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Biomedical subjects

M DiGirolamo

Publications and source records attributed to M DiGirolamo.

70 records · Page 4Linked to original sources

Novel regulation of lipoprotein lipase activity in rat brown adipose tissue: effects of fasting and caloric restriction during refeeding.

We studied the effects of a 3-day fast and 20 days of refeeding on lipoprotein lipase activity (LPL) in the interscapular brown adipose tissue (BAT) of sexually mature male rats. Rats were refed either ad libitum or restricted quantities (75 or 50% of normal ad libitum food intake). BAT-LPL, expressed on a per depot basis, decreased with fasting and returned to control values by day 3 of refeeding ad libitum. In contrast, refeeding restricted quantities for 5 to 20 days limited regain of body weight and increased BAT-LPL significantly above the values observed in rats refed ad libitum. These adaptations in BAT-LPL activity differ markedly from those observed in rat white adipose tissue or heart muscle and may serve to increase the supply of fatty acids from circulating lipoproteins for BAT metabolic needs and maintenance of thermogenesis during undernutrition.

Adipose Tissue, Brown↗

Development and testing of an automated food dispenser for small rodents.

An automated feeder system capable of delivering variable quantities of ground stock diet at predetermined time intervals was developed. The system consisted of feeder units activated by a solenoid connected to a sliding food chamber, a wiring harness, and a control unit. Testing for reproducibility of food delivery indicated reliable and consistent results with a coefficient of variation not exceeding 3% for multiple consecutive deliveries. Field testing in an actual feeding experiment with 35 rats in seven groups showed remarkable adherence to preset conditions. No untoward effects were observed when one group of free-eating, ad libitum fed rats was compared to another group fed unrestricted amounts of feed by the automated feeder. The feeder system was versatile, reliable, and easily adjustable to animal room environments.

Animal Feed↗

Modified subtotal thyroidectomy in the management of Graves' disease.

A prospective study of a new surgical approach (modified subtotal thyroidectomy) in the management of Graves' disease was carried out in 55 patients. The patients were followed over an average of 4 years with a strict protocol involving serial clinical and chemical evaluations (T4, T3RIA, TSH) and yearly thyroid scans. Long-term euthyroidism was achieved in 94% of the patients. These results are markedly superior to the functional results occurring after the standard thyroidectomy in widespread current use. In particular, the development of postoperative hypothyroidism, which is usually manifest by the second year after operation, has not occurred in this series. Observations of TSH elevations in som euthyroid postoperative patients may have important implications regarding the mechanism by which appropriate surgical resection favorably affects the pathophysiology of Graves' disease.

Adolescent↗

Suppression of food intake by adenosine and inosine.

The effect of adenosine and inosine on food consumption was tested by a 4 hr satiety assay in rats fasted overnight who then received injections subcutaneously, and also in ad libitum fed rats infused intravenously for 24 hr periods. It was found that adenosine, and to a lesser degree inosine, produced a significant suppression of food intake (86 and 69% reduction from control, respectively) during the 1st hr after subbcutaneous injection. This effect persisted for 4 hr, at the end of which both substances produced an average 37% reduction in food intake from control values. This effect of adenosine was also found in ad libitum-fed animals infused intravenously with adenosine for 24 hr (35% reduction from control). These studies report a previously undescribed effect of adenosine and add another substance to the list of agents shown to influence food intake regulation. Since adenosine is known to play a local regulatory role on adipose tissue metabolism and is generated and released from adipose tissue, the present findings may indicate an additional role for adenosine in providing a feedback regulatory signal between the adipose organ and the hypothalamic centers of food intake regulation.

Adenosine↗

Glucose metabolism in isolated fat cells: enhanced response of larger adipocytes from older rats to epinephrine and adrenocorticotropin.

The effects of insulin and of two lipolytic hormones (epinephrine and ACTH1) on the rate and pattern of glucose metabolism were compared during incubation of isolated fat cells, obtained from epididymal fat pads of rats of varying age and degrees of adiposity. Glucose metabolism and the intracellular free fatty acid levels were expressed on a per cell basis and in relation to adipocyte size. The data for total glucose metabolism show that, in contrast to the declining insulin effect observed with adipocyte enlargement, the stimulation of glucose uptake and metabolism by these lipolytic hormones was significantly greater in the larger fat cells from the older fatter rats than in the smaller ones from the younger leaner rats. Lipolytic hormones suppressed, whereas insulin enhanced, fatty acid synthesis; moreover the lipolytic hormones stiumlated glucose ce effect of epinephrine on the intracellular free fatty acid levels was greater in the small fat cells than in the large ones; this effect of epinephrine was markedly curtained by the presence of glucose in the incubation medium, making it unlikely that acceleration of glucose metabolism by the lipolytic stimulus was mediated by an elevation of the intracellular free fatty acid level. The present results show a markedly enhanced capacity of the large adipocytes to accelerate glucose metabolism in response to these liplytic hormones. Thus, in contrast to prevailing notions of declining hormonal responsiveness with expanding fat cell size in older and more obese animals, this study documents an instance of increased hormonal response in enlarged adipocytes and points to the need for a more comprehensive reevaluation of the various hormonal effects in adipocytes of different size.

