Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4±
0.4 vs. 4.5±0.6 ng/ml and 18.9±3.3 vs. 33.9±3.1 ng/μl, respectively; p<0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1±1.2 vs. 4.6±0.3 ng/ml; p<0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.
It is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered protein produced exclusively by adipocytes. A number of studies have shown that obesity, insulin resistance and atherosclerosis are accompanied by decreased adiponectin levels and that adiponectin replacement under experimental settings is able to diminish both insulin resistance and atherosclerosis. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of adiponectin and to discuss its potential in the treatment of insulin resistance and atherosclerosis.
Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear receptor superfamily of ligand-activated transcription factors. PPAR-α
, first of its three subtypes (α, β, γ) has traditionally been considered an important regulator of lipid metabolism while its role in the regulation of insulin sensitivity has not been recognized until recently. Here we summarize the experimental and clinical studies focusing on the role of PPAR-α in the regulation of insulin sensitivity. In most of the experimental studies the activation of PPAR-α in rodents leads to improvement of insulin sensitivity by multiple mechanisms including improvement of insulin signaling due to a decrease of ectopic lipids in
non-adipose tissues and decrease of circulating fatty acids and triglycerides
. In contrast, the effect of PPAR-α agonist in humans is much less pronounced probably due to a lower expression of PPAR-α relative to rodents and possibly other mechanisms. Further clinical studies using more potent PPAR-α agonists on a larger population need to be performed to
evaluate the possible role of PPAR-α in the regulation of insulin sensitivity in humans.