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Biomedical subjects

M DiGirolamo

Publications and source records attributed to M DiGirolamo.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lactate production in adipose tissue: a regulated function with extra-adipose implications.

Estimates of the quantitative contribution of adipose tissue to whole-body glucose metabolism, previously reported as 1-3%, have been revised to be on the order of 10-30%. These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2 and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r = 0.89, P less than 0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50-70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review.

Adipose Tissue↗
PubMed1992

Reversal of high-fat diet-induced obesity in female rats.

The purpose of the present study was to test whether the degree of obesity or the duration of the obese state affects the reversibility of diet-induced obesity. This was accomplished by initially feeding adult female Wistar rats either a low-fat diet (Chow) or one of two high-fat diets (HFDs; 30 and 60% of total calories as dietary fat; 30% HFD and 60% HFD, respectively). Fifty-four days, reversal 1 (R1), or ninety-seven days, reversal 2 (R2), later the HFDs were substituted with the low-fat control diet in subgroups of rats. Animals from all groups were sampled at three intervals: the start of R1 (R1 start), and the completion of R1 (R1 end) and R2 (R2 end). At the end of each interval the 60% HFD-fed group had increased body weight, carcass lipid content, and retroperitoneal and parametrial white adipose tissue (RWAT and PWAT) pad weight, fat cell diameter, and fat cell volume, but not fat cell number (FCN), compared with the other groups. The 60% HFD-fed rats also exhibited a marked and persistent hyperphagia that continued even as most of the indexes of obesity approached their maximal values (R1 end). The 60% HFD group had a transient increase in RWAT and PWAT lipoprotein lipase activity that followed the development of most obesity indicators. A clear intermediate level of obesity did not develop in the 30% HFD-fed group. Instead, these animals had nonsignificant increases in these measures of adiposity, making it impossible to test whether the severity of the obesity affected its reversibility in age-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Glucose metabolism in isolated rat adipocytes: estimate of total recovery by the product summation method.

To determine the completeness of glucose recovery into its metabolic products, adipocyte glucose utilization was compared by two different methods in a basal and in an insulin-stimulated metabolic state. One of the methods (product summation) is based on the recovery of (( U-14C ))-labeled glucose in carbon dioxide and triglyceride, together with the assay of lactate and pyruvate released into the medium from the incubated cells. The second method is a modification of a procedure by which the quantity of tritiated water that is released by metabolism from +AD5-3H+BD-labeled glucose is determined. It was found that the results of the two methods were in very close agreement. Neither method measures glucose conversion to glycogen. However, glycogenic activity is very low in adipocytes and represents only a small percentage of utilized glucose. Therefore, the finding of comparable results between the two methods suggests that the summation of the metabolic products carbon dioxide, triglyceride, lactate, and pyruvate does account for nearly all of the glucose utilized. This has important implications for the understanding of the considerable variations in rate and patterns of glucose metabolism by the fat cells under a variety of experimental conditions.

Adipose Tissue↗
PubMed1991

Preferential loss of body fat during starvation in dietary obese rats.

This study was undertaken to examine whether diet-induced obesity alters the amount and/or composition of weight lost during starvation. The amount and composition of weight lost during a 4-day period of starvation was determined before and at 17, 30 and 42 weeks after rats (350 g of body weight) were given a high fat diet (HFD). To control for effects of aging, a second group of rats, fed standard laboratory chow, was also subjected to similar periods of starvation. Although total weight loss during starvation was never greater for HFD rats than for chow-fed rats, the former group showed a clear patter of increasing loss of body fat and total energy and conservation of fat-free tissues with periods of starvation later in life. In addition, chow-fed rats showed substantial energy conservation during each period of starvation (i.e. they lost less energy each day than their pre-starvation energy requirements). In contrast, HFD rats demonstrated substantial energy conservation only at 17 weeks and not at 30 or 42 weeks; during the last period of starvation, their average daily loss of carcass energy exceeded their pre-starvation energy requirements. This suggests the increased fat mass of these rats may have led to increased fuel availability and to an increased metabolic rate during starvation. If these results are applicable to humans, the more obese subjects are likely to show greater total loss of energy than lean subjects, but show a lesser loss of lean body mass, at least initially. If protein requirements are reflected by the ability to mobilize protein during food restriction, protein requirements would be substantially lower in the dietary obese rats than in controls. In summary, diet-induced obesity leads to preferential loss of body fat and conservation of lean mass during starvation.

