Rat Adipose Tissue Metabolism Research Articles

Time-of-day dependent effect of proanthocyanidins on adipose tissue metabolism in rats with diet-induced obesity.

Grape-seed proanthocyanidin extract (GSPE) improve white adipose tissue (WAT) expansion during diet-induced obesity. However, because adipose metabolism is synchronized by circadian rhythms, it is plausible to speculate that the bioactivity of dietary proanthocyanidins could be influenced by the time-of-day in which they are consumed. Therefore, the aim of the present study was to determine the interaction between zeitgeber time (ZT) and GSPE consumption on the functionality of WAT in rats with diet-induced obesity. Male Wistar rats were fed a cafeteria diet for 9 weeks. After 5 weeks, the animals were supplemented with 25 mg GSPE/kg for 4 weeks at the beginning of the light/rest phase (ZT0) or of the dark/active phase (ZT12). Body fat content was determined by nuclear magnetic resonance and histological analyses were performed in the epididymal (EWAT) and inguinal (IWAT) fat depots to determine adipocyte size and number. In addition, the expression of genes related to adipose metabolism and circadian clock function were analyzed by qPCR. GSPE consumption at ZT0 was associated with a potential antidiabetic effect without affecting adiposity and energy intake and downregulating the gene expression of inflammatory markers in EWAT. In contrast, GSPE consumption at ZT12 improved adipose tissue expansion decreasing adipocyte size in IWAT. In accordance with this adipogenic activity, the expression of genes involved in fatty acid metabolism were downregulated at ZT12 in IWAT. In turn, GSPE consumption at ZT12, but not at ZT0, repressed the expression of the clock gene Cry1 in IWAT. The interaction between ZT and GSPE consumption influenced the metabolic response of WAT in a tissue-specific manner. Understanding the impact of circadian clock on adipose metabolism and how this is regulated by polyphenols will provide new insights for the management of obesity.

Exercise training enhances white adipose tissue metabolism in rats selectively bred for low- or high-endurance running capacity

Impaired visceral white adipose tissue (WAT) metabolism has been implicated in the pathogenesis of several lifestyle-related disease states, with diminished expression of several WAT mitochondrial genes reported in both insulin-resistant humans and rodents. We have used rat models selectively bred for low- (LCR) or high-intrinsic running capacity (HCR) that present simultaneously with divergent metabolic phenotypes to test the hypothesis that oxidative enzyme expression is reduced in epididymal WAT from LCR animals. Based on this assumption, we further hypothesized that short-term exercise training (6 wk of treadmill running) would ameliorate this deficit. Approximately 22-wk-old rats (generation 22) were studied. In untrained rats, the abundance of mitochondrial respiratory complexes I-V, citrate synthase (CS), and PGC-1 was similar for both phenotypes, although CS activity was greater than 50% in HCR (P = 0.09). Exercise training increased CS activity in both phenotypes but did not alter mitochondrial protein content. Training increased the expression and phosphorylation of proteins with roles in β-adrenergic signaling, including β3-adrenergic receptor (16% increase in LCR; P < 0.05), NOR1 (24% decrease in LCR, 21% decrease in HCR; P < 0.05), phospho-ATGL (25% increase in HCR; P < 0.05), perilipin (25% increase in HCR; P < 0.05), CGI-58 (15% increase in LCR; P < 0.05), and GLUT4 (16% increase in HCR; P < 0.0001). A training effect was also observed for phospho-p38 MAPK (12% decrease in LCR, 20% decrease in HCR; P < 0.05) and phospho-JNK (29% increase in LCR, 20% increase in HCR; P < 0.05). We conclude that in the LCR-HCR model system, mitochondrial protein expression in WAT is not affected by intrinsic running capacity or exercise training. However, training does induce alterations in the activity and expression of several proteins that are essential to the intracellular regulation of WAT metabolism.

Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained rats

The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity.

Pinealectomy impairs adipose tissue adaptability to exercise in rats

This study investigated the effects of pinealectomy and exercise training on rat adipose tissue metabolism. Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were subdivided into four subgroups, including PINX untrained, PINX trained, CONTROL untrained and CONTROL trained. At the end of the training period (8 wk), the rats were killed and peri-epididymal adipocytes were isolated for in vitro insulin-stimulated glucose uptake, conversion of D-[U-14C]-glucose, l-[U-14C]-lactate, [2-14C]-acetate and [1-14C]-palmitate into 14CO2, and insulin binding. Pinealectomy resulted in a significantly decreased insulin-stimulated glucose uptake in adipocytes without affecting insulin-binding capacity. However, in intact control animals only, training promoted a higher baseline glucose uptake in adipocytes. Training influenced the adipocyte ability to oxidize the different substrates: the rates of glucose and palmitate oxidation increased while the rates of lactate and acetate diminished. Nevertheless, these effects of exercise training were not seen in pinealectomized rats. Additionally, an increase in palmitate oxidation was observed in sedentary pinealectomized animals. In conclusion, these data show that the pineal gland alters the patterns of substrate utilization by the adipocyte, in such a way that its absence disrupts the ability to adapt to the metabolic demands evoked by exercise training in rats.

