Adiponectin acts in the brain to decrease body weight

Abstract

Adiponectin (ADP) is an adipocyte hormone involved in glucose and lipid metabolism. We detected a rise in ADP in cerebrospinal fluid after intravenous (i.v.) injection, consistent with brain transport. In contrast to leptin, intracerebroventricular (i.c.v.) administration of ADP decreased body weight mainly by stimulating energy expenditure. Full-length ADP, mutant ADP with Cys39 replaced with serine, and globular ADP were effective, whereas the collagenous tail fragment was not. Lep(ob/ob) mice were especially sensitive to i.c.v. and systemic ADP, which resulted in increased thermogenesis, weight loss and reduction in serum glucose and lipid levels. ADP also potentiated the effect of leptin on thermogenesis and lipid levels. While both hormones increased expression of hypothalamic corticotropin-releasing hormone (CRH), ADP had no substantial effect on other neuropeptide targets of leptin. In addition, ADP induced distinct Fos immunoreactivity. Agouti (A(y)/a) mice did not respond to ADP or leptin, indicating the melanocortin pathway may be a common target. These results show that ADP has unique central effects on energy homeostasis.

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

“…AdipoR1 and AdipoR2 are both abundantly expressed in the hypothalamus, particularly in the arcuate nucleus and paraventricular hypothalamus 22. Intracerebroventricular administration of APN in a mouse model of T2DM was shown to decrease body weight, mostly through stimulating energy expenditure 23. Beyond energy regulation, APN may also play other roles in the nervous system.…”

Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?

“…However, while adiposity increases leptin levels, it significantly reduces plasma adiponectin concentrations [17]. Despite their opposing relationships with fat accumulation, adiponectin and leptin both regulate the AMPK pathway to enhance fatty acid oxidation in the target tissues, through either direct action on the AMPK pathway [18,19] or modulation of sympathetic nervous system activity [20].…”

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

“…Central treatment with adiponectin proved more potent than systemic treatment of adiponectin in wild-type and ob/ob mice, further highlighting the brain as an important target for adiponectin action [20]. In addition, adiponectin was shown to induce Fos protein immunostaining and increase hypothalamic corticotrophin-releasing hormone synthesis in the paraventricular nucleus, suggesting the activation of hypothalamic sympathetic circuits [20]. Further evidence suggesting a role for adiponectin in the CNS originates from several studies reporting the levels of adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) in the brain [21] and, more specifically, in mouse hypothalamus and on brain endothelial cells of the BBB [22]; the latter may potentially serve as a transport system for receptor-mediated transcytosis of adiponectin across the BBB.…”

“…Intracerebroventricular (i.c.v.) administration of globular, full-length or Cys-39Ser mutant adiponectin into wild-type and ob/ob mice decreased body weight, the effect being mediated via increased energy expenditure [20]. Furthermore, peripherally administered adiponectin caused an increase in cerebrospinal fluid (CSF) adiponectin, suggesting serum-to-CSF transport [20].…”

“…However, these studies measured the adiponectin levels by RIA in mice only and lacked a more detailed examination of the specific complex distribution of adiponectin. Central treatment with adiponectin proved more potent than systemic treatment of adiponectin in wild-type and ob/ob mice, further highlighting the brain as an important target for adiponectin action [20]. In addition, adiponectin was shown to induce Fos protein immunostaining and increase hypothalamic corticotrophin-releasing hormone synthesis in the paraventricular nucleus, suggesting the activation of hypothalamic sympathetic circuits [20].…”