Adipose Tissue↗
PubMed1991

Effects of blood transfusion on the immune responsiveness and survival of cancer patients: a prospective study.

To evaluate whether blood transfusion exerts an adverse influence on cancer evolution, a prospective clinical and immunologic investigation was carried out on 58 surgical patients with gastric or colorectal adenocarcinoma. None had had previous transfusion; 35 received perioperative transfusion. Among preoperative variables, only red cell count and hemoglobin concentration were significantly reduced in the patients transfused at operation. Other clinical characteristics and immunologic functions (except interferon-gamma release) did not differ significantly from those of untransfused patients. The survival rate of transfused patients, although shorter, was not significantly different from that of untransfused patients. Immunologic tests done after surgery on 30 patients (17 transfused and 13 untransfused) did not show significant differences in the two groups. Significant increases in interleukin-2-stimulated production and immunoglobulin M synthesis were observed in transfused patients after surgery. Patients transfused perioperatively with more than 3 units of blood had some evidence of decreased immune function, but differences were not significant. While shorter survival and some immunologic changes may correlate with the number of transfusions, more patients must be studied to determine whether this relationship will be confirmed.

Blood Transfusion↗
PubMed1991

Collagen production in fasted and food-restricted rats: response to duration and severity of food deprivation.

Malnutrition is associated with defects in connective tissue metabolism such as altered growth and wound healing. Because collagen is the major protein in most tissues, we determined the threshold for induction of altered collagen production by partial food restriction in rats. Groups of animals were fasted 2 or 4 d or were fed 20-100% of a predetermined food intake for 4 to 8 d. Collagen and noncollagen protein production in articular cartilage were determined using purified collagenase digestion of collagen labeled for 2 h in vitro with [3H]proline. Significant decreases in collagen (P less than 0.01) were seen in rats after 4 d of 40% (weight-losing rats) or after 8 days of 80% (weight-gaining rats) ad libitum intake. Collagen production decreased with both duration and degree of food deprivation; after 8 d of 20% intake, collagen was less than 10% that of controls fed ad libitum (P less than 0.001). In contrast, noncollagen protein production was significantly decreased only after 4 or 8 d of less than 40% intake (weight-losing rats). Maximum suppression of noncollagen protein was to approximately 65% of levels in controls fed ad libitum (P less than 0.01) and was not further reduced in fasted rats. Insulin-like growth factor-I levels were significantly decreased with duration and severity of diet in parallel with changes in collagen. The degree and sensitivity of altered collagen production to small changes in food intake suggest close regulation of this peptide and a potential role for decreased collagen synthesis in connective tissues during mild states of undernutrition.

Animals↗
PubMed1991

Energetic and metabolic studies of intragastric infusion of calories before and after exercise training.

The technique of intragastric infusion of calories was used to examine the energetics and metabolic response to fasting, feeding and overfeeding states in adult, sedentary subjects. All subjects were studied before and after participating in a 12-week aerobic exercise training program that increased maximum aerobic capacity by an average of 15.6 percent. Body weight did not change during the exercise program, but there was a slight and statistically significant increase in fat-free mass and a significant decrease in fat mass. The exercise program did not affect food intake (as determined from food records). When subjects were studied before exercise training, there was no increase in energy expenditure above fasting levels during continuous infusion of calories at a rate near the subject's maintenance energy requirements. When infusion rate was increased to twice maintenance, energy expenditure increased significantly and produced a measurable thermic effect of food. The changes in glucose, insulin and free fatty acids did not parallel the changes in energy expenditure, but changes in lactate levels did. Moreover, there were some gender differences in the pattern of substrate and hormone changes with changes in feeding state. Exercise training did not alter either energy expenditure or the pattern of changes in substrates and hormones with changes in feeding state. In summary, the exercise program led to changes in body composition without measurable changes in either food intake (assessed from diet records) or energy expenditure (assessed during fasting and continuous infusion of calories). The change in body composition must have been due to either (1) the energy cost of the exercise itself, or (2) changes in the substrates used for oxidation, either during or following exercise bouts. We conclude that exercise, unlike food restriction, can lead to changes in body composition without altering body weight or metabolic rate, and can contribute to the acquisition and maintenance of a desirable body weight and composition.

Adipose Tissue↗
PubMed1990

Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations.

