Differential effects of noradrenaline and glucagon on lipolysis and fatty-acid utilization in brown adipose tissue.

The relative effects of noradrenaline (300 pM-3 microM) and glucagon (30 pM-300 nM) upon lipolysis and fatty acid utilization rates in brown adipose tissue from warm- (WA) and cold-acclimated (CA) rats, were: lipolytic sensitivity and responsiveness to the agonists were reduced in CA tissue; in CA tissue, at 300 pM, glucagon promoted fatty acid utilization more than noradrenaline; glucagon at 300 pM increased fatty acid utilization in WA tissue. The data suggest that glucagon has a physiological role in brown adipose tissue, modulating events subsequent to NA- and glucagon-induced lipolysis, promoting fatty acid utilization.

A high-precision automatic closed-circuit respirometer for small animals.

An automatic apparatus for the continuous measurement of O2 consumption of small laboratory animals is described. By use of a high-sensitivity pressure transducer with associated circuitry together with a peristaltic O2 delivery system, the closed respirometer chamber is maintained at atmospheric pressure +/- 0.5 mmH2O. O2 delivery is measured to within 0.25 ml by recording rotations of the peristaltic pump, following calibration by the withdrawal of a preset volume of air from the chamber. Static trials (with the chamber empty) indicate a high degree of reproducibility of data with the chamber pressure remaining at atmospheric pressure +/- 0.5 mmH2O as a result of the proportional, as opposed to fixed-volume, delivery of O2. Trials with mice and rats have likewise produced data with a high degree of reproducibility.

Nutritional status and clinical outcome in elderly female surgical orthopaedic patients.

The possible relationship between nutritional status and clinical outcome following orthopaedic hip surgery was investigated. The nutritional status of 60 elderly female patients admitted for elective total hip replacement (THR) and emergency fractured neck of femur surgery (FNF) was measured over time. Specific measures of clinical outcome, including well-being and functional status, were monitored during hospital stay and at 4, 8 and 26 weeks following discharge. Patients were allocated to a high nutritional risk group where any three of the following were less than the 5th percentile value: serum albumin, haemoglobin, triceps skinfold thickness, mid-upper arm muscle circumference and body weight. Using this definition, malnutrition was present in 4% of THR patients and 41% of FNF patients. It was found that the high risk patients had significantly longer convalescence periods, (median stay 27.5 days compared with 0 days, P < 0.0009), and a greater proportion were dependent upon walking frames at 6 months (46% compared with 11%, P < 0.01). Fifty percent of the high risk patients had been living independently prior to admission, in contrast only 29% had returned to their homes at 6 months after discharge. The results indicate an apparent link between clinical outcome and nutritional status based upon the allocation procedure employed, which has the potential for ensuring cost-effective nutritional intervention.

Effect of a surfactant, Tween 80, on the formation and secretion of chylomicrons in the rat.

Effects of Tween 80, a nonionic surfactant, on size and number of chylomicrons (CM) secreted during lipid absorption in the rat model are reported. Fasted rats were loaded with either 154 mM NaCl or 25% (w/w) olive oil emulsion in 154 mM NaCl with 0, 0.1, 1 or 10% (w/w) Tween 80. After 3 h, either mesenteric lymph or blood was collected and their triacylglycerol-rich lipoprotein fraction (Sf>20 and Sf>400, respectively) isolated. Triacylglycerol (TAG) and apolipoprotein B48 (apoB48) concentrations in the lipoprotein fractions were assayed and their fluxes (lymph) calculated. TAG:apoB48 ratios, indicative of CM size, were determined. The data support the hypothesis that fat loading is accommodated mainly by increased average size, rather than number, of CM. Co-administration of Tween 80 with olive oil resulted in a significant increase in CM apoB48 secretion into the mesenteric lymph duct and in an increased concentration of apoB48 in the blood (Sf>400). Also, Tween 80-treated groups exhibited smaller mean CM size relative to the olive oil only group in both lymph and blood. The observed effect on CM size and number did not appear to be dose dependent at concentrations of Tween 80 above 0.1% (w/w). Incorporation of Tween 80 in the diet at 1 or 10% (w/w) concentrations reduced the TAG concentration in the stools; however, a significant increase in water content was observed at 10% (w/w) concentration. In conclusion, Tween 80 at 1 or 10% (w/w) doses can improve the efficiency of the digestive system to absorb dietary fat but at high concentrations (10%, w/w) it appeared to have a toxic or irritating effect on the gastrointestinal system. More importantly, the effect of Tween 80 on size and number of CM is a condition that favours a delay in their clearance rate.

Distributions and seasonal variability of pH and alkalinity in the Tweed Estuary, UK.

