17 research outputs found
Reduced Body Weight and Increased Energy Expenditure in Transgenic Mice Over-Expressing Soluble Leptin Receptor
studies have shown that OBRe expression is inversely correlated to body weight and leptin levels. However, it is not clear whether OBRe plays an active role, either in collaboration with leptin or independently, in the maintenance of body weight.To investigate the function of OBRe in the regulation of energy homeostasis, we generated transgenic mice that express OBRe under the control of human serum amyloid P (hSAP) component gene promoter. The transgene led to approximately doubling of OBRe in circulation in the transgenic mice than in wild type control mice. Transgenic mice exhibited lower body weight at 4 weeks of age, and slower rate of weight gain when compared with control mice. Furthermore, transgenic mice had lower body fat content. Indirect calorimetry revealed that transgenic mice had reduced food intake, increased basal metabolic rate, and increased lipid oxidation, which could account for the differences in body weight and body fat content. Transgenic mice also showed higher total circulating leptin, with the majority of it being in the bound form, while the amount of free leptin is comparable between transgenic and control mice.These results are consistent with the role of OBRe as a leptin binding protein in regulating leptin's bioavailability and activity
Studies on secretion from the chromaffin cells of the adrenal medulla
This thesis describes metabolic changes occurring in chromaffin cells
when secreting catecholamine (principally adrenaline), and the factors
involved in maintaining the rate of secretion.
In perfused pig adrenal glands, 31p nuclear magnetic resonance
showed that nucleotide stored with catecholamine in the secretory vesicles
(chromaffin granules) of the chromaffin cell was distinguishable from
cytoplasmic nucleotide. Intragranular pH was 5.52 ± 0.15 (± SD, n=8) in
ischaemic glands and rose (+ 0.22 ± 0.16 (± SD, n=6)) on recovery of
cytoplasmic ATP during perfusion. This suggests that catecholamine
accumulation by the granules is not driven by an ATP-generated pH gradient
in intact tissue, as cytoplasmic ATP did not reduce intragranular pH.
Perfused cortex-free ox adrenal medulla consumed 0.51 ± 0.19 (± SD,
n=8) μmole 02/min/g wet weight after 210-230 minutes of perfusion, and this
rose 30% during 4 minute O.lmM acetylcholine stimulations. This enhancement
correlated with secretion but depended on the mode of stimulation,
indicating that ATP consumption in secretion itself was an inadequate
explanation. The proton-translocating Mg-ATPase of the chromaffin granule
may hydrolyse ATP at its uncoupled rate on entering the plasma membrane
during secretion by exocytosis. 1.4 ± 0.9 (± SD, n=12) moles of
catecholamine were secreted per mole of enhanced oxygen consumption over 16
minutes. From this ratio, the oxygen consumption enhancement is shown to be
much larger than that predicted from uncoupled proton pumping.
Ouabain-sensitive oxygen consumption rose from < 6% to 18 ± 8% (± SD, n=4)
during prolonged acetylcholine stimulation in the absence of calcium,
suggesting that Na,K-ATPase was not responsible for all of the oxygen
consumption enhancement.
On continuous stimulation, secretion showed a biphasic decline in
both pig and ox. A decline was also observed on intermittent stimulation.
Cell death, potential-sensitive calcium gating and acetylcholine receptor
desensitisation were only minor contributors. Little recovery occurred on
resting the tissue for 2-3 hours between stimulations. The results are
explained in terms of depletion of a pool of chromaffin granules adjacent
to the plasma membrane.</p