Research efforts investigating the pathophysiology of adipose tissue have often focused separately on either the metabolic or cardiovascular components of an expanding fat mass. However, the growth and development of the fat cells and their vasculature are closely interrelated, a fact that has been established through more than a century of diverse studies of adipose tissue. Recently, the prevalence of obesity in the United States has stimulated investigations into the cardiovascular and metabolic correlates occurring with excessive lipid deposition and subsequent adipose tissue expansion. These investigations have resulted in conclusive evidence that, from a cardiovascular perspective, obesity results in an elevated blood volume and cardiac output, accompanied by an expansion of adipose water space, whereas from a metabolic aspect, the disease is characterized by adipocyte enlargement and associated alterations in metabolic pathways and hormonal responsiveness. Because these separate areas of research have independently shown interdepot differences in perfusion requirements and metabolic adaptations during the transition from the lean to obese state, adipocyte expansion may be partially dependent on the pattern of vascularity. This hypothesis is discussed by examining the integral relationship between the cardiovascular system and adipocyte metabolism, hopefully providing new insight into control of the pathophysiological processes of an expanding adipose organ.

Adipose Tissue↗
PubMed1990

Carbohydrate tolerance improves with fasting in obese subjects with noninsulin-dependent (type II) diabetes.

To determine the effects of short-term fasting on carbohydrate tolerance, 10 obese women with noninsulin-dependent diabetes mellitus (NIDDM) were studied with meal tolerance tests before and after 3 days of fasting. After 3 days' fast, basal serum glucose declined from 15.2 +/- 0.9 to 7.5 +/- 0.7 mmol/L (273 +/- 17 to 135 +/- 13 mg/dL) (mean +/- SEM, p less than 0.001) and the glycemic response to the test meal (area under the glucose curve) improved by 31%. There were no changes in basal or postprandial insulin levels but a slight increase in serum c-peptide. Resting metabolic rate and the thermic effect of food were unchanged. There was a slight but insignificant change in basal and postprandial free fatty acid levels and a significant elevation of basal beta-hydroxybutyrate levels. Blood lactate rose significantly (from 0.9 to 2.0 mM) during the initial meal tolerance test, but no rise in lactate was seen in the meal tolerance test after fasting. Two subgroups of patients were identified based on the degree of glycemic improvement after short-term fasting. Those with lesser improvement in serum glucose showed overnight rises in serum glucose during the period of fasting (the dawn phenomenon), while those patients who normalized serum glucose showed a steady fall in serum glucose. This finding may help to predict the glycemic response to long-term calorie restriction. Carbohydrate tolerance improves in obese diabetic (NIDDM) women after 3 days of fasting, in contrast to the impairment of glucose tolerance seen in lean or obese nondiabetic subjects after fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Adipocyte lactate production remains elevated during refeeding after fasting.

The metabolic state occurring with refeeding after fasting is characterized by the rapid restoration of hepatic glycogen. Recent evidence suggests that a main substrate for glycogenesis is lactate. Because adipose tissue is an active site of lactate production that increases with fasting, we examined the magnitude and duration of lactate production by isolated adipocytes from three adipose depots of rats fasted for 48 h and then refed for up to 96 h. The data show that 48 h of fasting results in a markedly elevated rate of adipocyte lactate production, which increased from 3-9% of total glucose metabolized in the fed state to 49-60% in the fasted state. During the refeeding period, lactate production remained elevated for 12-24 h and then declined. Mesenteric adipocytes had a higher rate and more prolonged elevation in lactate production than cells from the other two depots. We conclude that, with refeeding after a fast, adipocyte glucose conversion to lactate remains elevated during the time of hepatic glycogen restoration. This suggests that adipose tissue may actively produce lactate for glycogenesis during refeeding.

Adipose Tissue↗
PubMed1990

Model of spontaneous obesity in aging male Wistar rats.

We analyzed retrospectively data from 148 chow-fed male Wistar rats killed between the age of 6 wk and 2 yr while varying in body weight from 136 to 917 g. The purpose of this study was to clarify the relationship of body weight and body lipid content with the composition and cellularity of the epididymal and retroperitoneal fat depots. A positive linear association was found between body weight and body water or fat-free dry residue, whereas total body lipid exhibited a curvilinear relationship with body weight. The weight of the epididymal pads was linearly related to body weight but not to body lipid. In contrast, retroperitoneal pad weight was exponentially related to body weight and paralleled total body lipid. A strong linear correlation was found between total body lipid and weight (r = 0.959) or depot lipid content (r = 0.967) of the retroperitoneal fat pads. In this rat model of aging and spontaneous obesity, significant regional differences exist in adipose depot composition and cellularity. A practical outcome of this study is a simple and accurate prediction of body lipid content from the gravimetric determination of the retroperitoneal fat depots.

