Extending the glucose/fatty acid cycle: a glucose/adipose tissue cycle

It is now recognized that the WAT (white adipose tissue) produces a variety of bioactive peptides, collectively termed ‘adipokines’. Alteration of WAT mass in obesity or lipoatrophy affects the production of most adipose secreted factors. Since both conditions are associated with insulin resistance, the idea has emerged that certain adipokines might influence insulin action. Among these, tumour necrosis factor α, interleukin-6 and resistin are increased in the obese state and interfere negatively with insulin-mediated processes. Conversely, leptin and adiponectin exert an insulin-sensitizing effect, at least in part by favouring tissue fatty-acid oxidation through AMP-activated kinase activation. Obesity-induced insulin resistance has been linked to leptin resistance and decreased plasma adiponectin, while administration of leptin and adiponectin normalizes plasma levels in lipoatrophic mice and reverses insulin resistance. Thiazolidinedione anti-diabetic agents increase endogenous adiponectin production in rodents and humans, supporting the idea that drugs targeting adipokines might represent a new therapeutic approach to sensitize peripheral tissues to insulin.