Lisa A. Kosmiski

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome

ObjectiveTo examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DesignCross-sectional study. SettingHIV primary care practices. PatientsPI-treated patients with lipodystrophy (n = 14) and PI-treated (n = 13) and PI-naive (n = 5) patients without lipodystrophy. Main outcome measuresBody composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. ResultsPI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) × 10−4 (min−1/μU/ml) versus 3.2 × 10−4 and 4.6 × 10−4 (min−1/μU/ml), respectively;P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass;P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. ConclusionsBody fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

DRUGS CAUSING DYSLIPOPROTEINEMIA

Diuretics and beta-blockers have a strong tendency to affect serum lipids adversely, whereas the peripherally acting alpha-blocking agents consistently result in beneficial effects. Most of the other antihypertensive agents (calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists, and drugs that act centrally) are lipid neutral. The effect of steroid hormones varies with the drug, dose, and route of administration. In general, androgens lower HDL-C and have a variable effect on LDL-C. The effects of progestins vary greatly depending on their androgenicity, and estrogens are beneficial except when hypertriglyceridemia occurs with oral estrogens. Glucocorticoids raise HDL-C and may also increase triglycerides and LDL-C. Retinoids increase triglycerides and LDL-C and also reduce HDL-C. Interferons can cause hypertriglyceridemia. Following organ transplantation, a dyslipidemia often ensues. This is caused in part by the medications used to prevent rejection (glucocorticoids, cyclosporine, and FK-506) and requires close attention and, in some patients, drug therapy to prevent coronary artery disease.

Fat distribution is altered in HIV‐infected men without clinical evidence of the HIV lipodystrophy syndrome

To determine if fat distribution is altered in HIV‐infected men without clinical evidence of lipodystrophy.

Chronic Starvation Secondary to Anorexia Nervosa Is Associated With an Adaptive Suppression of Resting Energy Expenditure

BACKGROUNDnChronic starvation is accompanied by a reduction in resting energy expenditure (REE). It is not clear whether this is due mainly to a reduction in body mass or also involves a significant reduction in the cellular metabolic rate of the fat-free mass (FFM).nnnOBJECTIVESnThe main goal was to compare measured REE (REEm) with REE predicted by dual-energy X-ray absorptiometry modeling of organ-tissue mass (REEp) in malnourished patients with severe anorexia nervosa (AN) and in healthy lean control subjects. REE adjusted for FFM and fat mass was also compared between the groups.nnnDESIGNnThis was a cross-sectional study of 30 patients with AN and 25 lean control subjects. REE was measured by indirect calorimetry. Body composition was modeled using dual-energy X-ray absorptiometry, and REE was predicted for each group based on organ-tissue mass.nnnRESULTSnREEm was significantly lower than REEp in subjects with AN (854 ± 41 vs 1080 ± 25 kcal/d, P < .001), but not in control subjects. In addition, REE adjusted for both FFM and fat mass was significantly lower in the subjects with AN (1031 ± 37 vs 1178 ± 32 kcal/d, P < .01). Finally, compared with the lean control subjects, both organ and skeletal muscle mass were approximately 20% smaller in subjects with AN.nnnCONCLUSIONSnChronic starvation is accompanied by a significant reduction in the metabolic rate of the FFM. The organs and/or tissues accounting for this are unknown. In addition, this study suggests that protein is mobilized proportionately from organs and skeletal muscle during starvation. This too may be an adaptive response to chronic starvation.

Dual-energy X-ray absorptiometry modeling to explain the increased resting energy expenditure associated with the HIV lipoatrophy syndrome

BACKGROUNDnThe HIV lipoatrophy syndrome is characterized by loss of subcutaneous fat and is associated with increased resting energy expenditure (REE). Recently, dual-energy X-ray absorptiometry (DXA) modeling of organ-tissue mass combined with specific organ-tissue metabolic rates has been used to gain further insight into the relation of the lean body mass to REE and to better understand differences in REE between groups.nnnOBJECTIVEnThis study examined the organ-tissue basis of the increased REE shown in HIV lipoatrophy.nnnDESIGNnREE was measured in 29 HIV-infected patients with lipoatrophy and in 29 HIV-infected and 19 healthy control subjects. Five organ-tissue mass components (brain, bone, skeletal muscle, adipose tissue, and residual mass) were calculated with the use of DXA modeling and body weight.nnnRESULTSnDXA modeling showed no significant differences in predicted REE between the 3 groups. However, measured REE was significantly greater in subjects with lipoatrophy than in control subjects. Measured REE remained significantly greater in lipoatrophy subjects after routine adjustment for lean body mass and after adjustment for each organ-tissue mass component. Finally, DXA and regression modeling of REE suggests that increased energy expenditure in skeletal muscle may account for the resting hypermetabolism of patients with HIV lipoatrophy.nnnCONCLUSIONSnIncreased REE in subjects with HIV lipoatrophy cannot be explained by differences in organ-tissue mass as modeled by DXA. Instead, DXA and regression modeling of REE suggests that skeletal muscle is hypermetabolic in patients with HIV lipoatrophy. This may be a form of adaptive thermogenesis in response to an inability to store triglyceride fuel in a normal manner.

Brown fat activity is not apparent in subjects with HIV lipodystrophy and increased resting energy expenditure.

The HIV lipodystrophy (LD) syndrome is associated with increased resting energy expenditure (REE), but the basis of this hypermetabolism has not been determined. The objective of this pilot study was to determine if brown fat is activated in subjects with HIV LD and increased REE. In this descriptive study of four subjects with HIV LD and marked hypermetabolism, REE was measured by indirect calorimetry and brown fat activity was determined by 18F‐fluorodeoxyglucose (FDG) positron‐emission tomography (PET) combined with anatomic computed tomography (CT). Brown fat activity was not apparent in any subject with HIV LD and resting hypermetabolism. Therefore, brown fat activation is unlikely to be the principal cause of the increased REE associated with the HIV LD syndrome. Evidence of adaptive thermogenesis has been demonstrated in this syndrome, but this study suggests that tissues other than brown adipose tissue (BAT) are responsible. Further understanding of the chronic hypermetabolism associated with HIV LD could provide new insights into the regulation of energy balance.