Adipose Tissue↗
PubMed1990

Electronic determination of size and number in isolated unfixed adipocyte populations.

Adipose tissue cellularity and metabolism are traditionally expressed in terms of mean cell size and number. The need for a simple method allowing rapid determination of cell size and number of freshly isolated, unfixed adipocyte preparations led us to compare estimates of cell size determined by the established method of optical sizing to a proposed method of electronic cell sizing and counting. In collagenase-isolated, unfixed adipocytes whose mean diameters ranged from approximately 40 to 65 microns (obtained from healthy rats weighing 100-360 g) the electronic method provided estimates of the mean cell diameter and size distribution that did not differ from the optical sizing technique. Estimates of mean cell diameter and cell number by the electronic method were rapid and reproducible (coefficients of variation 0.5 and 3.8%, respectively) and a less than 20 sec delay until sample analysis, after mixing of the adipocyte suspension, did not alter these estimates. Electronic determination of cell size and number, using freshly isolated, unfixed rat adipocyte populations (mean cell diameter less than or equal to 60 microns), is rapid and reliable. It will be particularly useful for studies of hormone binding and transport processes where it may be necessary to tightly control cell density.

Adipose Tissue↗
PubMed1990

Prediction of glucose response to weight loss in patients with non-insulin-dependent diabetes mellitus.

Although diet therapy is considered the cornerstone of therapy for obese patients with non-insulin-dependent diabetes mellitus, losing weight is often difficult, and the plasma glucose concentration does not always improve after weight loss. We looked for predictors of improvement in plasma glucose levels after weight loss in 135 obese patients with non-insulin-dependent diabetes mellitus who had lost at least 9.1 kg of body weight. After weight loss there was a bimodal distribution of plasma glucose levels, allowing us to identify patients as "responders" or "nonresponders" according to whether a random plasma glucose level was above or below 10.0 mmol/L after a 9.1-kg weight loss. Fifty-five (41%) of 135 patients were responders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 7.0 +/- 0.2 mmol/L). Many responders had improved plasma glucose levels after only slight weight loss. Eighty (59%) of 135 patients were nonresponders (after a 9.1-kg weight loss, the mean +/- SEM plasma glucose level was 18.3 +/- 0.6 mmol/L). Although the responder and nonresponder groups were comparable in age, sex distribution, plasma glucose levels, and body weight at initial presentation, improvement in the plasma glucose level after weight loss could be predicted by a plasma glucose level of 10.0 mmol/L or lower after 2.3-kg (62% positive predictive value) and 4.5-kg (79% positive predictive value) weight loss. We conclude that, in contrast to conventional teaching, many patients with non-insulin-dependent diabetes mellitus will not have any improvement in plasma glucose levels after a 9.1-kg weight loss. However, a substantial minority (approximately 40%) of obese patients with non-insulin-dependent diabetes mellitus have much lower plasma glucose levels with a weight loss of 9.1 kg or less. Although the plasma glucose response to weight loss cannot be forecast by initial clinical parameters, the success or failure of diet therapy can be predicted from the plasma glucose level after a weight loss of only 2.3 to 4.5 kg. Mild or moderately obese patients with non-insulin-dependent diabetes mellitus who remain hyperglycemic after a weight loss of 2.3 to 9.1 kg are unlikely to improve with further weight loss and should be considered for treatment with insulin or oral hypoglycemic agents.

Blood Glucose↗
PubMed1989

Insulin-stimulated hexose transport and glucose oxidation in rat adipocytes is inhibited by sphingosine at a step after insulin binding.

