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Biomedical subjects

C G Walker

Publications and source records attributed to C G Walker.

5 recordsLinked to original sources

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes.

OBJECTIVE: Leptin secretion in rats is regulated acutely by nutritional state. Insulin plays an important role in this acute nutritional regulation both directly and indirectly through effects on glucose metabolism. The aim of this study was to investigate if the fasting-induced suppression of leptin secretion was reversed by incubation under conditions mimicking nutritional repletion. DESIGN: Leptin secretion and glucose metabolism were measured following incubation with glucose and insulin in adipocytes isolated from fed and fasted rats. RESULTS: Leptin secretion was stimulated by incubation with glucose and insulin in adipocytes isolated from fed but not from fasted rats as was glucose flux through oxidative and lipogenic pathways. Ob expression and intracellular leptin content were decreased in adipocytes isolated from fasted rats throughout the whole incubation period. Suppression of glucose metabolism with cytochalasin B was accompanied by suppression of leptin secretion. The amount of leptin secretion correlated with the glucose incorporated into lipid under insulin-stimulated conditions. CONCLUSIONS: It is proposed that glucose incorporation into lipid, at least during insulin-stimulated conditions, reflects the metabolic status of the adipocyte and may be a more important regulator of leptin production and secretion than circulating glucose or insulin levels.

Adipocytes↗

Accuracy of a computer-assisted navigation system for total knee replacement.

The object of this study was to develop a method to assess the accuracy of an image-free total knee replacement navigation system in legs with normal or abnormal mechanical axes. A phantom leg was constructed with simulated hip and knee joints and provided a means to locate the centre of the ankle joint. Additional joints located at the midshaft of the tibia and femur allowed deformation in the flexion/extension, varus/valgus and rotational planes. Using a digital caliper unit to measure the coordinates precisely, a software program was developed to convert these local coordinates into a determination of actual leg alignment. At specific points in the procedure, information was compared between the digital caliper measurements and the image-free navigation system. Repeated serial measurements were undertaken. In the setting of normal alignment the mean error of the system was within 0.5 degrees . In the setting of abnormal plane alignment in both the femur and the tibia, the error was within 1 degrees . This is the first study designed to assess the accuracy of a clinically-validated navigation system. It demonstrates in vitro accuracy of the image-free navigation system in both normal and abnormal leg alignment settings.

Arthroplasty, Replacement, Knee↗

Insulin determines leptin responses during a glucose challenge in fed and fasted rats.

OBJECTIVE: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms. DESIGN: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison. RESULTS: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r = 0.85) and with the glucose response in fed rats (r = 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose. CONCLUSIONS: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.

Adipose Tissue↗

Dietary modulation of circulating leptin levels: site-specific changes in fat deposition and ob mRNA expression.

In order to study the effects of diet on fat distribution, circulating leptin levels and ob mRNA expression, diets of different macronutrient composition were fed to lean mice and gold thioglucose-obese mice. A high-fat diet and 2 high-carbohydrate diets, one containing mostly high-glycaemic-index starch and the other containing low-glycaemic-index starch were fed ad libitum for 10 weeks and were compared to standard laboratory chow. Weight gain was attenuated by feeding low-glycaemic-index starch in all mice and by feeding a high-fat diet in lean mice. Reduced adiposity was seen in lean mice fed low-glycaemic-index starch, whereas increased adiposity was seen in both lean and obese mice fed on the high-fat diet. Circulating leptin levels, when corrected for adiposity, were decreased in all mice fed either the high-fat diet or the low-GI diet. In epididymal fat pads, decreased ob mRNA expression was seen after both high-fat and high-glycaemic-index starch feeding. These results show that diet macronutrient composition contributes to the variability of circulating leptin levels by the combined effects of diet on fat distribution and on site-specific changes in ob mRNA expression.

Adipose Tissue↗