Biomedical subjects

G Liverini

Publications and source records attributed to G Liverini.

At least 19 recordsLinked to original sources

PubMed2006

Heterogeneous bioenergetic behaviour of subsarcolemmal and intermyofibrillar mitochondria in fed and fasted rats.

This study was designed to examine energetic behaviour of skeletal muscle subsarcolemmal and intermyofibrillar mitochondrial populations. The data show that subsarcolemmal mitochondria exhibited a lower degree of coupling and efficiency than intermyofibrillar ones, and can therefore be considered less efficient at producing ATP. In addition, subsarcolemmal mitochondria showed an increased sensitivity to palmitate-induced uncoupling, in line with high adenine nucleotide translocator content and decreased oxidative damage. We then determined the effect of 24 h fasting on energetic characteristics of skeletal muscle mitochondrial populations. We found that fasting enhanced proton leak and decreased the degree of coupling and efficiency, both in the absence and in the presence of palmitate only in subsarcolemmal mitochondria. Moreover, this mitochondrial population showed lower oxidative damage, probably due to a counter-regulatory mechanism mediated by uncoupling protein 3. Subsarcolemmal and intermyofibrillar mitochondria appear to exhibit different energetic characteristics and can be differently affected by physiological stimuli.

Aconitate Hydratase↗

PubMed2004

Modulation of hepatic mitochondrial energy efficiency with age.

This study was designed to examine the effect of youth-adulthood transition on hepatic mitochondrial energy efficiency. The changes in basal and palmitate-induced proton leak, which contribute to mitochondrial efficiency, were evaluated in mitochondria isolated from the liver of young and adult rats. Alterations in mitochondrial cytochrome oxidase and aconitase specific activities, and in adenine nucleotide translocator content were also assessed. There was no difference in basal proton leak or thermodynamic coupling and efficiency of oxidative phosphorylation in liver mitochondria between the two rat groups. On the other hand, palmitate-induced proton leak increased significantly in adult rats. The function of this uncoupling could be avoidance of elevated formation of reactive oxygen species, which are known to accelerate ageing.

Aconitate Hydratase↗

PubMed2003

Skeletal muscle mitochondrial oxidative capacity and uncoupling protein 3 are differently influenced by semistarvation and refeeding.

We investigated, in skeletal muscle mitochondria isolated from semistarved and refed rats, the relation between the protein expression of uncoupling protein 3 (UCP3) and mitochondrial oxidative capacity, assessed as state 4 and state 3 respiration rates in presence of substrates that are either non-lipids (glutamate, succinate) or lipids (palmitoyl CoA, palmitoylcarnitine). During semistarvation, when whole-body thermogenesis is diminished, state 3 respiration was lower than in fed controls by about 30% independently of substrate types, while state 4 respiration was lower by 20% only during succinate oxidation, but UCP3 was unaltered. After 5 days of refeeding, when thermogenesis is still diminished, neither state 4, state 3 nor UCP3 were lower than in controls. Refeeding on a high-fat diet, which exacerbates the suppression of thermogenesis, resulted in a two-fold elevation in UCP3 but no change in state 4 or state 3 respiration. These results during semistarvation and refeeding, in line with those previously reported for fasting, are not in support of the hypothesis that UCP3 is a mediator of adaptive thermogenesis pertaining to weight regulation, and underscore the need for caution in interpreting parallel changes in UCP3 and mitochondrial oxidative capacity as the reflection of mitochondrial uncoupling by UCP3.

Animal Feed↗

PubMed2002

Skeletal muscle oxidative capacity in rats fed high-fat diet.

OBJECTIVE: To investigate whether young rats respond to high-fat feeding through changes in energy efficiency and fuel partitioning at the level of skeletal muscle, to avoid obesity development. In addition, to establish whether the two mitochondrial subpopulations, which exist in skeletal muscle, ie subsarcolemmal and intermyofibrillar, are differently affected by high-fat feeding. DESIGN: Weaning rats were fed a low-fat or a high-fat diet for 15 days. MEASUREMENTS: Energy balance and lipid partitioning in the whole animal. State 3 and state 4 oxygen consumption rates in whole skeletal muscle homogenate. State 3 and state 4 oxygen consumption rates, membrane potential and uncoupling effect of palmitate in subsarcolemmal and intermyofibrillar mitochondria from skeletal muscle. RESULTS: Rats fed a high-fat diet showed an increased whole body lipid utilization. Skeletal muscle NAD-linked and lipid oxidative capacity significantly increased at the whole-tissue level, due to an increase in lipid oxidative capacity in subsarcolemmal and intermyofibrillar mitochondria and in NAD-linked activity only in intermyofibrillar ones. In addition, rats fed a high-fat diet showed an increase in the uncoupling effect of palmitate in both the mitochondrial populations. CONCLUSIONS: In young rats fed a high-fat diet, skeletal muscle contributes to enhanced whole body lipid oxidation through an increased mitochondrial capacity to use lipids as metabolic fuels, associated with a decrease in energy coupling.

