Biomedical subjects

M DiGirolamo

Publications and source records attributed to M DiGirolamo.

At least 55 records · Page 3Linked to original sources

PubMed1988

Regional differences in adipocyte lactate production from glucose.

Having shown that lactate is an important product of glucose metabolism by rat epididymal adipocytes, we investigated possible regional differences in adipocyte lactate production and the role of the animals' nutritional state and stage of development. [U-14C]glucose metabolism, lactate production, and response to insulin were measured in fat cells isolated from four adipose regions (subcutaneous, epididymal, retroperitoneal, and mesenteric) from young lean and older fatter rats, killed either in the fed state or after fasting for 48 h. In the absence of insulin, mesenteric fat cells from either age group metabolized significantly more glucose per cell and converted more glucose to lactate than cells from other depots, regardless of nutritional state. Adipocytes from fasted lean rats showed a significant increase (approximately 30%) in the relative glucose conversion to lactate in all depots when compared with cells from fed lean rats. Fasting of older fatter rats, however, had limited effects on the relative adipocyte glucose conversion to lactate since lactate production was already high (40-50% of glucose metabolized). Mesenteric fat cells had the lowest relative response to insulin, possibly due to the high basal rate of glucose metabolism. These findings indicate that differences exist among adipose regions in the rates of glucose metabolism, lactate production and response to insulin. The anatomical location of the mesenteric adipose depot, coupled with a high metabolic rate and blood perfusion, suggests that mesenteric adipocytes may provide a unique and more direct contribution of metabolic substrates for hepatic metabolism than adipocytes from other depots.

Adipose Tissue↗

PubMed1987

Energy expenditure during continuous intragastric infusion of fuel.

Influence of intragastric formula infusion rate on resting thermogenesis was evaluated in 24 healthy subjects. Metabolic rate (M) was measured by indirect calorimetry following an overnight fast. Subgroups then received a continuous intragastric infusion of a formula diet at three levels: submaintenance (mean +/- SEM, 1.02 +/- 0.04 times fasting M, n = 6), maintenance (1.39 +/- 0.01 times fasting M, n = 20), or supramaintenance (2.77 +/- 0.2 times fasting M, n = 14). Formula inflow was started in the evening, and intraprandial M was measured throughout the following day. Relative to fasting, submaintenance and maintenance infusions produced no detectable change in M. With supramaintenance infusion, M increased significantly (10.1%, p less than 0.05) above fasting level. Hence during continuous formula infusion a rise in M above fasting occurs only when rate of energy infusion exceeds rate of thermal energy losses. These results have implications in regard to energetic efficiency of continuous fuel infusion relative to intermittent food or formula ingestion.

Adult↗

PubMed1987

Effects of food restriction on lactate production from glucose by rat adipocytes.

We investigated the effects of acute food deprivation on the rates of glucose metabolism and lactate production by epididymal fat cells isolated from 2- and 8-mo-old Wistar rats in one of three nutritional states: fed ad libitum, restricted to 50% of ad libitum, or fasted for 48 h. Food restriction did not affect total rates of basal glucose metabolism but significantly altered its pattern. In small fat cells from 2-mo-old rats, donor's food restriction led to decreased basal and insulin-stimulated glucose oxidation and fatty acid synthesis but led to increased lactate production, which increased from 4% of total glucose metabolized by cells from fed rats to 62% by cells from fasted rats. In large fat cells from 8-mo-old rats, donor's food restriction produced minimal changes in basal glucose metabolism and lactate production (already elevated at 37% of total) but caused insulin-stimulated lactate production to increase. These findings indicate that adipose tissue can produce significant amounts of lactate (with adipocyte enlargement and/or food deprivation) and may play an important role in extrahepatic generation of triose intermediates and in the Cori cycle.

Adipose Tissue↗

PubMed1986

Lipoprotein lipase secretion from isolated rat fat cells of different size.

Lipoprotein lipase(LPL) release from isolated small fat cells from young rats and large fat cells from older, fatter rats was compared during in vitro incubation at 30 degrees C. Although large fat cells had nearly three times higher cellular LPL activity, they secreted similar amounts of LPL activity into the incubation medium under both basal conditions (Krebs Ringer bicarbonate buffer containing 4% albumin and 6mM glucose) and after stimulation of LPL release by 5% human serum, or serum plus 1 U/ml heparin. These data suggest that previous observations of an altered tissue distribution of LPL in adipose tissue containing large fat cells can be at least in part explained by an alteration at the level of LPL secretion.

Adipose Tissue↗

PubMed1986

Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes.

Binding of human GH (hGH) and insulin-like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24 degrees C was reached at 120 min and half-maximal specific binding at 6-8 ng/ml. Apparent Ka was 2.1 X 10(9) M-1 and Bmax 7.3 X 10(-11) M/10(6) cells. The human fat cell growth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated. Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species.

