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Biomedical subjects

N Baker

Publications and source records attributed to N Baker.

At least 73 records · Page 4Linked to original sources
PubMed1986

Inhibition of fatty acid incorporation into adipose tissue triglycerides in Ehrlich ascites tumor-bearing mice.

Using a recently developed technique of direct tracer injection into selective adipose tissue sites (Baker et al., Mech. Ageing Dev., 27: 295-313, 1984), we have studied the esterification of free fatty acids (FFA) to triglyceride fatty acids in the epididymal fat pads of normal and Ehrlich ascites carcinoma-bearing mice. We have tested the hypothesis that, during Ehrlich ascites carcinoma growth, a defect develops, resulting in the inhibition of the esterification and incorporation of FFA into adipose tissue diglyceride and triglyceride fatty acids. Our technique allowed the measurement of the disappearance of [1-14C]palmitic acid as FFA and its incorporation into di- and triglyceride fatty acids over 1 h. Multicompartmental analysis was used to compute the fractional rates of esterification and turnover. Using measured FFA pool sizes and assuming near-steady-state conditions, we estimated the transport rates (mass/time) of fatty acid esterification and turnover. Our results indicate that, compared to controls (normal mice), the epididymal fat pads of mice bearing early (5-day) and advanced (9-day) Ehrlich ascites carcinoma, respectively, show: 65% and near complete (congruent to 99%) decreases in the fractional rates of FFA esterification; about 2- and 24-fold increases in the FFA pool sizes; and 40% and 70% decreases in the transport rates of esterification.

Adipose Tissue↗
PubMed1985

An analysis of waiting times in a pediatric emergency department.

Waiting times in a pediatric emergency department were studied using direct observations of patients and health providers on 14 separate days. The mean waiting time (from entry to first physician contact) of the 216 children studied was 49 minutes. Time spent in the waiting room was increased by both the nonavailability of a nurse and the nonavailability of an examining room, and was decreased by the severity of the patient's illness. Time spent in the examination room waiting for the physician was related to the availability of the physician and the number of patients concurrently registered in the emergency department as well as the severity of their complaint. Recommendations for decreasing waiting time, based on the observations, are made. Although each setting is unique, the study provides a model for the analysis of waiting patterns in similar facilities.

Child↗
PubMed1985

In vivo tracer studies of perturbed fatty acid transport and metabolism in adipose tissue.

There is a 'futile' cycle of unknown significance operating at a very rapid rate (about 40 percent that of the total central fat droplet's daily turnover rate) in white adipose tissue of normal mice. The futile cycle may be measured and studied because it occurs in a region of the adipose tissue that has poor anatomical contact with the capillaries coupled with a high affinity of the adipocytes, plasma membranes for the FFA in the ECF. The cycle is drastically inhibited in mice bearing the Ehrlich ascites carcinoma, a transplantable tumor; the inhibition is associated with a 20-fold increase in the FFA pool size of the epididymal fat pad (measured directly) and a 70 percent reduction in the TGFA pool that is involved in the cycle (estimated indirectly from kinetic measurements). However, the mass of TGFA in the central lipid droplet was being conserved in the tumor-bearing mice during this study. The TGFA pool involved in the cycle represents only about 1 percent of the total adipose tissue TGFA. The relation of this futile cycle to adipose TGFA turnover, plasma FFA turnover and oxidation to CO2, dietary sources of TGFA, and the loss (and preservation) of body fat in cancer-bearing animals was considered in terms of a simple model. Although the significance of the altered futile cycle is unknown, the new approach described here, coupled with other quantitative tracer and non-tracer measurements, may prove useful in understanding factors that lead to obesity or body fat loss.

Adipose Tissue↗
PubMed1984

Fatty acid metabolism in adipose tissue of aging mice after direct tracer injection into fat pads.

