Study finds evidence linking fat loss to the activity of the nervous system

A small Dutch study has shown that HIV-positive patients with fat loss as a side-effect of HIV treatment have high levels of the neurotransmitter noradrenaline in their fat tissue. The investigators believe that this could be evidence of a link between lipoatrophy and alterations in the activity of the nervous system. The study’s findings were presented in the 21^st March edition of AIDS.

In late 2003, the same group of doctors published an article in the journal The Lancet describing their hypothesis that antiretrovirals could cause body fat redistribution through their action on the unconscious ‘autonomic’ nervous system.

They argued that lipoatrophy could be caused by overactivity of the ‘sympathetic’ component of the autonomic nervous system in fat deposits under the skin. Backing up their hypothesis with observations from animal and human studies, they proposed that this could lead to a breakdown of the fat tissue under the skin, leaving other types of fat intact.

Now, the doctors have measured the activity of the sympathetic nervous system and levels of its main signalling chemical noradrenaline in the fat and muscle of seven HIV-positive patients with body fat redistribution. They compared these measurements to those from seven HIV-negative control patients and seven HIV-positive patients who have never taken anti-HIV drugs.

Noradrenaline levels tended to be higher in the muscle and the fat of the patients with lipoatrophy than in the HIV-negative patients. However, when the investigators calculated ratios of noradrenaline levels in the fat to those in the muscle, they found a significantly higher ratio in the patients with lipoatrophy (p

In contrast, the HIV-positive patients without lipoatrophy had similar levels of noradrenaline to the HIV-negative control patients. However, the investigators did not give the ratio of noradrenaline levels for this group of patients.

“The interstitial concentration of noradrenaline in subcutaneous fat relative to that in skeletal muscle tended to be higher in HIV-associated adipose redistribution syndrome (HARS) patients,” the doctors conclude. This is “consistent with an increased noradrenaline content in subcutaneous fat, compared with the other groups."

The investigators did not see any differences in the overall whole-body activity of the sympathetic nervous system, as measured by noradrenaline levels in the blood or by examining the blood pressure and heart rate of the patients.

They did find that the activity of the sympathetic nerves leading to the leg muscles was lower in the patients with lipoatrophy than the other two groups (p

Although their observations fall short of proving that local alterations in the activity of the sympathetic nervous system are responsible for the loss of fat from under the skin, they provide some evidence to support their original hypothesis. However, more research is needed to examine whether changes in the activity of nerves targeting the fat tissue occur in patients with lipoatrophy, and whether these changes can be linked to the effects of anti-HIV drugs in the brain.

“In the context of an unchanged global sympathetic activity, HIV-infected patients with HARS appear to have increased noradrenaline concentrations at the level of skeletal muscle and subcutaneous fat tissue, which may be consistent with the hypothesis that regional changes in autonomic activity contribute to the selective loss of peripheral fat as observed in HARS,” the investigators conclude.

“These findings suggest that disturbances in local sympathetic nervous system activity play a role in this remarkable syndrome, but this requires further investigation.”