Adipose Tissue↗

PubMed1986

Energy utilization in food-restricted female rats.

We studied changes in energy utilization in mature female rats exposed to varying degrees of food restriction. Food-restricted rats showed considerable energy conservation, exhibited primarily as a reduction in the energy required for daily maintenance. When a given body weight loss was produced by starvation (3 or 6 d), changes in body composition and energy utilization differed only slightly (and temporarily) compared with the same body weight lost by partial food restriction. All food-restricted groups demonstrated a remarkable ability to reduce maintenance energy costs and to achieve zero energy balance at food intakes 40-50% of controls. By contrasting these results with our previous work in food-restricted male rats, we identified possible gender differences in the response to food restriction. Females appear to preserve lean mass to a greater degree than male rats by utilizing relatively more fat for energy needs. This preference for fat as a fuel during negative energy balance suggests that females would lose less body weight for a given reduction in carcass energy than males, since fat is calorically denser than lean mass.

Adipose Tissue↗

PubMed1986

Effects of glucose, insulin and epinephrine on lactate metabolism by isolated adipocytes.

Epididymal fat cells were incubated in vitro with either 2 mM or 6 mM [U-14C]lactate, and where appropriate, 6 mM glucose, 10 mU/ml insulin or 2 micrograms/ml epinephrine. Increasing lactate concentration promoted lactate carbon incorporation into specific products, and the presence of glucose significantly enhanced this effect. Significant lipogenic or lipolytic hormonal effects upon lactate metabolism were observed only in the presence of glucose, as insulin primarily increased lactate conversion to fatty acids while epinephrine promoted lactate oxidation. These data emphasize the importance of lactate as an alternative substrate for intermediary metabolism in adipocytes, and indicate that hormonal modulation of lactate metabolism is modest, but distinct, and requires the presence of physiological glucose concentrations.

Adipose Tissue↗

PubMed1985

A new approach for studying the thermic response to dietary fuels.

We describe a new method of studying the thermic response to dietary fuels that involves continuous infusion of a liquid formula diet through a thin nasogastric tube. The data show that the steady inflow of dietary fuel is accompanied by a relatively constant level of energy expenditure, the magnitude of which depends on the rate of fuel inflow. An increase in the rate of fuel infusion above that required for caloric maintenance leads to a rise in energy expenditure. We also give examples, based on preliminary observations, of how the technique can be used to more precisely quantify energy metabolism. The technique may prove useful in the studying efficiency of energy utilization and in examining the extent to which individuals differ in energy efficiency.

Adult↗

PubMed1985

Changes in growth hormone binding and metabolic effects of growth hormone in rat adipocytes following hypophysectomy.

Growth hormone (GH) binding and the effect of GH and insulin on glucose metabolism in rat adipocytes were studied at various time periods following hypophysectomy. Male rats were hypophysectomized at 33-34 days of age. After 6 h, 20 h or 3, 7 and 14 days adipocytes were prepared from epididymal fat pads by mild collagenase digestion (0.5 mg X ml-1, 60 min, 37 degrees C). Glucose metabolism was studied by determining the production of CO2 from [14C]glucose and the incorporation of [14C]glucose into lipids. GH binding was measured in cell aliquots using [125I]hGH. No difference in GH binding to adipocytes was observed between control rats and rats hypophysectomized or sham-operated 6 h earlier. GH binding was significantly decreased 20 h after hypophysectomy and declined further with time after hypophysectomy. Adipose tissue from normal rats is usually refractory to the insulin-like effect of GH. Adipocytes isolated from normal rats were, however, usually responsive to GH immediately after cell isolation, suggesting that refractoriness to the insulin-like effect of GH was lost during the time required for the preparation of adipocytes. The magnitude of the response to GH in adipocytes progressively declined with time after hypophysectomy. The decreased responsiveness to GH with time after hypophysectomy parallelled the decrease in GH binding. The results suggest that the pituitary, directly or indirectly, is necessary for the maintenance of GH binding sites in adipose tissue and that these binding sites are related to the insulin-like effect of GH.

Adipose Tissue↗

PubMed1985

Thermic effect of food after ingested versus tube-delivered meals.

We compared, in six subjects, the thermic effect of food (TEF) after the ingestion of a test meal with that observed after the delivery of an equivalent test meal directly into the stomach through a nasogastric tube. TEF was measured after each test meal (i.e., ingested or tube delivered) until postprandial metabolic rate was not different from fasting metabolic rate (as measured at approximately the same time of day on a previous day). TEF after the tube-delivered meal was not significantly different in magnitude or duration from TEF after the ingested meal. The two types of meals also resulted in similar changes in respiratory quotient. These results suggest that the majority of TEF arises after the food reaches the stomach and that very little of TEF is produced by sensory factors or by the mechanical aspects of eating.