We have examined previously reported age-related defects in triglyceride synthesis from [1-14C]palmitate in adipose tissue of mice. Three techniques were used: in vitro, using adipocytes isolated from epididymal fat pads of young and old mice; and in vivo, using two new methods to measure free fatty acid (FFA) esterification by adipose tissue (direct injection of labeled palmitate-albumin complexes in large or small volumes into the extracellular spaces of the epididymal or inguinal fat pads of young and old mice). When the entire fat pad was filled with tracer we no longer observed heterogeneous labeling of adipocytes in epididymal fat pads that occurred in an earlier study in which an in vivo-in vitro method has been used. Free fatty acids were converted to triacyglycerol faster by adipocytes of large cells from older animal than by those of small cells from young mice; when the cell sizes of young and old mice were approximately equal, then the rates of FFA esterification were the same in young and old adipocytes. When FFA was injected as a small bolus the fractional rates of FFA disappearance and of FFA incorporation into triacylglycerol in the different fat pads, observed during a 60-min period, were the same (about 5 min or less) regardless of the region of the fat pad studied (distal or proximal epididymal fat pad), the type of fat pad (epididymal or inguinal), or the age of the mice (12-92 weeks). Other potential applications of the direct injection technique for studying FFA metabolism and structure-function in adipose tissue in vivo are discussed. Our findings, coupled with the earlier study in which labeled FFA was added to the outside of fat pads, indicate that, in adipose tissue of old mice, there exist barriers comprising mesothelial cells, collagenous structures, and/or the outer layer of adipocytes in fat pads, that interfere in the transport of FFA to the interior adipocytes when FFA is added outside the fat pad. This age-related defect may be circumvented by injecting tracer directly into the interstitial fluid compartment.

Adipose Tissue↗
PubMed1984

Triacylglycerol secretion in rats: validation of a tracer method employing radioactive glycerol.

A two-compartment model was developed to analyze the temporal changes in plasma triacylglycerol (TG)-specific radioactivity after injection of [2-3H]glycerol into rats. The analysis, which yielded fractional rate constants of TG secretion, was tested in rats fed diets either adequate or deficient in essential fatty acids (EFA) and containing either glucose, fructose or sucrose as the dietary carbohydrate. The method of analysis appeared valid, first, because of a close agreement between experimental and computer-fitted TG-specific radioactivity curves, and second, because the fractional rate constants obtained were quite similar to fractional rate constants determined previously by the Triton WR-1339 technique in rats maintained on identical diets. The results show that EFA deficiency increased the fractional rate constant of TG secretion 1.7-, 1.8- and 3.3-fold and the rate of TG secretion 1.8-, 1.6- and 1.4-fold when the dietary carbohydrate was glucose, sucrose and fructose, respectively, in comparison with control rats fed diets supplying these same carbohydrates but adequate in EFA. In the latter groups, the rates of plasma TG secretion were in the range of 0.14-0.17 mg/min per 100 g body weight, and the rate of secretion in the fructose-fed rats was only 20% higher than in the glucose-fed rats.

Animals↗
PubMed1984

Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor.

We determined the contribution from host hepatic and extrahepatic tissues to newly synthesized fatty acids (FA) in the Ehrlich ascites tumor (EAT). We administered 3H2O (subcutaneously) and [14C]glucose (in a test meal) and measured the appearance of radioactivity in plasma triglyceride fatty acids (TGFA) and free fatty acids (FFA) and in tumor total lipid fatty acids (TLFA). Using [14 C]FFA, we selectively labeled epididymal fat TGFA to estimate the FA transport rate from intraperitoneal adipose tissue directly to the tumor. Contributions of four major pathways to newly synthesized FA in EAT were determined by multicompartmental analysis. De novo FA synthesis by EAT accounted for more than 93% of the TLFA radioactivity found in the tumor. Contributions from liver TGFA via plasma TGFA (less than 0.5%), adipose tissue TGFA via plasma FFA (less than 6%), and adipose tissue TGFA via direct intraperitoneal transport of FFA (less than 1%) accounted for less than 7% of all TLFA radioactivity measured in the EAT. Thus the present study establishes that practically all labeled esterified FA in the EAT is derived from de novo synthesis by tumor cells.

Adipose Tissue↗
PubMed1983

Heterogeneous labeling of adipocytes during in vivo-in vitro incubation of epididymal fat pads of aging mice with [1-14C] palmitate.