Pinealectomy alters adipose tissue adaptability to fasting in rats

This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism, as well as on profiles of the hormones directly involved in its regulation (insulin, leptin, and corticosterone). Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were killed 6 weeks after surgery, in either fed or fasted (12 and 36 hours) states. Blood samples (for glucose and hormone determinations) and peri-epididymal adipocytes (for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids) were collected. Pineal ablation decreased insulin-stimulated glucose uptake in adipocytes of both fed and fasted animals without affecting insulin-binding capacity. Pinealectomy attenuated the reduction in the ability to oxidize glucose in both basal and insulin-stimulated states during fasting. This alteration in the ability of adipocytes to oxidize glucose appeared together with a decrease in insulin-induced glucose incorporation into lipids in PINX animals. Additionally, pinealectomized rats showed higher corticosterone levels in both fed and fasted states, and a lower leptinemia with 36 hours of fasting, in comparison to CONTROLs. In conclusion, our data reinforce the hypothesis that the pineal gland has a role in the modulation of adipocyte metabolism, and its absence alters metabolic adaptation to fasting in rats.

Anti-glucocorticoid effects of progesterone in vivo on rat adipose tissue metabolism

Steroid hormones seem to be important for adipose tissue metabolism and accumulation. As progesterone has been suggested to modulate the glucocorticoid effects, the interactions between glucocortioid and progesterone on adipose tissue metabolism were investigated. Forty-eight male Wistar rats were adrenectomized and divided into four groups; controls (treated with vehicle only), dexamethasone treated (10 μg per rat), progesterone treated (5 mg per rat) and the last group received both dexamethasone and progesterone. The dexamethasone-treated group had a significant loss of body weight and smaller intra-abdominal fat depots compared to the control group in addition, dexamethasone increased LPL-activity and increased catecholamine stimulated lipolysis. When progesterone was given concomitantly the dexamethasone effects on adipose tissue mass, LPL-activity and lipolysis were blocked. When given alone progesterone had no influence on body weight, amount of adipose tissue, lipolysis or LPL-activity. These data indicate that progesterone acts as an anti-glucocorticoid in adipose tissue in vivo, thus attenuating the glucocorticoid effect on adipose tissue metabolism.

Chronic effects of dehydroepiandrosterone on rat adipose tissue metabolism

The goal of the present study was to examine cellular mechanisms that regulate adipose cell metabolism in ovariectomized (OVX) and intact rats that were subjected to long-term (27 weeks) treatment with dehydroepiandrosterone (DHEA). Forty-eight 16-month-old female rats were divided into 4 groups of 9 to 11 animals (intact, intact-DHEA, OVX, OVX-DHEA). Adipose tissue lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), and cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (cAMP-PDE) activities were determined, and α2-, β1/β2-, and β3-adrenoceptors (ARs) were quantified. DHEA did not affect body weight, fat, or muscle mass in intact rats. The similar retroperitoneal fat pad weight of intact-DHEA rats compared to intact animals was in agreement with the lack of difference in the enzyme activities and AR densities. The increased body weight of OVX rat was paralleled by a greater retroperitoneal adipose tissue mass (P <.01), which was in turn associated with a marked rise in LPL activity (P <.005) and a slight decrease in HSL activity (P <.05) compared to intact animals. OVX-DHEA rats, compared to untreated OVX animals, had a smaller retroperitoneal fat depot, which correlated with a decrease in LPL activity (P <.005) and moderate increase in both HSL activity and β3-AR density (P <.05). DHEA-treatment lowered fasting insulin and triglyceride levels in both intact and OVX rats (P <.05). Plasma testosterone, androsterone, androstenedione, and androstenediol levels were also significantly increased in both intact-DHEA and OVX-DHEA rats compared to untreated animals (P <.0001). These findings suggest that the antiobesity action of DHEA may be related in part to changes in lipase activities and in β3-AR density, and that it is dependent on the ovarian status of the animal. Copyright 2003, Elsevier Science (USA). All rights reserved.

Effect of a long-term percutaneous adrenal steroid treatment on rat adipose tissue metabolism.