Adult↗

PubMed1985

Effects of variable caloric restriction on utilization of ingested energy in rats.

Body weight reductions were produced in five groups of male Wistar rats (325 g) by starvation or by variable degrees of underfeeding. The resulting body weights were maintained, by adjusting daily food intake, at constant levels for at least 18 days. We found that 1) energy conservation (i.e., a reduction in the amount of energy required for maintenance) developed in proportion to reduction in body weight, 2) energy conservation increased even while reduced body weights were maintained at constant levels, 3) reduction in the energy required for maintenance was largely due to reduced resting metabolic rate, 4) a maximal ability to conserve energy seemed to occur in severely food-restricted rats, and 5) the magnitude of energy conservation appeared to be proportional to the absolute reduction in body weight and was unrelated (in the long run) to rapidity of weight loss. This study confirms that precise mechanisms of energy conservation are set in motion by food restriction and attempts to identify some components of this adaptive response.

Adipose Tissue, Brown↗

PubMed1985

Observations on the course of untreated primary hyperparathyroidism.

Controversy has arisen regarding the indications for elective surgical intervention in asymptomatic primary hyperparathyroidism (HPT). The present study was designed to answer two questions: Is untreated primary HPT a progressive disease over time? If not, are the risks attendant on long-term conservative management comparable to those obtained from surgery? Forty-seven patients with primary HPT, established by a persistently elevated serum calcium level and an inappropriately elevated parathormone value, who were managed conservatively and followed for a minimum of 5 years were identified. Serial data collection included calcium, phosphorus, albumin, creatinine, alkaline phosphatase, parathormone levels, skeletal x-ray films, and complications known to result from primary HPT. For each patient the collected data were divided into three equal periods of time (minimum of 20 months per period). In addition, the patients were classified into three groups based on their average serum calcium levels during the first observation period. No patient in any of the three groups experienced a significant progressive increase in serum calcium levels during the periods of observation. Sixteen of the 47 untreated patients (34%) experienced a complication usually associated with primary HPT: peptic ulcer disease (eight patients), decrease in renal function (five patients), renal calculus (one patient), hypercalcemic crisis (one patient), and ventricular conduction defect (one patient). Four deaths were attributed to these complications. In conclusion, the course of primary HPT and attendant complicating features are not accompanied by worsening of the hypercalcemia initially observed. None of the parameters studied offered an accurate prediction of likelihood, progression, or severity of complications. The risks associated with long-term nonoperative management of asymptomatic primary HPT are nevertheless considerable and exceed the morbidity and mortality rates resulting from neck exploration.

Aged↗

PubMed1984

Meal size and thermic response to food in male subjects as a function of maximum aerobic capacity.

The relationship between size of a mixed, liquid meal and the thermic effect of food (TEF) was studied in two groups of nonobese male subjects differing in maximum aerobic capacity (VO2 max). A design using repeated measures was chosen in which each subject received each meal (water, 500 kcal, 1000 kcal, 1500 kcal) on a different morning. TEF was measured by indirect calorimetry for three hours following each meal and was found to increase systematically, in a nonlinear fashion, as meal size was increased. Subjects with a high VO2 max responded to the two higher calorie meals with a greater TEF than did subjects with a low VO2 max. They also showed a greater increase in TEF for any given increase in meal size. This study establishes a precise relationship between meal size and the thermic effect of food. It also identifies an important variable, VO2 max, in determination of the individual thermic response to food. These findings suggest that individuals with a high VO2 max (such as aerobically trained athletes) show a greater caloric expenditure after eating, particularly after a large meal, than do individuals with a low VO2 max. A high thermic response to food could be beneficial in body weight homeostasis.

Adolescent↗

PubMed1984

Effects of fasting and restricted refeeding on utilization of ingested energy in rats.

Ingested metabolizable energy was partitioned into 3 components--storage, cost of storage, and maintenance--to study energy utilization during 20 days of refeeding following a 3-day fast in adult male Wistar rats. During the refeeding period, one experimental group was refed ad libitum, whereas two others were restricted to approximately 75 and 50%, respectively, of prefast food intake. Energy utilization in the experimental groups was compared with that in nonfasted controls. Energy conservation occurred in all experimental groups during refeeding, and the primary form of that conservation was a decrease in the energy required for maintenance. The decreased requirement for maintenance allowed a greater proportion of ingested energy to be used for restoration of carcass energy. The degree of energy conservation was, in general, proportional to the degree of food restriction during refeeding.

Adipose Tissue↗

PubMed1983

Effects of a high-fat diet on energy intake and expenditure in rats.