We have hypothesized that the in vivo-in vitro technique of Stein and Stein for studying free fatty acid incorporation into adipose tissue triglycerides and phospholipids may introduce artifacts due to diffusion barriers such as collagenous membranes, especially in fat pads of old animals. By using this technique in young and old mice and peeling the external cells, either physically or by collagenase treatment, we were able to show that the outer adipocytes are preferentially labeled. However, this pattern of heterogeneous labeling occurred in fat pads of both young (10-14 weeks) and old (80 weeks) mice. Fat pads are known to develop thicker, collagenous outer membranes during aging. Therefore, it seems likely to us that the marked decrease in free fatty acid esterification in fat pads of old mice, using the in vivo-in vitro method that we have described previously and confirmed here, could have been due to greater diffusion barriers in the tissues of the older mice.

Adipose Tissue↗
PubMed1983

Incomplete free fatty acid oxidation by ascites tumor cells under low oxygen tension.

We tried to understand why our earlier estimates of fatty acid (FA) oxidation rates under the nearly anaerobic state of the Ehrlich ascites tumor (EAT) in vivo were even greater than those found in vitro under aerobic conditions. Using tracers [1-14C]linoleate, [1-14C]-, and [9,10-3H]palmitate, and NaH14CO3, we estimated essential and nonessential FA oxidation rates to CO2 + H2O by EAT in living mice and in vitro under aerobic and anaerobic conditions. Sequestration of intraperitoneally (ip)-injected 14C-FFA allowed a selective labeling of the tumor versus the host; thus, breath 14CO2 could be used to estimate the maximum rate of FA oxidation in vivo by the tumor. Initially, we measured breath 14CO2 following NaH14CO3 injections and developed a multicompartmental model to simulate the tumor-host HCO-3-CO2 system. This model was integrated with our earlier model for tumor FA turnover. The integrated model was fitted to breath 14CO2 data from mice injected ip with 14C-FFA to compute tumor FA oxidation rates. Both essential and nonessential FA were oxidized to CO2 at similar rates. The maximum rate of total FA oxidation to CO2 was 5-6 nmol FA X min-1 X 7-ml tumor-1, about 5-10 times lower than all previous estimates obtained in vitro and in vivo. To resolve this dilemma we used doubly labeled [1-14C; 9,10-3H]palmitate and found that under aerobic conditions, in vitro, EAT formed 3H2O and 14CO2 at nearly equal rates. These rates were suppressed markedly but unequally at low PO2. Anaerobic suppression of 14CO2 formation greatly exceeded that of 3H2O formation. As a result 3H2O/14CO2 reached a value of congruent to 10 at low PO2. Our data indicate that under the nearly anaerobic conditions of a growing EAT in vivo, the partial beta-oxidation of FA to 2C + H2O takes place at a 5 to 10 times faster rate than the complete oxidation of FA to CO2 + H2O. This finding can account for earlier apparent inconsistencies in the literature, since aerobic studies of 14C-FA oxidation to 14CO2 in vitro and of 3H-FA oxidation to 3H2O under nearly anaerobic conditions would both overestimate greatly the rate of FA oxidation to CO2 by EAT in vivo.

Animals↗
PubMed1983

Nascent and remnant lipoprotein turnover in rats: experimental design and simulation.

We have attempted to predict the kinetic behavior of the complex very low-density lipoprotein (VLDL; d less than 1.006) fraction in blood plasma of rats in the steady state. Specifically we proposed a simple model with two different kinds of nascent VLDL particles derived from the liver, one containing apoprotein B (PI/II) [apoB(PI/II)], the high-molecular-weight apoB, and the other, apoprotein B (PIII) [apoB(PIII)], the low-molecular-weight apoB. Two other particles, the corresponding remnants derived from the nascent VLDL particles were also included. Then a number of feasible in vivo tracer experiments were considered in which VLDL labeled in the apoB and/or triglyceride (TG) moieties would be injected into recipient rats and the kinetic behavior of the various compartments predicted by simulation analysis. In addition the kinetic behavior of products such as free fatty acids formed during hydrolysis of labeled TG fatty acids and liver TG derived from labeled circulating remnants was considered. Both the relative sizes of nascent and remnant particles and the extent of average hydrolysis of nascent VLDL-TG (before formation of a remnant particle) were considered in our analysis. On the basis of these predictions we have suggested a number of experimental approaches that should be helpful in defining the relative pool sizes and the turnover rates of each kind of particle in vivo.

Animals↗
PubMed1982

Essential and nonessential fatty acid oxidation in mice bearing Ehrlich ascites carcinoma.

