A Dramatic Accumulation of Glycogen in the Brown Adipose Tissue of Rats Following Recovery from Cold Exposure

doi:10.1006/abbi.1999.1157

Archives of Biochemistry and Biophysics

Volume 365, Issue 1, 1 May 1999, Pages 54-61

https://doi.org/10.1006/abbi.1999.1157 Get rights and content

Abstract

In a morphological study of brown adipose tissue (BAT) of rats returned after exposure to cold (+5°C) to neutral temperature (+25°C), striking periodic acid Schiff staining was observed, indicating substantial glycogen accumulation. Enzymatic analysis revealed that the glycogen content increased from the 4.05 ± 0.51 (μmol glucose unit per gram of tissue, mean ± SE) control value to 57.3 ± 9.66 when the animals were returned to neutral temperature for 24 h after a 1-week cold period. Glycogen repletion was also observed in liver and skeletal muscle; however, the glycogen levels in these tissues never exceeded the control values. The accumulation of glycogen in the BAT started by the 3rd hour of replacement and peaked by the 24th hour. This glycogen was readily utilized during the next short cold exposure of the animals. The plasma leptin concentration was reduced at the cold temperature. The hexokinase II activity in the BAT increased to 29.3 ± 1.46 vs the 11.8 ± 1.06 control (mU/mg protein ± SE) after a 1-week cold exposure and this level was maintained during the return to neutral temperature. The total glycogen synthetase (GStot) and the glycogen synthetaseaactivity also increased after a 1-week cold exposure and increased further during the replacement. The level of GStot reached 26.9 ± 1.39 vs 9.54 ± 1.43 control by the 24th hour of replacement. At the same time, the glycogen phosphorylaseaactivity declined during the replacement. The concentration of glucose 6-phosphate (an activator of GS) decreased in the cold but returned to normal during the replacement. These changes in the BAT are in favor of glycogen synthesis.

