Lipofuscin accumulation in brown adipocytes of hyperinsulinaemic rats

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Lipofuscin accumulation in brown adipocytes of hyperinsulinaemic rats

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Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot

In this study, the effects of l-arginine-nitric-oxide ((NO)-N-a (TM))-producing pathway on protein content of ubiquitin, as an important component of ubiquitin-proteasome system for protein removal, were investigated. We showed that l-arginine markedly decreased ubiquitin protein content in interscapular brown adipose tissue, both in thermogenic inactive (at room temperature) and thermogenic active (on cold) states; while in l-NAME-treated groups this effect was abolished. This result suggests that nitric oxide ((NO)-N-a (TM)), besides well established roles, is involved in this aspect of structure remodeling, as well.Ministry of Education and Science of the Republic of Serbia [173055

Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha

Background: Brown adipose tissue thermogenic program includes complex molecular and structural changes. However, energetic aspects of this process are poorly depicted. Methods: We investigated time-dependent reprogramming of interscapular brown adipose tissue (IBAT) energy metabolism during cold-acclimation, as well as the effects of nitric oxide ((center dot)NO) on those changes. Rats were exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21. and 45 days, and divided into three groups: control, treated with L-arginine, and treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). Results: In the early phase of cold-acclimation (up to 7 days), the protein levels of all metabolic parameters and oxidative phosphorylation components were below the control. However, metabolic parameters and respiratory chain components entered a new homeostatic level in the late phase of cold-acclimation. These changes were accompanied with increased protein levels of phospho-AMP-dependent protein kinase-alpha (phospho-AMPK alpha) on the first day of cold-acclimation, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) throughout early cold-acclimation. L-arginine positively affected protein expression of enzymes involved in glucose metabolism and beta-oxidation of fatty acids in the early phase of cold-acclimation, and oxidative phosphorylation components throughout cold-acclimation. In contrast, L-NAME had the opposite effects. Conclusion: Results suggest that IBAT structural remodeling is followed by energy metabolism reprogramming, which control might be orchestrated by the action of AMPK alpha and HIF-1 alpha. Data also indicated the involvement of L-arginine-(center dot)NO in the regulation of IBAT metabolism. General significance: Results obtained in this study might be of great importance for elucidating regulatory pathways governing energy metabolism in both physiological and pathophysiological states. (C) 2011 Elsevier B.V. All rights reserved.Ministry of Education and Science of the Republic of Serbia [173055

Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation

This study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N-omega-nitro-L-arginine methyl ester (L-NAME) treated. Compared with controls (22 +/- 1 degrees C), there was an initial increase in the protein level of 5'-AMP-activated protein kinase alpha (day 1), followed by an increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and peroxisome proliferator-activated receptors (PPARs): PPAR alpha and PPAR gamma from day 1 and PPAR delta from day 7 of cold acclimation. Activation of the PGC-1 alpha/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1 alpha/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.Ministry of Education, Science and Technological development of the Republic of Serbia [173054, 173055

Protein expression of ubiquitin in interscapular brown adipose tissue during acclimation of rats to cold: the impact of (NO)-N-center dot

In this study, the effects of l-arginine-nitric-oxide ((NO)-N-a (TM))-producing pathway on protein content of ubiquitin, as an important component of ubiquitin-proteasome system for protein removal, were investigated. We showed that l-arginine markedly decreased ubiquitin protein content in interscapular brown adipose tissue, both in thermogenic inactive (at room temperature) and thermogenic active (on cold) states; while in l-NAME-treated groups this effect was abolished. This result suggests that nitric oxide ((NO)-N-a (TM)), besides well established roles, is involved in this aspect of structure remodeling, as well.Ministry of Education and Science of the Republic of Serbia [173055

Exosomes as bioactive messengers in a critical time for preimplantation embryos n an ultrastructural study

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Regulatory role of PGC-1 alpha/PPAR signaling in skeletal muscle metabolic recruitment during cold acclimation

This study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N-omega-nitro-L-arginine methyl ester (L-NAME) treated. Compared with controls (22 +/- 1 degrees C), there was an initial increase in the protein level of 5'-AMP-activated protein kinase alpha (day 1), followed by an increase in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and peroxisome proliferator-activated receptors (PPARs): PPAR alpha and PPAR gamma from day 1 and PPAR delta from day 7 of cold acclimation. Activation of the PGC-1 alpha/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1 alpha/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.Ministry of Education, Science and Technological development of the Republic of Serbia [173054, 173055

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 capacity undergo the most dramatic changes during both cold acclimation and hibernation, while liver is relatively unaffected by either condition. Additionally, this study provides a basis for further metabolic study that will illuminate the causes of these tissue-specific AD responses, particularly the novel finding of distinct responses by different WAT depots in hibernators. (C) 2013 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia [173055

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 capacity undergo the most dramatic changes during both cold acclimation and hibernation, while liver is relatively unaffected by either condition. Additionally, this study provides a basis for further metabolic study that will illuminate the causes of these tissue-specific AD responses, particularly the novel finding of distinct responses by different WAT depots in hibernators. (C) 2013 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia [173055