We tested the hypothesis that mobilized (essential) free fatty acids (FFA) are spared from oxidation in cancer-bearing animals. We injected tracers [1-14C] linoleate, [1-14C] palmitate and NaH14CO3 intravenously as single rapid doses in separate groups of mice bearing Ehrlich ascites tumor (EAT) and controls, and measured breath 14CO2. The data from NaH14CO3 injections were used to develop kinetic, compartmental models of the HCO3--CO2 systems. These models were integrated with our earlier model of plasma FFA turnover for control and EAT-bearing mice. The integrated multicompartmental models were then fitted to breath 14CO2 data from mice injected with tracer FFA to compare the rates of FFA oxidation. FFA were not spared from an oxidative fate in our cancer-bearing vs normal animals; moreover, essential FFA were not preferentially spared from oxidation compared to non-essential FFA in the cancer-bearing mice.

Animals↗
PubMed1982

The use of in vivo-in vitro labeling techniques to study phospholipid fatty acid turnover and fatty acid esterification into triglycerides in adipose tissue of aging mice.

We are interested in membrane phospholipid and triglyceride synthesis and turnover in aging cells. As a preliminary, short-term feasibility study we have used an established in vivo-in vitro technique to estimate the initial rates of [1-14C] palmitate (complexed to albumin) esterification to triglycerides and phospholipids in adipocytes and non-adipocytes in the epididymal fat pads of aging mice (8-92 weeks). We have expressed our data in terms of unit cell, unit triglyceride mass and unit (membrane) phospholipid mass. Fat pad and adipocyte size, cell surface area, and adipocyte volume changes were measured and found to follow the same relations as reported in the literature, with some exceptions in very old mice (retired breeders). Rates of fatty acid esterification to triglycerides were about 100 times faster than those to phospholipids in adipocytes. Aging caused a marked fall in the rates of triglyceride fatty acid formation from added palmitate; thus, the rate of fatty acid esterification to triglycerides fell from 0.75 to 0.13 nequiv. fatty acid per min per fat pad (youngest most active group, cf. oldest group). Esterification of fatty acids into phospholipids in adipocytes of the oldest mice was significantly lower than in those of the young and middle-aged groups. Contamination of adipocytes by non-adipocytes was observed in fat pads from old, but not from young, mice. The non-adipocytes accounted for about half of the phospholipid fatty acid esterification. The rate of phospholipid esterification was so slow in adipocytes (all ages) and so relatively fast in non-adipocytes that further studies of phospholipid fatty acid turnover in adipocytes using this system are not considered feasible, especially as a means for studying removal rates of autoxidized fatty acids from membrane phospholipids in vivo during aging.

Adipose Tissue↗
PubMed1981

Hepatic contribution to newly made fatty acids in adipose tissue in rats and inhibition of hepatic and extrahepatic lipogenesis from glucose by dietary corn oil.

We have reexamined an earlier rat study in which the authors concluded that 60 min after [U-14C]-glucose injection half of labeled fatty acids found in adipose tissue had been made in liver and then transported to the adipose tissue. We have shown that even under conditions in which the lipogenic role of the liver is optimized (fed-refed rats on a fat-free, high-carbohydrate diet), almost none of the labeled fatty acids found in adipose tissue of rats 60 min after they were fed a labeled glucose test meal was derived from the liver. This conclusion was based experimentally on (a) the use of the blocking agent Triton WR 1339 to measure the total labeled triglyceride fatty acids (TGFA) synthesized and secreted by the liver in 60 min and (b) comparison of plasma TGFA-14C data with radioactivity found in liver and in adipose tissue in 60 min. Without using Triton WR 1339, mathematical, analysis of plasma TFGA-14C following the glucose test-meal leads one to the same conclusion: 97% of 14C-labeled fatty acids found in adipose tissue at 60 min was made in situ. Additional studies in rats established that the source of error in the earlier studies was an incorrect assumption that dietary corn oil could inhibit hepatic lipogenesis from glucose C without inhibiting fatty acid synthesis in adipose tissue. In our studies, 10% corn oil inhibited equally both hepatic and adipose tissue fatty acid synthesis from glucose C under conditions that precluded any significant transport of labeled TGFA-14C from liver to adipose tissue.

Adipose Tissue↗