The effects of a high-fat diet supplying a constant energy/protein ratio, with and without overeating, on energy intake and expenditure was studied in mature male rats. A control group (LF) received ad libitum access to a low-fat diet. Body weight gain, efficiency of food utilization, and dietary-induced thermogenesis were increased relative to controls in a group with ad libitum access to the high-fat diet (HF-A), but not in a group which was pair fed the diet (HF-P) in amounts (kcal) equal to that of LF animals. However, the individual variability within the HF-A group was high for each measure. An arbitrary separation of that group into 2 subgroups (based on high vs low weight gain) produced one subgroup with increased efficiency, greater weight gain and no change in dietary-induced thermogenesis (HF-AH), and another with no difference in efficiency or in weight gain from the LF group but which had higher dietary-induced thermogenesis (HF-AL). Food intake was slightly, but not significantly, greater for the HF-AH subgroup than for the HF-AL subgroup. We conclude that rats can increase thermogenesis in response to overeating but that the increase is highly variable. The thermogenic response appears to be related to the overeating rather than to the fat content of the diet.

Adipose Tissue↗

PubMed1983

Influence of ambient glucose and insulin concentrations on adipocyte insulin binding.

To elucidate factors of importance for insulin binding, fat cells from humans and rats were incubated under various experimental conditions for different periods of time. Human adipocytes incubated for 24 hours in the absence of insulin showed no significant difference in insulin binding compared with cells from freshly excised tissue. After 48 hours, however, an increased rate of binding (average 54%; P less than 0.05) was obtained. The addition of insulin (2000 microU/ml) to the culture medium resulted in a decrease in insulin binding (average 33%; P less than 0.05) compared with cells maintained in the absence of insulin. There was no apparent difference in receptor affinity, indicating that the altered binding was due to a change in receptor number. In the absence of insulin, elevating the glucose concentration of the medium from 0.8 mM to 22.4 mM did not significantly influence insulin binding. Rat adipocytes showed similar but more rapid changes. Thus, incubation for 24 hours without insulin caused an increase in insulin binding (average 37%; P less than 0.05). This up-regulation was seen even in a high glucose concentration (28 mM) but was completely prevented by the presence of insulin in the medium. Furthermore, when rat adipocytes were incubated with insulin in the presence of a high glucose concentration (28 mM) there was a significant further decrease in insulin binding compared with that of parallel incubations performed in 5.6 mM glucose. Thus, even in the absence of TRIS buffer, insulin-dependent regulation of the number of binding sites is shown for both human and rat adipocyte tissue in vitro. Although this perturbation could be directly due to hormone-receptor interaction at the membrane level, the finding of rat adipocytes that the ambient glucose concentration can modulate this effect suggests the importance of post-receptor events.

Adipose Tissue↗

PubMed1983

Lactate release from isolated rat adipocytes: influence of cell size, glucose concentration, insulin and epinephrine.

Release of lactate was studied during in vitro incubations with isolated fat cells. Lactate release increased (approximately 3-fold) with increasing medium glucose concentration (from 3 to 12 mM) in both large and small fat cells. Large fat cells from older, fatter rats, however, released 3-4 times more lactate per cell than small fat cells from young rats when incubated with 3, 6 or 12 mM glucose. Insulin and epinephrine produced a marked stimulation of lactate release in small fat cells, but these hormones had no effect in large fat cells. Lactate accounted for only 10-15% of the glucose metabolized by small fat cells under all incubation conditions but was nearly 40% of glucose utilized by large fat cells at glucose concentrations greater than 6 mM. In conclusion, lactate is a major metabolite of glucose in adipocytes, particularly in the large fat cells. Adipose tissue may therefore be a major site of lactate production, particularly in states of altered glucose metabolism (i.e., hyperglycemia) and obesity.

Adipose Tissue↗

PubMed1983

Prolonged effects of fasting-refeeding on rat adipose tissue lipoprotein lipase activity: influence of caloric restriction during refeeding.

We studied lipoprotein activity in white adipose tissue of male rats during a 3-day fast and up to 21 days of refeeding. Changes in LPL were considered in relation to concomitant changes in fat cell size. During fasting fat cell size decreased and LPL activity declined markedly (80%). With ad libitum refeeding LPL activity returned to control values by 3 or 5 days of refeeding, increased above control values (60-100%) by 10 days of refeeding and returned to control values by 20 days of refeeding. The normalization and overshoot of LPL activity preceded and accompanied increases in fat cell size, which occurred between days 5 and 10 of refeeding; LPL activity returned to control values Only after fat cell size also returned to control values. Mild food restriction (approximately 25%) during refeeding allowed LPL activity to return to control values but reduced the magnitude and duration of the overshoot. Severe food restriction (approximately 50%) during refeeding delayed the return of LPL activity to control values until day 20 of refeeding. These data support a role for LPL in restoration of adipocyte lipid stores during refeeding. Food restriction during refeeding influences LPL and may modulate the rate of lipid accumulation by adipocytes during refeeding.

Adipose Tissue↗