kg fat(-1) x h(-1), P < 0.01) and intrahepatic fatty acid reesterification (1,352.08 +/- 123.90 vs. 955.56 +/- 124.09 micromol x kg fat(-1) x h(-1), P < 0.05). Resting energy expenditure was increased in HLS patients (30.51 +/- 2.53 vs. 25.34 +/- 1.04 kcal x kg lean body mass(-1) x day(-1), P < 0.05), associated with increased non-plasma-derived fatty acid oxidation (139.04 +/- 24.17 vs. 47.87 +/- 18.81 micromol x kg lean body mass(-1) x min(-1), P < 0.02). The lipoatrophy observed in HIV lipodystrophy is associated with accelerated lipolysis. Increased hepatic reesterification promotes the hypertriglyceridemia observed in this syndrome.