Leptin reduces visceral abdominal tissue (VAT) without reducing limb fat
Simon Collins, HIV i-Base
Hootan Khatani and colleagues from University of California, San Francisco, presented results from an NIH funded, open-label, pilot study looking at the effects of leptin treatment on glucose and fat metabolism in patients with lipoatrophy and hypoleptinaemia. 
While interest in leptin has been discussed at many of these workshops, research into a therapeutic role has been very slow. For an overview of the role of leptin and potential role in HIV-related lipodystrophy, see the HTB report from the Lipodystrophy Workshop four years ago. 
The study enrolled eight HIV-positive men with lipoatrophy (5/8 severe, and two patients also had fat accumulation) with leptin levels <3 ng/ml (range 1.1-2.2ng/ml), dyslipidaemia and insulin resistance. Recombinant human leptin was dosed subcutaneously at 0.1mg/kg BID for the first 3 months and at 0.03 mg/kg BID for a further 3 months.
Treatment increased serum leptin to approximately mean 7 ng/mL at month 3 and 20 ng/mL at month 6 (p=0.03 and 0.008 respectively).
Table 1: Effect of leptin on lipid metabolism
|Total cholesterol (mg/dL)||229 ±16||187 ±12||0.001|
|LDL cholesterol||140 ±8||117 ±8||0.002|
|Non-HDL||204 ±15||158 ±12||0.001|
|HDL||25 ±2||29 ±3||0.07|
|Triglycerides||333 ±79||222 ±51||0.16|
|Free fatty acids (mEq/L)||0.40 ±0.04||0.30 ±0.04||0.04|
|Lipolysis (mg/kg/min)||0.20 ±0.05||0.15 ±0.06||0.02|
Visceral adipose tissue measured by MRI (L4-L5) decreased significantly in all patients, from mean 183 +/- 24 cm2 to 129 +/-24 cm2 (p=0.001) compared to non-statistical changes in subcutaneous adipose tissue, 101 +/-29 cm2 to 90 +/-19 cm2 (p=0.45). The decrease in lipolysis suggested this was an effect in adipose tissue, and the lack of effect on lipoatrophy, that this may be a depot-specific effect.
Leptin also had a generally beneficial effect on lipids (TC, LDL, HDL, non-HDL and TG), see Table 1. Although insulin sensitivity improved in the liver, whole body glucose uptake did not achieve significance.
This small uncontrolled study clearly produced sufficiently optimistic results for this to be studied in larger trials. Similar questions may be as appropriate for leptin as for rHGH – ie cost, side effects, and particularly the durability of the effect after the treatment is stopped.
- Khatani H, Schwartz JM, Sakkas GK et al. Effects of leptin treatment on glucose and lipid metabolism and fat distribution in HIV+ patients with lipoatrophy and hypoleptinemia. 8th IWADRLH, September 2006, San Francisco. Abstract 22.
- Leptin, lipodystrophy and insulin resistance. HIV Treatment Bulletin, November 2002.