Animal Feed↗

PubMed2001

Differences in proton leak kinetics, but not in UCP3 protein content, in subsarcolemmal and intermyofibrillar skeletal muscle mitochondria from fed and fasted rats.

We have investigated the effect of 24-h fasting on basal proton leak and uncoupling protein (UCP) 3 expression at the protein level in subsarcolemmal and intermyofibrillar skeletal muscle mitochondria. In fed rats, the two mitochondrial populations displayed different proton leak, but the same protein content of UCP3. In addition, 24-h fasting, both at 24 and 29 degrees C, induced an increase in proton leak only in subsarcolemmal mitochondria, while UCP3 content increased in both the populations. From the present data, it appears that UCP3 does not control the basal proton leak of skeletal muscle mitochondria.

Animals↗

PubMed2001

Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats.

The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production.

Acetyl-CoA C-Acyltransferase↗

PubMed2001

Fat balance and serum leptin concentrations in normal, hypothyroid, and hyperthyroid rats.

OBJECTIVE: To study the influence of thyroid hormones on the relationship between serum leptin and fat mass, as well as on energy and macronutrient balance. DESIGN: Rats with different thyroid states were obtained by 7 and 15 days of treatment with the antithyroid drug propylthiouracil or with triiodothyronine (T3). MEASUREMENTS: Energy balance, macronutrient balance and serum leptin concentrations. RESULTS: In hypothyroid rats we found a decrease in metabolizable energy (ME) intake and energy expenditure together with an increase in lipid gain/lipid intake ratio and a decrease in protein gain/protein intake ratio. Consequently, body lipid percentage significantly increased compared to euthyroid rats. Hyperthyroid rats first increased energy expenditure and later ME intake, so that increased metabolism was balanced by increased intake, and energy gain was similar to that found in euthyroid rats. CONCLUSION: These results indicate that T3 plays a major role in the maintenance of energy and lipid balance. Our results also indicate that an inverse relationship exists between T3 and leptin serum concentrations, and that this relationship is not only the result of changes in body fat stores induced by changed T3 concentrations.

Adipose Tissue↗

PubMed2001

Mitochondrial respiration and triiodothyronine concentration in liver from postpubertal and adult rats.

The purpose of this study was to investigate the decline in rat liver mitochondria respiration found in adult rats compared to younger ones, and to find a link between this respiratory impairment and a tissue hypothyroidism state. To this end, hepatic concentration and serum levels of triiodothyronine were measured in postpubertal rats (60 days old) and adult rats (180 days old). In addition, in these rats we measured oxidative phosphorylation in homogenate together with coupled and uncoupled respiration in isolated mitochondria using succinate or durohydroquinone as substrate. We found that mitochondria from adult rats consumed less oxygen compared to younger rats due to lower electron transport chain and phosphorylating system activity. In addition, we found that in state 4 condition, mitochondria from adult rats consumed less oxygen than mitochondria from young rats. Finally, we found a decrease in liver triiodothyronine concentration in adult rats. In conclusion, the results of this study show that hepatic mitochondria in adult rats have a decreased ATP synthesis capacity and proton permeability, both consistent with the tissue hypothyroidism found in the liver of adult rats.

Adenosine Triphosphate↗

PubMed2001

Effect of cold exposure on energy balance and liver respiratory capacity in post-weaning rats fed a high-fat diet.