Monthly axial profiles of the Tweed Estuary were carried out between July 1996 and August 1997 as part of the UK Natural Environment Research Council Land Ocean Interaction Study. During these surveys, master variables and a range of chemical constituents, including pH and total alkalinity, were measured between the mouth of the estuary, at Berwick-upon-Tweed, and the freshwater tidal reach, at Union Bridge, approximately 10 km up-estuary. Alkalinity and pH showed clear seasonal variations in values within the lower salinity region of the estuary, and these could be related largely to changes in river flows, and hence to variations in the ratios of the source waters. River waters at high flows were dominated by poorly buffered surficial runoff, and pH and alkalinity values were low; conversely at low flows, groundwaters rich in weathered bedrock ions dominated the river water, and pH and alkalinity values were significantly higher. Biological production and respiration also had an effect on this seasonal variability, although this was secondary. The behaviour of pH and alkalinity within the estuary appeared generally conservative, although apparent non-conservative distributions were observed in the freshwater tidal reach. In a number of cases this behaviour could be attributed to biological activity. Estimated values of the excess partial pressures of CO2 within the fresh-water tidal reach were low (< 4), reflecting the relatively pristine character of the Tweed. During the spring and summer, CO2 was significantly undersaturated with respect to the atmosphere; extensive production by bed-anchored macroalgae was probably the reason for this, although the effects of water column algae cannot be discounted. In winter, production was minimal and respiration more important. As a result, partial pressures within the water column increased to a maximum of approximately four times atmospheric. Only infrequently was the CO2 in equilibrium between the river and atmosphere, suggesting that the tidal reach of the Tweed is a dynamic environment with respect to carbon cycling processes.

Seasonal variability of salinity, temperature, turbidity and suspended chlorophyll in the Tweed Estuary.

Results are presented from a campaign of measurements that were undertaken to examine seasonal variability in physical and chemical fluxes and processes within the Tweed Estuary during the period September 1996-August 1997. The study utilised monthly surveys, each of approximately 1 week duration. This article interprets a subset of the salinity, temperature, turbidity [suspended particulate matter (SPM) levels] and chlorophyll a data. Measurements discussed here were obtained throughout the estuary during high-speed transects that covered the region between the tidal river and the coastal zone. Longitudinal distributions of surface salinity depended strongly on freshwater runoff. During high runoff the surface salinity was low and the freshwater-saltwater interface (FSI) was located close to the mouth. The reverse was true at times of low runoff. Salinity stratification was generally strong. During the surveys, river runoff temperatures ranged from approximately 2 to 18 degrees C and coastal waters (approximately 33 salinity) from approximately 6 to 15 degrees C. Turbidity was low throughout the campaign (SPM < 30 mg l(-1)). Because of rapid flushing times (one or two tides), turbidity tended to mix conservatively between river and coastal waters. Higher coastal turbidity was associated with stronger wind events, and higher fluvial turbidity with spate events. Suspended chlorophyll a levels were usually low throughout the estuary (typically < 2 microg l(-1)) and showed large spatial variability. Because of the rapid flushing of the estuary, it is hypothesised that it was not possible for several algal cell divisions to occur before algae were flushed to the coastal zone. A 'bloom' occurred during the May 1997 survey, when chlorophyll a levels reached 14 microg l(-1). Higher chlorophyll a concentrations at that time occurred at very low salinities, indicating that these waters and algae were largely fluvially derived, and may have resulted from increasing springtime solar irradiation.

Concentrations of suspended particulate organic carbon in the tidal Yorkshire Ouse River and Humber Estuary.

Data are presented for particulate organic carbon (POC) and particulate nitrogen (PN) concentrations in the Humber Estuary and tidal River Ouse Estuary. The POC data were derived from approximately monthly surveys and are consistent with data reported for suspended particulate matter (SPM) in the non-tidal River Ouse (the freshwater river) and with SPM, or bed sediments, in estuarine ecosystems such as the Mississippi, Delaware, San Francisco Bay, Tolo Harbour, the Vellar Estuary and Cochin Backwater, as well as the Loire, Gironde, Ems and Tamar Estuaries. Relative to the dry weight of SPM, the Humber-averaged organic carbon and nitrogen percentages during the year February 1995-March 1996 were 2.6 +/- 0.6% (mean and S.D.) and 0.21 +/- 0.04%, respectively. The ratio of Humber-averaged POC to Humber-averaged PN was 13 +/- 3. Higher POC levels were observed near the Humber's mouth and in the adjacent coastal zone during 'bloom' conditions, and in the upper estuarine reaches during large, winter and springtime freshwater inflows. At these times of high runoff, the POC content of SPM increased progressively up-estuary from the coastal zone to the tidal River Ouse. When inflows became very low, during late spring to early autumn of 1995, both the freshwater-saltwater interface (FSI) and the strengthening turbidity maximum (TM) moved further up-estuary and the POC content of SPM in the upper reaches of the Ouse became lower compared with that immediately down-estuary. This led to a poorly defined POC maximum near the confluence of the Humber, Ouse and Trent, before POC eventually decreased again towards the coastal zone. The lower POC contents in the upper estuarine reaches of the tidal Ouse may have been partly due to POC respiration by heterotrophic bacteria attached to SPM within the TM, consistent with the severe oxygen depletion observed there during high turbidity, summertime spring tides.