Adipose Tissue↗

Water content of rat adipose tissue and isolated adipocytes in relation to cell size.

Epididymal adipose tissue composition and adipocyte water content were studied in male rats during growth and development of spontaneous obesity. The data show that a highly significant positive correlation exists between fat-cell volume and intracellular water space (IWS) (r=.967, P less than .001). Intracellular water, expressed as picoliters per fat cell, varied from 1.5-2 in small fat cells (mean vol, 30-50 pl) to 9-10 in large cells (800-1,000 pl). When expressed as percent of fat-cell volume, IWS varied from 5-7% in the small fat cells to 1-1.3% in the large ones. Total adipose tissue water continued to increase with increasing adipose mass. Similarly, total adipocyte water increased with enlarging cell size and tissue mass. The contribution of total adipocyte water (as contrasted to that of nonadipocyte water) to total tissue water, however, was found to be limited (less than 23%) and to decline progressively with adipose mass expansion.

Adipose Tissue↗

Remnant function after subtotal thyroidectomy for Graves' disease.

Although it has been thought that future thyroid function after subtotal thyroidectomy for Graves' disease was intimately related to the mass of the thyroid remnant, long-term functional results have not been clearly established. These questions were examined in a retrospective study of 86 surgical cases with histologically confirmed Graves' disease. Operation resulted in euthyroidism in 76% of cases. Recurrent thyrotoxicosis appeared in 8%. Hypothyroidism developed in 14 patients (16%), all with estimated remnant weights of less than 8 gm. In each case, hypothyroidism was diagnosed within the first postoperative year. The capability for early diagnosis of hypothyroidism, however, is a significant advantage of surgical treatment. Within the range of estimated remnant weights, a significant and negative correlation was found between remnant size and the subsequent development of hypothyroidism, but neither euthyroidism nor recurrence of thyrotoxicosis could be correlated with remnant size. In the individual patient, therefore, estimated remnant size is of limited value in predicting future thyroid function.

Adolescent↗

Metabolic patterns and insulin responsiveness of enlarging fat cells.

The rate and pattern of glucose metabolism, basal lipolysis, and intracellular concentration of free fatty acids were determined in isolated epididymal fat cell preparations (mean volume 30-800 pl) from rats on the basis of fat cell number and in relation to the cell volume. The effects of increasing glucose concentrations in the medium and of insulin on the cellular metabolic activities were compared. Expanding fat cell volume correlated positively and significantly (P < 0.001) with the synthesis of glyceride glycerol from glucose (correlation coefficient, r = 0.919), with rates of basal lipolysis (r = 0.663), and with intracellular free fatty acid accumulation (r = 0.796); it correlated negatively and significantly with glucose conversion to glyceride fatty acids (r = -0.814, P < 0.01). The differences in patterns of glucose metabolism and basal lipolysis between small (<100 pl) and large (>400 pl) fat cells were not modified by insulin or by increments in glucose concentration. The results indicate that the reduced capacity of the large fat cells to respond to insulin cannot be attributed solely to a limited capacity of the cells to take up and metabolize increasing amounts of glucose. The acquired unresponsiveness of the large cells to insulin may result from an alteration in the mechanism of action of insulin and may be related to an intracellular metabolic derangement with increased basal lipolysis, free fatty acid accumulation, and accelerated glyceride synthesis resulting from the accumulation of triglyceride.

Adipose Tissue↗

Cellular, metabolic, and clinical consequences of adipose mass enlargement in obesity.

When adipose tissue enlarges in obesity, as the result of an imbalance between caloric intake and caloric expenditure, many changes occur in the cellular components of the adipose mass. A combination of increased cell size and number underlies the accretion of the adipose mass, however, only a reduction in cell size is possible with weight loss. Several metabolic abnormalities accompany obesity--most important--hyperinsulinemia, hyperlipidemia, insulin resistance, and carbohydrate intolerance. Clinical consequences of obesity include hypertension, venous insufficiency, gallbladder disease, osteoarthritis, pulmonary and cardiovascular insufficiency, diabetes, and atherosclerotic cardiovascular disease, and all are dependent on the severity and duration of the obesity. Once established, obesity is difficult to correct because of the development of many adaptive mechanisms by which obesity defends itself.

Adipose Tissue↗