To examine some cellular mechanisms which regulate adipose cell metabolism in ovariectomized (OVX) and intact rats subjected or not to dehydroepiandrosterone (DHEA). Rats were assigned to one of four treatment groups for 27 weeks. The main effects tested were castration (-or+) and DHEA treatment (-or+) which consisted of a single daily percutaneous application of DHEA cream (30 mg/ml in 50% ethanol-50% propyleneglycol). Forty female Sprague- Dawley rats (sixteen-month old). Body weight and fat mass (by dual-energy X-ray absorptiometry), retroperitoneal (RP) fat pad weight; plasma insulin and triglyceride levels, and HDL-cholesterol (C) concentrations; lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities. No difference in body composition and RP fat pad weight was observed between the intact and intact-DHEA groups. LPL and HSL activities were also similar in both groups. The increased weight of OVX rats was paralleled by a higher adiposity and greater RP adipose tissue mass, which was associated with both a marked rise in LPL activity and a slight diminution in HSL activity in this depot, compared to intact animals. OVX-DHEA rats displayed a reduced adiposity and a lighter RP fat depot, which was associated with a decrease in LPL and an increase in HSL activities, compared to untreated OVX animals. Fasting plasma insulin and TG levels were also decreased whereas plasma HDL-C concentrations were increased in intact-DHEA and OVX-DHEA rats. These results show that the antiobesity effects of DHEA are dependent upon the ovarian status of the animal. These effects may involve changes in the lipid storage and the mobilization capacity of adipose tissue.

In vitro biological effects of a low molecular weight somatomedin inhibitory fraction extracted from normal serum

Gel chromatography of normal human serum exhibits a low molecular weight fraction, which significantly inhibits the action of somatomedin on porcine rib cartilage segments. This somatomedin inhibitory fraction (SmIF) has a molecular weight of about 1250 daltons, an iso-electric point between 5 to 5.5 and shows several characteristics of a peptide nature (Ped. Res. 18:101,1984). This SmIF strongly reduces both 35S-sulphate and 3H-Thymidine incorporation into costal cartilage of young pigs and rabbits and 35S-sulphate uptake by embryonic chick cartilage. This effect is dose-dependent, both in basal and in serum stimulated conditions, and is reversible. To a similar extent, SmIF decreases the conversion of 14C-glucose into 14CO2 in epididymal fat pads of young rats, with or without addition of normal serum, insulin or triiodothyronine. In conclusion, this low molecular weight SmIF does not only inhibit specifically the in vitro action of somatomedin on cartilage of several animal species, but also counteracts the insulin-like activity of normal serum and the effect of insulin and triiodothyronine on glucose metabolism of rat adipose tissue.

Alterations of Rat Adipose Tissue Metabolism Associated with Dietary Chromium Supplementation

Net free fatty acid release from adipose tissue taken from male rats fed a stock diet unsupplemented with chromium was significantly greater than that from adipose tissue taken from chromium-supplemented rats. This enhanced net lipolysis was unaccompanied by any evidence of a compensatory increase in reesterification. Specifically, the glycerokinase-catalyzed direct phosphorylation of glycerol, which might have provided an alternate supply of alpha-glycerophosphate for reesterification in the absence of glycolytic production of alpha-glycerophosphate, was significantly reduced. These animals also showed an abnormal glucose tolerance response. In contrast, male rats fed a purified diet unsupplemented with chromium appeared to be marginally chromium-deficient as judged by a glucose tolerance test but did not show any alterations in adipose tissue metabolism attributable to the adequacy of chromium nutriture.

Influence of tetrahydropapaveroline on adipose tissue metabolism in comparison with that of noradrenaline, theophylline and papaverine

The influence of tetrahydropapaveroline (THP) (an alkaloid structurally related to the catecholaminesand that can be biosynthesized in vivo from dopamine) on rat adipose tissue metabolism was investigated in vitro at the level of cAMP accumulation and FFA release, and a comparison was made with noradrenline, theophylline and papaverine. No significant difference was found between noradrenaline and THP lipolytic activity, but the alkaloid was more effective in increasing cAMP levels. Theophylline by itself does not alter the nucleotide content in these experiments, but potentiates the action of the alkaloid and, at a still higher rate, that of the hormone. Papaverine is not effective on cyclic AMP synthesis either in basal conditions or in the presence of noradrenaline. From these results the hypothesis was put forth that THP has an inhibitory effect on an adipose tissue phosphodiesterase, but this enzyme could be different from that influenced by papaverine.

Effects of age and cell size on rat adipose tissue metabolism.

In order to analyze separately the effects of cell size and age on the metabolism of rat adipose tissue, fat cells of different sizes were obtained from the same animals. The rats were 4 or 15 wk old. The results show that age as well as cell size influences the metabolic rates. At a given cell size, the basal lipolysis, the lipolytic effects of glucagon and noradrenaline, the rate of glucose incorporation into the triglycerides, and the effect of insulin on glucose metabolism were considerably increased in the young animals. Furthermore, irrespective of fat cell size the lipolytic action of glucagon was reduced in old animals. The data thus show that experiments with large fat cells from old rats and with small cells from young animals cannot be directly compared because both variables may influence metabolic reactions.

