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SummaryIn-vitro studies have implicated the A1 adenosine receptor (A1AR) of adipocytes in inhibition of lipolysis, stimulation of lipogenesis and enhancement of the action of insulin on glucose metabolism. To determine whether any of these activities were physiologically relevant in an intact animal, A1AR was overexpressed in adipose tissue of transgenic mice. Lower plasma free fatty acid (FFA) levels were observed in the transgenic mice relative to the litter-matched controls, supporting a significant physiological role for adipocyte A1AR in the control of lipolysis. However, no differences were observed in body weights or body composition. On a high fat diet, both the transgenic mice and the litter matched controls, male and female, became equally obese. Unlike the control mice, however, the transgenic mice did not develop insulin resistance, as demonstrated by serum glucose and insulin levels and glucose and insulin tolerance tests. These findings demonstrate that adipocyte A1AR plays an important physiological role in the control of insulin sensitivity in an intact animal and therefore should be considered to be a potential therapeutic target for the treatment of obesity-related insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Study Objective: To image and identify by noninvasive methods the sites of low-density lipoprotein (LDL) catabolism in patients with myeloproliferative disease in whom chronic hypocholesterolemia was previously reported.Study Design: The 99mTechnetium-LDL (Tc-LDL) distribution in patients with myeloproliferative diseases was compared with that in normal subjects. The Tc-LDL distribution was also compared with the distribution and organ uptake of a macrophage-seeking radiotracer. 99mTc-sulfur colloid (Tc-SC).Setting: Major metropolitan referral center and institutional practice.Patients: Three normal subjects, two patients with polycythemia vera, two with post polycythemia myeloid metaplasia, and one with agnogenic myeloid metaplasia. The patients were being managed with hydroxyurea or phlebotomy.Intervention: Ten mCi of Tc-LDL (homologous) was injected intravenously.Measurements and Main Results: Gamma camera images of Tc-LDL biodistribution and organ uptake were obtained 4 hours after injection of the tracer. In normal subjects, the Tc-LDL was predominantly taken up by the liver, with relative nonvisualization of spleen and central or peripheral marrow. Patients with myeloproliferative disease showed marked splenic uptake of Tc-LDL. Peripheral bone marrow uptake extended to the lower tibia in two patients with post-polycythemia myeloid metaplasia. Splenic and bone marrow uptake paralleled that of Tc-SC. Hypercellularity of central and peripheral marrow at the sites of Tc-LDL uptake was confirmed by biopsy specimens. The Tc-LDL uptake, however, was not correlated with collagen fibrosis.Conclusions: These results indicate that spleen and bone marrow are sites of LDL catabolism in patients with myeloproliferative disease and suggest the role of macrophages in the hypocholesterolemia and accelerated LDL catabolism of myeloproliferative disease. [ABSTRACT FROM AUTHOR]