17 research outputs found
Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-α
The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsuli-naemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonely) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone
Diet-Independent Remodeling of Cellular Membranes Precedes Seasonally Changing Body Temperature in a Hibernator
Polyunsaturated fatty acids (PUFA) have a multitude of health effects. Their incorporation into membrane phospholipids (PL) is generally believed to depend directly on dietary influx. PL influence transmembrane protein activity and thus can compensate temperature effects; e.g. PL n-6 PUFA are thought to stabilize heart function at low body temperature (Tb), whereas long chain (>C18) n-3 PUFA may boost oxidative capacity. We found substantial remodeling of membranes in free-living alpine marmots which was largely independent of direct dietary supply. Organ PL n-6 PUFA and n-6 to n-3 ratios were highest at onset and end of hibernation after rapid increases during a brief transitional period prior to hibernation. In contrast, longer chain PL n-3 PUFA content was low at end of summer but maximal at end of hibernation. After termination of hibernation in spring, these changes in PL composition were rapidly reversed. Our results demonstrate selective trafficking of PUFA within the body, probably governed by a circannual endogenous rhythm, as hibernating marmots were in winter burrows isolated for seven months from food and external cues signaling the approaching spring. High concentrations of PL n-6 PUFA throughout hibernation are in line with their hypothesized function of boosting SERCA 2a activity at low Tb. Furthermore, we found increasing rate of rewarming from torpor during winter indicating increasing oxidative capacity that could be explained by the accumulation of long-chain PL n-3 PUFA. It may serve to minimize the time necessary for rewarming despite the increasing temperature range to be covered, because rewarming is a period of highest metabolic rate and hence production of reactive oxygen species. Considering the importance of PUFA for health our results may have important biomedical implications, as seasonal changes of Tb and associated remodeling of membranes are not restricted to hibernators but presumably common among endothermic organisms
The role of nitric oxide in remodeling of capillary network in rat interscapular brown adipose tissue after long-term cold acclimation
Cold exposure has been shown to increase
blood flow in interscapular brown adipose tissue (IBAT).
The aim of the present study was to evaluate the role of
the L-arginine-nitric oxide (•NO) pathway on IBAT
capillary network remodeling and its possible correlation
with superoxide anion radical (O2
•–). In the rats that
received L-arginine (2.25%) or NG-nitro-L-arginine
methyl ester (L-NAME, 0.01%) as a drinking liquid and
maintained at room (22±1°C) or low (4±1°C)
temperature for 45 days, IBAT capillaries were analyzed
by stereology and observed by light and electron
microscopy. Additionally, endothelial •NO synthase
(eNOS) expression, nitrotyrosine immunoreactivity and
both copper zinc superoxide dismutase (CuZnSOD)
enzyme activity and immunohistochemical localization
were examined. Stereological analyses of IBAT show
that the capillary volume density, as well as capillary-tobrown
adipocytes ratio, are increased in cold. L-arginine
treatment increases, while L-NAME decreases both
parameters, compared to respective controls. Those
changes were accompanied by capillary dilatation
observed by light and electron microscopy. The activity
of CuZnSOD is lower in control cold-acclimated rats, as
well as in both L-arginine-treated groups, when
compared to control animals acclimated to room
temperature. L-NAME treatment attenuates the effects
both of cold and L-arginine on CuZnSOD and increases
immunopositivity for CuZnSOD in room temperatureacclimated
rats. Our results show that •NO induces
remodeling of the IBAT capillary network by
angiogenesis, and presumably that interaction with O2
•–
has a role in that modulation. The increased eNOS
expression accompanied by an increased nitrotyrosine
immunoreaction observed in both L-arginine-treated groups compared to corresponding controls strengthens
this hypothesis
Targeting the nitric oxide/superoxide ratio in adipose tissue: relevance in obesity and diabetes management
Insulin sensitivity and metabolic homeostasis depend on the capacity of adipose tissue to take up and utilise excess glucose and fatty acids. The key aspects that determine the fuel-buffering capacity of adipose tissue depend on the physiological levels of the small redox molecule, nitric oxide (NO). In addition to impairment of NO synthesis, excessive formation of superoxide (capital O, Cyrillic2 *- ) in adipose tissue may be an important interfering factor diverting the signalling of NO and other reactive oxygen and nitrogen species (ROS/RNS) in obesity, resulting in metabolic dysfunction of adipose tissue over time. Besides its role in relief from superoxide burst, enhanced NO signalling may be responsible for the therapeutic benefits of different superoxide dismutase mimics in obesity and experimental diabetes models. This review summarises the role of NO in adipose tissue and highlights the impact of NO/capital O, Cyrillic2 *- ratio "teetering" as a promising pharmacological target in metabolic syndrome. This article is protected by copyright. All rights reserved
The impact of cold acclimation and hibernation on antioxidant defenses in the ground squirrel (Spermophilus citellus): An update
Any alteration in oxidative metabolism is coupled with a corresponding response by an antioxidant defense (AD) in appropriate subcellular compartments. Seasonal hibernators pass through circannual metabolic adaptations that allow them to either maintain euthermy (cold acclimation) or enter winter torpor with body temperature falling to low values. The present study aimed to investigate the corresponding pattern of AD enzyme protein expressions associated with these strategies in the main tissues involved in whole animal energy homeostasis: brown and white adipose tissues (BAT and WAT, respectively), liver, and skeletal muscle. European ground squirrels (Spermophilus citellus) were exposed to low temperature (4 ± 1 C) and then divided into two groups: (1) animals fell into torpor (hibernating group) and (2) animals stayed active and euthermic for 1, 3, 7, 12, or 21 days (cold-exposed group). We examined the effects of cold acclimation and hibernation on the tissue-dependent protein expression of four enzymes which catalyze the two-step detoxification of superoxide to water: superoxide dismutase 1 and 2 (SOD 1 and 2), catalase (CAT), and glutathione peroxidase (GSH-Px). The results showed that hibernation induced an increase of AD enzyme protein expressions in BAT and skeletal muscle. However, AD enzyme contents in liver were largely unaffected during torpor. Under these conditions, different WAT depots responded by elevating the amounts of specific enzymes, as follows: SOD 1 in retroperitoneal WAT, GSH-Px in gonadal WAT, and CAT in subcutaneous WAT. Similar perturbations of AD enzymes contents were seen in all tissues during cold acclimation, often in a time-dependent manner. It can be concluded that BAT and muscle AD c