Control of rat adipose tissue metabolism by cortisone in relation to epinephrine.

Control of rat adipose tissue metabolism by cortisone in relation to epinephrine.

The influence of diuretic agents on the insulin stimulated glucose metabolism of rat adipose tissue in vitro and in vivo

Comparative experiments were carried outin vitro on cell suspensions and cell-free enzyme extracts of epididymal fat tissue andin vivo to find out whether furosemide, acetazolamide and ethacrynic acid have an effect on the insulin-stimulated metabolism of glucose in rat adipose tissue. Typical inhibition curves were used to demonstrate the influence of the concentration of the diuretic agents in a protein-free medium on the oxidation of glucose-1-14C and14CO2-fixation in cell suspensions. Irrespective of the addition of insulin, the inhibition constants for glucose oxidation and CO2-fixation were found to be 2 ⋅ 10−4M for acetazolamide and 5 ⋅ 10−5M for ethacrynic acid. Using furosemide, the maximal inhibition obtained was 30 % at a concentration of 6 ⋅ 10−4M. In each case the addition of albumin to the medium prevented the inhibition completely, presumably due to protein-binding. During incubation with cell-free enzyme extracts none of the diuretic agents affected glucose oxidation or CO2-fixation. In the intact animal the three diuretic agents, administered in doses of 1 ⋅ 100 mg/kg and 8 ⋅ 100 mg/kg, had no effect on the incorporation of14C-glucose into the lipids of fat tissue. After intraperitoneal injection of insulin the incorporation of14C into lipids was increased. The simultaneous administration of 1 ⋅ 100 mg/kg of acetazolamide or ethacrynic acid caused a slight reduction in the incorporation to 80 and 70 % respectively. No such effect was observed with furosemide. The results show that the reduced glucose utilization determined in isolated fat cells is probably of no importancein vivo.

The inhibitory effect of chloroquine on rat adipose tissue metabolism in vitro

Chloroquine hydrochloride, at 6.3 × 10 −5 M concentration, significantly suppressed in vitro the lipolytic actions of epinephrine, TSH, and bovine growth hormone, but not that of ACTH, as measured in the rat epididymal fat pad. A transient inhibition was also demonstrated at drug concentrations as low as 6.3 × 10 −7 M. In addition, the drug also inhibited the glucose uptake of insulin and glucagon stimulated fat pads in vitro. When oral chloroquine was fed to rats for 70 days, no inhibition of epididymal adipose tissue metabolism could be demonstrated.

The effect of growth hormone and prolactin preparations on the intermediary metabolism of rat adipose tissue

1.1. The effects of a bovine growth hormone preparation and three ovine prolactin preparations (PLR, PLC and PLF) on adipose tissue metabolism were compared with those of insulin and adrenalin. PLR and PLC were prepared using a DEAE-cellulose column, whereas PLF was prepared using Sephadex G-75. PLF contains two minor components which are largely absent from PLC. Adrenalin, bovine growth hormone, PLC and PLR increased (a) CO2 production from [6-14C]glucose; (b) glyceride-glycerol production from [I-14C]glucose to a greater extent than from [6-14C]glucose; (c) inhibited lipogenesis and (d) stimulated lipolysis. Dilution of PLC resulted in a diminution of lipolysis with a corresponding decrease in effect upon glucose metabolism. It was concluded that the effect of these pituitary hormones on glucose metabolism by rat adipose tissue is dependent upon their stimulation of lipolysis. Conversely, insulin and PLF stimulated (a) CO2 production from [I-14C]glucose; (b) lipogenesis; and (c) more glyceride-glycerol production from [6-14C]glucose than from [I-14C]glucose. PLC and bovine growth hormone reversed the stimulation of glycogen synthesis by insulin.2.2. PLC, PLF and insulin stimulated protein synthesis from [I-14C]leucine by adipose tissue taken from either normal or hypophysectomized rats. However, bovine growth hormone stimulated leucine incorporation only in tissues taken from hypophysectomized animals.3.3. It is concluded that the mode of action of prolactin on carbohydrate and lipid metabolism is dependent upon the mode of its purification, whereas its action upon protein synthesis is common to all preparations.

Extrathyroidal actions of pituitary thyrotropin: effects on the carbohydrate, lipid and respiratory metabolism of rat adipose tissue.

Extrathyroidal actions of pituitary thyrotropin: effects on the carbohydrate, lipid and respiratory metabolism of rat adipose tissue.

Effects of Epinephrine, Insulin, and Corticotrophin on the Metabolism of Rat Adipose Tissue

Effects of Epinephrine, Insulin, and Corticotrophin on the Metabolism of Rat Adipose Tissue