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat.

Administration of glucagon to rats at 25 degrees C had no effect upon their VO2, while administration of noradrenaline or noradrenaline plus glucagon raised the VO2. At 5 degrees C, noradrenaline had no effect upon the cold-enhanced VO2, while glucagon caused a rise of 13.7%, implying increased glucagon sensitivity at 5 degrees C. The glucagon-induced enhancement of VO2 was abolished by concurrent administration of noradrenaline.

Adaptive changes in insulin and glucagon secretion during cold acclimation in the rat.

Arginine-stimulated insulin and glucagon outputs from isolated perfused pancreata of warm-acclimated and 2-, 4-, and 6-wk cold-acclimated rats (4 degrees C) were determined to assess whether observed changes in these parameters were a result of cold exposure per se or a part of the adaptive process of cold acclimation. Progressive and sequential changes were seen in both insulin and glucagon outputs. At 2 wk cold acclimation, glucagon rose and insulin output tended to fall, at 4 wk, glucagon output remained elevated and insulin output was further reduced, and at 6 wk, glucagon output had returned to control levels, whereas insulin output was substantially further reduced. These changes resulted in reduction of the insulin-to-glucagon molar ratio of the total arginine-induced output from 7.27 +/- 1.76 (SE) in the warm acclimate to 2.31 +/- 0.79 (SE) at 2 wk, 1.42 +/- 0.29 (SE) at 4 wk, and 1.26 +/- 0.21 (SE) at 6 wk cold acclimation. The data do not provide in vitro support for the hypothesis that changes in pancreatic hormone secretion in vivo are a consequence of cold exposure and not cold acclimation.

Insulin secretion by the perfused pancreas of the cold-acclimated rat.

Rats were acclimated to cold at 4 degrees C for a period of 42 days. Pancreases of normal and cold-acclimated rats were isolated and perfused with a Krebs-Henseleit bicarbonate medium containing dextran, adenosine, glucose, and a fluorocarbon as oxygen carrier. The biphasic secretion pattern of insulin in response to glucose stimulation was evident in both groups. Both basal and glucose-induced insulin release from pancreases of cold-acclimated rats exhibited a very significant reduction in comparison with controls (p less than 0.001). These observations are interpreted as indicating that cold-acclimation, an altered steady state of metabolism, is characterized by enhanced sympathetic activity which reduces insulin availability and release. Consequently enhanced free fatty acid mobilization resulting from reduced inhibition by insulin of lipolysis in the peripheral fat depots and increased lipolysis resulting from sympathetic activation are seen.

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat.

1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption (VO2), lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported. 2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses. 3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of VO2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate. 4. W cells were unresponsive to glucagon in terms of lipolysis and VO2, C cells responded to glucagon with parallel increases in lipolysis rate and VO2. Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells were more sensitive to these agonists than W cells. 5. Lipolysis/VO2 coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms. 6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing VO2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells. 7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased beta-oxidation.

Gastric inhibitory polypeptide and insulin responses to orally administered amino acids in genetically obese hyperglycemic (ob/ob) mice.

The effects of oral administration of eight L-amino acids (alanine, arginine, cysteine, glycine, histidine, hydroxyproline, lysine and threonine) individually or as an amino acid mixture on plasma gastric inhibitory polypeptide (GIP), insulin and glucose concentrations were examined in 18-h fasted obese hyperglycemic (ob/ob) mice. At a dose of 5.4 mmol/kg body weight, arginine, cysteine, histidine and the amino acid mixture were equipotent in terms of increasing plasma GIP and insulin concentrations. Alanine, hydroxyproline and lysine also increased plasma GIP, but insulin concentrations were unchanged. In contrast, threonine failed to affect either GIP or insulin concentrations. There was no correlation between either the incremental or integrated GIP and insulin responses, and none of the amino acids administered affected circulating glucose concentrations. The results indicate that a range of essential and nonessential neutral and basic amino acids stimulate the release of GIP in ob/ob mice. However, GIP made only a modest contribution to the stimulation of insulin secretion following administration of amino acids in the presence of basal glycemia.