Variations in energy balance, body composition, and nutrient partitioning induced by high-fat feeding, cold exposure or by concomitant high-fat feeding and cold exposure were studied in young Wistar rats. Changes in hepatic metabolism as well as in serum free triiodothyronine and leptin levels were also evaluated. Rats were exposed to either 24 or 4 degrees C and fed either a low- or high-fat diet (10 % or 50 % energy respectively) for 2 weeks. Relative to low-fat feeding at 24 degrees C, both energy intake and expenditure were increased by high-fat feeding or by cold exposure, and these changes were accompanied by increased serum triiodothyronine levels. In response to concomitant high-fat feeding and cold exposure, serum triiodothyronine tended to be further elevated, but no further increases in energy intake or energy expenditure were observed. Independently of diet, the increased energy expenditure in cold-exposed rats was not completely balanced by adaptive hyperphagia, with consequential reductions in protein and fat gain, accompanied by marked decreases in serum leptin. Furthermore, unlike high-fat feeding at 24 degrees C, cold exposure enhanced hepatic mitochondrial oxidative capacity both in the low-fat- and high-fat-fed groups. It is concluded that in this strain of young Wistar rats, despite similarly marked stimulation of energy expenditure by high-fat feeding at 24 degrees C, by cold exposure and by concomitant high-fat feeding and cold exposure, an increased hepatic oxidative capacity occurred only in the presence of the cold stimulus.

Animals↗

PubMed2000

Effect of long-term high-fat feeding on energy balance and liver oxidative activity in rats.

The purpose of this work was to study the effect of early long-term high-fat feeding on energy balance and liver oxidative activity. To this end, rats aged about 30 d were fed a high-fat or a low-fat diet for 15, 30 or 60 d. Full energy balance and energy partitioning measurements were carried out. In addition, we measured hepatic mitochondrial and peroxisomal oxidative capacities. Serum levels of free triiodothyronine (T3) and leptin were also determined. Rats fed a high-fat diet showed an increase in metabolizable energy intake as well as in energy expenditure, while lipid gain over the whole period was lower than that expected due to a decrease in metabolic efficiency. An increase in serum free T3 levels was also found in rats fed a high-fat diet after 15 and 30 d. Statistically significant correlations between serum leptin levels and body fat mass were found after 15, 30 and 60 d of high-fat feeding. Finally, no variation in hepatic mitochondrial and peroxisomal fatty acid oxidation capacity was found in rats fed a high-fat diet for 15, 30 or 60 d. In conclusion, the results of the present study show that young Wistar rats fed a high-fat diet for up to 60 d are able to counteract, at least in part, obesity development.

Animals↗

PubMed1999

Stimulation of oxygen consumption following addition of lipid substrates in liver and skeletal muscle from rats fed a high-fat diet.

We studied hepatic and skeletal muscle metabolic activity in rats fed a high-fat diet. Rats were fed a low-fat or high-fat diet for 15 days. At the end of the experimental period, full energy-balance determinations together with serum free triiodothyronine (FT3), leptin, and free fatty acid (FFA) measurements were performed. In addition, we assessed fatty acid-stimulated oxygen consumption in perfused liver and in skeletal muscle homogenate. Rats fed a high-fat diet showed a significant increase in energy intake but no variation in body energy gain, due to a significant increase in energy expenditure. Serum FT3 and FFA levels significantly increased in rats fed a high-fat diet versus rats fed a low-fat diet, while no variation was found in serum leptin levels. Perfused livers and skeletal muscle homogenates from rats fed a high-fat diet exhibited a significant increase in fatty acid-stimulated oxygen consumption. Our results suggest that the enhanced fatty acid oxidation rates in liver and skeletal muscle contribute to the maintenance of fat balance in response to increased fat intake, preventing excess fat deposition.

Animals↗

PubMed1999

Fat balance and hepatic mitochondrial function in response to fat feeding in mature rats.

OBJECTIVE: To study the effects of fat feeding on fat balance and hepatic mitochondrial function in postpubertal male rats. DESIGN: Rats were fed low fat, medium fat or high fat diet for 15 days. MEASUREMENTS: Energy balance, body composition, resting metabolic rate (RMR), mitochondrial state 3 and state 4 oxygen consumption rates, succinic dehydrogenase (EC 1.3.99.1) and mitochondrial alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) activities. RESULTS: Rats fed medium fat or high fat diet, in comparison with rats fed low fat diet, showed a significantly greater metabolisable energy intake and energy expenditure. In addition, body energy and lipid gains were significantly higher in rats fed medium fat or high fat diet than in rats fed low fat diet. Mitochondrial respiration and enzymatic activities were not affected by fat feeding. CONCLUSION: These results indicate that in postpubertal rats fed high fat diets, the increase in energy expenditure counteracts only in part the excess fat deposition. This is probably due to the impairment in regulatory responses, and enhances thermogenesis.

Adipose Tissue↗

PubMed1999

Energy intake and utilization vary during development in rats.

