Insulin sensitizer also serves as energy-conserving signal to...( physiological role in the central nervo...)

The researchers now report evidence in mice that adiponectin receptors are present in the hypothalamic region of the brain and that some forms of the chemical enter the cerebrospinal fluid from the blood. Once in the brain, adiponectin enhances the activity of a metabolic enzyme called AMP-activated protein kinase (AMPK) to stimulate greater food consumption. Moreover, the researchers found that adiponectin decreased energy expenditure. They also showed that blood and spinal fluid adiponectin levels in the brain normally increase during fasting and decrease after refeeding, suggesting that adiponectin acts mainly during food shortages.

In adiponectin-deficient mice, AMPK activity in the brain slowed, causing the animals to eat less and expend more energy. That action, in turn, made the animals resistant to becoming obese even on a high-fat diet. Moreover, animals lacking adiponectin lost more fat after 12 hours of fasting than normal mice did.

Blood levels of another fat hormone, leptin, are regulated inversely in relation to serum adiponectin levels, the researchers noted.

Thus, central adiponectin/leptin signals may represent the physiological pathway by which hypothalamic AMPK activity and food intake are stimulated during fasting and suppressed after refeeding, they said. In addition to this short-term regulation of food intake and energy expenditure by adiponectin and leptin, these two adipokines may also participate in the long-term regulation of energy homeostasis. The fundamental roles of leptin and adiponectin seem to be to preserve an adequate fat reserve: leptin acts as a satiety signal, and adiponectin acts as a starvation signal.