Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.

Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide expressed in the nervous system and in endocrine cells, e.g. in pancreatic islets. CART deficient mice exhibit islet dysfunction, impaired insulin secretion and increased body weight. A mutation in the CART gene in humans is associated with reduced metabolic rate, obesity and diabetes. Furthermore, CART is upregulated in islets of type-2 diabetic rats and regulates islet hormone secretion in vitro. While the function of CART in the nervous system has been extensively studied, there is no information on its expression or function in white adipose tissue. CART mRNA and protein were found to be expressed in both subcutaneous and visceral white adipose tissue from rat and man. Stimulating rat primary adipocytes with CART significantly potentiated isoprenaline-induced lipolysis, and hormone sensitive lipase activation (phosphorylation of Ser 563). On the other hand, CART significantly potentiated the inhibitory effect of insulin on isoprenaline-induced lipolysis. CART inhibited insulin-induced glucose uptake and lipogenesis, which was associated with inhibition of PKB phosphorylation. In conclusion, CART is a novel constituent of human and rat adipocytes and affects several biological processes central in both lipid- and glucose homeostasis. Depending on the surrounding conditions, the effects of CART are insulin-like or insulin-antagonistic.

Alterations in cyclic nucleotide phosphodiesterase activities in omental and subcutaneous adipose tissues in human obesity.

OBJECTIVE: To elucidate the activity and expression of cyclic nucleotide phosphodiesterase (PDE) families in omental (OM) and subcutaneous (SC) adipose tissue and adipocytes, and to study alterations in their activity in human obesity. DESIGN: Cross-sectional, translational research study. PATIENTS: In total, 25 obese and 9 non-obese subjects undergoing gastrointestinal surgery participated in the study. RESULTS: Inverse correlations between PDE activities and body mass index (BMI) were seen in both SC and OM adipose tissue. Inverse correlations between total PDE and PDE3 activity and BMI were seen in OM adipocytes but not in SC adipocytes. In both SC and OM adipose tissue of obese patients, total PDE and PDE3 activities were decreased compared with the controls. In SC adipose tissue of Type 2 diabetes (T2D) patients, the PDE activity not inhibitable by PDE3 or PDE4 inhibitors (PDEn) was increased compared with obese non-diabetic patients. In addition to PDE3 and 4 isoforms, PDE7B, PDE9A and PDE10A proteins were also detected in adipose tissue or adipocytes. CONCLUSIONS: Multiple PDE families are present in human adipose tissue and their activities are differentially affected by obesity and T2D.