Energy intake, utilization, and partitioning were determined in male Wistar rats from 25 to 180 d of age. Serum free triiodothyronine, leptin, and free fatty acid concentrations were also measured. Energy balance measurements allowed us to identify a period from 25 to 90 d, characterized by a rapid body growth rate and another from 90 to 180 d, during which body growth rate slowed. From 25 to 180 d, we found decreases in daily energy intake and expenditure, which were faster before 90 d. The first period was characterized by storage of lipid and protein. In the second period, protein deposition approached zero and the excess of ingested energy was entirely stored as fat, so that age-associated obesity began to develop. The inability of rats to maintain a stable body weight after the cessation of growth of lean body mass is not due to decreased resting metabolism but rather to a partial leptin resistance.

Adipose Tissue↗

PubMed1998

Changes in the hepatic mitochondrial respiratory system in the transition from weaning to adulthood in rats.

In the present study we investigated the changes in the hepatic mitochondrial respiratory system in the transition from weaning to adulthood in the rat. We conceptually divided the system into blocks of reactions that produced or consumed mitochondrial membrane potential and then measured the kinetic responses of these blocks of reactions to changes in this potential in isolated liver mitochondria from 25- and 60-day-old rats using succinate as substrate. Moreover, we considered the mitochondrial membrane potential producers to be divided into blocks of reactions that reduced or oxidized ubiquinone-2 (Q-2) and then measured the kinetic responses of these two blocks to changes in Q-2 redox state as well as the flux control coefficients and the cytochrome content. We found that adult rats exhibited significantly higher state 3 respiratory rates with increased kinetic response of the substrate oxidation pathway to the mitochondrial membrane potential, slightly decreased activity of the phosphorylating system, increased kinetic responses of both Q-2 reducers and oxidizers to Q-2 redox state, and increased cytochrome content. Our results indicate that important changes in the hepatic mitochondrial respiratory system occur in the transition from weaning to adulthood in rats.

Age Factors↗

PubMed1998

Rat liver mitochondrial respiratory capacities in the transition from weaning to adulthood.

In the present study we investigated the changes in hepatic mitochondrial function in the transition from weaning to adulthood in the rat. We measured mitochondrial respiration using FAD- and NAD-linked substrates in 25 and 60 day old rats. The results show that adult rats exhibited significantly higher respiratory rates with all the substrates used except pyruvate. Our results indicate that the transition from weaning to adulthood induces important changes in hepatic mitochondrial function.

Aging↗

PubMed1998

Oxidative activity in mitochondria isolated from rat liver at different stages of development.

The purpose of this study was to evaluate the oxidative capacities in hepatic mitochondria isolated from prepubertal, young adult and adult rats (40, 90 and 180 days of age, respectively). In these rats, mitochondrial respiratory rates using FAD- and NAD-linked substrates as well as mitochondrial protein mass were measured. The results show that only the oxidative capacity of FAD-linked pathways significantly declined in mitochondria from 180-day-old rats compared with those from younger animals. When we consider FAD-linked respiration expressed per g liver, no significant difference was found among rats of different ages because of an increased mitochondrial protein mass found in 180-day-old rats. However, when FAD-linked and lipid-dependent respiratory rates were expressed per 100 g body weight, significant decreases occurred in 180-day-old rats. Therefore, the decrease in liver weight expressed per 100 g body weight rather than an impaired hepatic cellular activity may be the cause of body energy deficit in 180-day-old rats.

Animals↗

PubMed1998

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development.

Changes in mitochondrial function were studied in perfused liver from rats aged 24-365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage.

Age Factors↗

PubMed1998

Steady state changes in mitochondrial electrical potential and proton gradient in perfused liver from rats fed a high fat diet.

In this work the protonmotive force (delta p), as well as the subcellular distribution of malate, ATP, and ADP were determined in perfused liver from rats fed a low fat or high fat diet, using density gradient fractionation in non aqueous solvents. Rats fed a high fat diet, despite an enhanced hepatic oxygen consumption, exhibit similar delta p to that found in rats fed a low fat diet, but when we consider the two components of delta p, we find a significant decrease in mitochondrial/cytosolic pH difference (delta pH(m)) and a significant increase in mitochondrial membrane potential (delta psi(m)) in rats fed a high fat diet compared to rats fed a low fat diet, which tend to compensate each other. In rats fed a high fat diet the concentration ratio of malate and ATP/ADP does not reflect the changes in delta pH(m) and delta psi(m), which represent the respective driving force for their transport. The findings are in line with an increase in substrate supply to the respiratory chain which is, however, accompanied by a higher energy turnover in livers from HFD rats. By this way the liver could contribute to the lack of weight gain from the high caloric intake in HFD rats.

Adenosine Diphosphate↗