Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin

Abstract

Adiponectin or adipocyte complement-related protein of 30 kDa (Acrp30) is a circulating protein produced exclusively in adipocytes. Circulating Acrp30 levels have been associated with insulin sensitivity in adult mice and humans, yet the Acrp30 profile over the lifespan and its hormonal regulation in vivo have not been previously described. Hence, we set forth to determine whether hormonal and metabolic changes associated with sexual maturation, reproduction, aging, and calorie restriction affect Acrp30. In mice, Acrp30 levels increase during sexual maturation by 4-fold in males and 10-fold in females. Neonatal castration (CX) allows Acrp30 of adults to reach female levels. CX in adults does not lead to female Acrp30 levels unless glucocorticoid exposure is elevated simultaneously by implant. Ovariectomy of infant mice does not interfere with the pubertal rise of Acrp30. However, ovariectomy in adults increases Acrp30. Estrogen suppressed Acrp30 in mice and 3T3-L1 adipocytes. In parallel to changes in estrogen action, Acrp30 decreased in late gestation but increased in both calorie-restricted and old (anovulatory) mice. The reduction of Acrp30 in lactating dams is consistent with a suppressive effect of prolactin and a stimulating effect of bromocriptine. In summary, Acrp30 levels in serum are under complex hormonal control and may play a key role in determining systemic insulin sensitivity under the respective conditions. Diabetes 52:268 -276, 2003

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

“…Data on PRL and adiponectin are also inconsistent. Whereas serum adiponectin levels are unchanged in PRLR- [6] or PRL-knockout mice [25], PRL at very high doses inhibits adiponectin production in cultured human adipose tissue and in mice in vivo [6,31]. Lower circulating adiponectin levels were reported in lactating women, with inhibition of adiponectin production in cultured human adipocytes by PRL [32].…”

Adiponectin: a relevant player in PPARγ-agonist-mediated improvements in hepatic insulin sensitivity?

“…28 A characteristic sexual dimorphism is found in mice and humans, with higher levels of the total adiponectin found in females. 29 In terms of complex distribution, the majority of adiponectin in males is present in the LMW form (while the HMW circulates in subnanomolar concentrations), whereas females display a more balanced distribution of the two complexes. 28 …”

“…In ob/ob mice, adiponectin mRNA levels are downregulated as well. 34 Conversely, weight reduction in humans and mice 29,35 leads to a significant increase in adiponectin plasma levels and a concomitant increase in insulin sensitivity. Moreover, the locus encoding the adiponectin gene has been identified as a susceptibility gene for insulin resistance and type 2 diabetes.…”

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

“…Unlike for other adipokines, plasma adiponectin concentrations are inversely correlated with adiposity in humans [8,9]. In addition, total adiponectin is positively correlated with insulin sensitivity in human and rodents [10,11]. In obesity and diabetes, low plasma adiponectin concentrations are related to the degree of hyperinsulinaemia and the severity of insulin resistance [11][12][13].…”

“…In addition, total adiponectin is positively correlated with insulin sensitivity in human and rodents [10,11]. In obesity and diabetes, low plasma adiponectin concentrations are related to the degree of hyperinsulinaemia and the severity of insulin resistance [11][12][13]. Adiponectin and HMW adiponectin levels are negatively correlated with serum triglycerides and positively with HDL particles [14,15].…”