Spingosine, a naturally occurring inhibitor of protein kinase C, has recently been shown to have potent bioregulatory effects on a variety of cellular processes involving signal transduction mechanisms. In the present studies, we have investigated its effects on activation by insulin of hexose transport and glucose oxidation in isolated rat adipocytes. Preincubation of cells with this long-chain base blocked both the marked activation of these processes by insulin and the smaller activation by phorbol myristate acetate. Inhibition of both insulin and phorbol 12-myristate 13-acetate activation showed the same sphingosine concentration dependence, suggesting a common locus of action. The effectiveness of sphingosine was inversely proportional to the lipid content in the incubation (which was a function of both the age of the animal and the number of cells used) presumably due to dilution of the lipophilic long-chain base into the cellular triglycerides. Sphingosine did not affect either insulin binding to its receptor or the half-maximal concentration of the hormone required to activate hexose transport, but reduced the maximal responses. Thus, the inhibition was at a step distal to the binding of insulin to its receptor. Basal transport activity was not inhibited, suggesting a locus of action prior to the glucose transporter. The inhibitor was also effective when added following activation by insulin of hexose transport and resulted in a rapid reversal of activation (t 1/2 for inhibition was 2-4 min.). Sphingosine and its analogs showed a parallel potency for inhibition both of isolated protein kinase C and of insulin activation in adipocytes, consistent with an essential role for protein kinase C in the activation of hexose transport by insulin.

Adipose Tissue↗
PubMed1989

Creation of a regional medical-nutrition education network.

The Southeastern Regional Medical-Nutrition Education Network (SER-MEN) was developed to coordinate and improve nutrition education in a consortium of the medical schools in Alabama, Florida, Georgia, and South Carolina. SERMEN's central office is at the Medical College of Georgia with the testing office at the University of Alabama at Birmingham. Students, faculty, and consultants in nutrition, education, and computer networking work together on projects on each campus that are coordinated and planned through semiannual meetings. A standardized examination was developed with the Nutrition Test-Item Bank to assess nutrition knowledge at various years of medical students from network schools. Each SERMEN school is connected to a microcomputer system at the central office that provides access to a data base of nutrition education and resources on each campus for developing curricula and syllabi. Funding has been provided by societies, foundations, and government agencies.

Computer Communication Networks↗
PubMed1989

Effects of streptozocin-induced diabetes on glucose metabolism and lactate release by isolated fat cells from young lean and older, moderately obese rats.

Streptozocin-induced diabetes (STZ-D) was produced in male Wistar rats at two stages of development: young, lean rats, weighing 150-220 g (6-8 wk), and older, moderately obese rats, weighing 450-500 g (6-8 mo). A comparable degree of hyperglycemia (420-500 mg/dl) without ketosis was generated by injection of 50 mg/kg i.v. STZ for young, lean rats and 30 mg/kg i.v. for older, fatter rats. The animals were killed 8-11 days after injection. Insulin binding by the isolated adipocytes of both groups was not significantly altered on a per-cell basis by the presence of diabetes. Total adipocyte glucose metabolism, both basal and insulin stimulated, was reduced (63 and 88%, respectively) by the induction of diabetes in young, lean rats. In contrast, the induction of diabetes in the older, moderately obese rats had no suppressive effect on total glucose metabolism by their fat cells. Diabetes increased the relative conversion of glucose to lactate by fat cells from both groups of rats, but in absolute terms, the fat cells from the obese diabetic rats produced significantly more lactate from glucose than cells from the lean diabetic rats, both in the absence and presence of insulin. Diabetes did not alter the glucose concentration at which peak insulin response occurred in either group. We conclude that STZ-D in rats, at different stages of development and degrees of adiposity, results in quantitatively different alterations of adipocyte metabolism, which appear to be postreceptor in nature and result in an increase in glucose conversion to lactate.

Adipose Tissue↗
PubMed1988

Cross-sectional study of nutrition knowledge and attitudes of medical students at three points in their medical training at 11 southeastern medical schools.

Eleven southeastern medical schools cooperated to evaluate nutrition knowledge and attitudes of medical students. This study complements previous reports of an examination of entering freshmen and seniors. Average knowledge scores for 165 students tested after basic sciences (preclinical) training in this study were 67 +/- 7% compared with 53 +/- 6% for freshmen and 69 +/- 8% for seniors. The upperclassmen's scores were higher than the freshmen's (p less than 0.001) and varied with the amount of required nutrition teaching. Only 13% of preclinical students perceived nutrition as important to their careers compared with 74% of entering and 59% of graduating students, suggesting that preclinical teaching reduces their sense of relevance of nutrition to medicine. These findings suggest that nutrition knowledge can be increased through preclinical coursework and that the knowledge level can be maintained through the clinical years. However, the positive attitude of freshmen toward nutrition is lost after preclinical training and is only partially regained after the clinical years.

Attitude of Health Personnel↗