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In obese (fa/fa) rats both the total (-)-isoprenaline- and NaF-stimulated adenylate cyclase activities of interscapular brown-adipose-tissue (IBAT) plasma membranes were decreased as compared with lean rats by 40 and 38% respectively. An acute treatment with Ro 16-8714 increased (-)-isoprenaline- and NaF-stimulated adenylate cyclase activities by 2.5- and 2.0-fold respectively, and beta-adrenoceptor number 2.8-fold in obese rat IBAT, but it had no effect on these parameters in lean rats. It increased mRNA for mitochondrial uncoupling protein in both lean and obese rats to the same extent.

OBJECTIVES: To assess the effects of intracerebroventricular (icv) leptin administration on rats fed ad libitum or fasted on 3 H GDP binding to brown adipose tissue (BAT). SUBJECTS: Groups of 5 ± 6 ten-week-old male Wistar rats. EXPERIMENTAL DESIGN: An icv cannula was inserted and unilateral denervation of interscapular brown adipose tissue (BAT) was performed 5 d before each study. Thereafter, leptin was infused icv during 72 h while rats were fed ad libitum or fasted. Vehicle-infused, pair-fed or fasted rats were used as controls. MEASUREMENTS: 3 H GDP binding to innervated and denervated BAT mitochondria. RESULTS: 3 H GDP binding to innervated or denervated BAT of rats fed ab libitum compared to vehicle-infused, pair-fed rats was not increased by icv leptin. 3 H GDP binding was lower in fasted than in fed rats, and the difference was larger in innervated than denervated BAT. Icv leptin increased 3 H GDP binding by 30% in innervated, and by 51% in denervated BAT (P`0.05) in fasted rats. CONCLUSIONS: Icv leptin does not increase 3 H GDP binding to BAT of rats fed ad libitum compared to pair-fed (foodrestricted) rats. In contrast, icv leptin produces a mild stimulation of 3 H GDP binding to BAT of fasted rats. This effect is not mediated by the sympathetic nervous system, because it is observed in both innervated and denervated BAT. These results are compatible with the concept that, in fasting rats, the decrease in leptin secretion contributes to the reduction in 3 H GDP binding to BAT mitochondria.

ABSTRACT. Bw gain is controlled by energy intake on one hand and expenditure on the other. The components of energy expenditure are basal metabolism, exercise induced thermogenesis and adaptive UNCOUPLING PROTE/N-1 (UCP1)In rodents, brown adipose tissue (BAT) is an important site of adaptive thermogenesis. Cold exposure has for long been known to induce, via stimulation of the sympathetic nervous system, an increase in BAT thermogenesis referred to as adaptive cold-induced thermogenesis (CIT), (1). Furthermore, it has been observed that voluntary overeating induced in rats by the administration of a palatable, so-called "cafeteria" diet also induced an increase in BAT thermogenesis which was called adaptive diet-induced thermogenesis (OIT) (2).The main producer of heat in BAT is the uncoupling protein-1 (UCP1). This mitochondria inner membrane protein uncouples oxidative phosphorylation by dissipating the proton gradient generated by the re-oxidation of NAOH H+ in the respiratory chain. The UCP1-mediated proton transport requires the presence of fatty acids and is specificalIy inhibited by purine di-and triphosphate nucleotides (3). The consequence of UCP1 activity is a decrease in the amount of ATP formed by the ATP synthase and energy dissipation as heat. UCP1 knockout mice were generated and they were unable to maintain their body temperature upon cold exposure but did not become obese (4).These data confirmed the importance of UCP1 in Key-words: ßTadrenoceptor. uncoupling CIT and suggested that, in UCP1 knockout mice, alternative mechanisms for maintaining body mass wh ich could not protect against the cold were turned on, In humans, BAT is present in newborn babies and decreases in 4-6 months after birth (5, 6). It is therefore generally believed that there is no UCP1 in human adults. THE ßTADRENOCEPTOR -UCP1 AX/SThe family of the ß-adrenoceptors were considered to consist of ß1-and ß-rsubtypes until1989 when a third subtype was cloned (7). This third subtype called the ß3-adrenoceptor was found to be the predominant ß-subtype in rodent BAT and white adipose tissue (WAT) (8,9). When the BAT sympathetic nervous system activity is increased by cold exposure or overfeeding, the stimulatory effect on UCP1 activity and expression is therefore mediated essentially by the ß3-adrenoceptor (9). Therefore, the ß3-adrenoceptor-UCP1-axis is a major determinant of rodent adaptive thermogenesis, The ß3-adrenoceptor was found to be down-regulated in obese fa/fa Zucker rat BAT and WAT (8) and in obese ob/ob mouse adipose tissues compa red to lean animals (10). In ß3-adrenoceptor knockout mice, the capacity to adapt to a cold environment was fully preserved, but there was an increase in fat deposition under basal conditions and in response to a high fat diet (11). These data confirmed the importance of the ß3-adrenoceptor in OIT and suggested that, in the ß3-adrenoceptor knockout mice, alternative mechanisms for maintaining body temperature were turned on. In rodents, cold exposure was found to recruit mul- A.P. Russe 1...

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