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Citation Excerpt :
Consistent with this, gene enrichment analysis indicated the enhancement of glycogen metabolism in WT mice. Previous studies have demonstrated that BAT accumulates significant amounts of glycogen, although the effect of cold exposure on glycogen synthesis is controversial [42–44]. It is possible that the enhancement of glycogen synthesis occurs subsequent to enhanced glucose uptake, as glucose-derived G-6-P activates glycogen synthase via allosteric binding [45].
Brown adipose tissue (BAT) is a site of metabolic thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1) and represents a target for a therapeutic intervention in obesity. Cold exposure activates UCP1-mediated thermogenesis in BAT and causes drastic changes in glucose, lipid, and amino acid metabolism; however, the relationship between these metabolic changes and UCP1-mediated thermogenesis is not fully understood.
We conducted metabolomic and GeneChip array analyses of BAT after 4-h exposure to cold temperature (10 °C) in wild-type (WT) and UCP1-KO mice.
Cold exposure largely increased metabolites of the glycolysis pathway and lactic acid levels in WT, but not in UCP1-KO, mice, indicating that aerobic glycolysis is enhanced as a consequence of UCP1-mediated thermogenesis. GeneChip array analysis of BAT revealed that there were 2865 genes upregulated by cold exposure in WT mice, and 838 of these were upregulated and 74 were downregulated in UCP1-KO mice. Pathway analysis revealed the enrichment of genes involved in fatty acid (FA) β oxidation and triglyceride (TG) synthesis in both WT and UCP1-KO mice, suggesting that these metabolic pathways were enhanced by cold exposure independently of UCP1-mediated thermogenesis. FA and cholesterol biosynthesis pathways were enhanced only in UCP1-KO mice. Cold exposure also significantly increased the BAT content of proline, tryptophan, and phenylalanine amino acids in both WT and UCP1-KO mice. In WT mice, cold exposure significantly increased glutamine content and enhanced the expression of genes related to glutamine metabolism. Surprisingly, aspartate was almost completely depleted after cold exposure in UCP1-KO mice. Gene expression analysis suggested that aspartate was actively utilized after cold exposure both in WT and UCP1-KO mice, but it was replenished from intracellular N-acetyl-aspartate in WT mice.
These results revealed that cold exposure induces UCP1-mediated thermogenesis-dependent glucose utilization and UCP1-independent active lipid metabolism in BAT. In addition, cold exposure largely affects amino acid metabolism in BAT, especially UCP1-dependently enhances glutamine utilization. These results contribute a comprehensive understanding of UCP1-mediated thermogenesis-dependent and thermogenesis-independent metabolism in BAT.
Effects of stanniocalcin hormones on rat brown adipose tissue metabolism under fed and fasted conditions
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Citation Excerpt :
However, hSTC-2 decreased markedly the glycogen concentration in BAT from fed rats, maintaining lactate levels and glucose oxidation capacity in this organ. Significant amounts of glycogen are stored in the BAT, which seems to be an important source of glucose during non-shivering thermogenesis, as evidenced by the rise in glycogen utilization in rats exposed to cold (Farkas et al., 1999; Festuccia et al., 2011; Jakus et al., 2008). During thermogenesis, significant amounts of glucose are converted to lactate by anaerobic glycolysis, producing ATP (Festuccia et al., 2011).
In this study we determined the effect of fed and fasting (48 h) states on the expression of stanniocalcin-1 (Stc1) and stanniocalcin-2 (Stc2) in rat brown adipose tissue (BAT), as well as the in vitro effects of human stanniocalcin 1 and 2 (hSTC-1 and hSTC-2) hormones on lipid and glucose metabolism. In addition, lactate, glycogen levels and hexokinase (HK) activity were determined. In fasting Stc2 expression increased markedly. The targets of action of hSTC-1 and hSTC-2 were glucose uptake and oxidation as well as glycogen storage, controlling the energetic metabolism in BAT. The reduction in glycogen concentration induced by hSTC-2 in fed state might have deleterious consequences in BAT, such as decreased thermogenic activity, FA esterification and other adipocyte functions. On the other hand, the increase of glucose uptake caused by hSTC-1 of fed rats could play a role as a plasma glucose-clearing hormone in the postprandial period.
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Citation Excerpt :
Indeed, the huge amount of glycogen accumulated in the BAT of reacclimated rats disappears when the animals are reexposed to cold for 30 min (6).
Rats were exposed to cold and then reacclimated at neutral temperature. Changes related to fatty acid and glucose metabolism in brown and white adipose tissues (BAT and WAT) and in muscle were then examined. Of the many proteins involved in the metabolic response, two lipogenic enzymes, acetyl-coenzyme A carboxylase (ACC) and ATP-citrate lyase, were found to play a pervasive role and studied in detail. Expression of the total and phosphorylated forms of both lipogenic enzymes in response to cold increased in BAT but decreased in WAT. Importantly, in BAT, only the phosphorylation of the ACC1 isoenzyme was enhanced, whereas that of ACC2 remained unchanged. The activities of these enzymes and the in vivo rate of FFA synthesis together suggested that WAT supplies BAT with FFA and glucose by decreasing its own synthetic activity. Furthermore, cold increased the glucose uptake of BAT by stimulating the expression of components of the insulin signaling cascade, as observed by the enhanced expression and phosphorylation of Akt and GSK-3. In muscle, these changes were observed only during reacclimation, when serum insulin also increased. Such changes may be responsible for the extreme glycogen accumulation in the BAT of rats reacclimated from cold.
Adaptive changes in interscapular brown adipose tissue during reacclimation after cold: The role of redox regulation
2007, Journal of Thermal Biology
- 1.
  The level of antioxidative defence, intensity of sympathetic innervation, expression of uncoupling protein 1 (UCP1), and ultrastructure of interscapular brown adipose tissue (IBAT) were studied in rats acclimated to room (22±1 °C), low temperature (4±1 °C, 45 days) and during reacclimation to 22 °C (days 1, 3, and 7).
- 2.
  The cold-induced increase in catalase, glutathione peroxidase, glutathione reductase, thioredoxin reductase, as well as a decrease in the activities of CuZn- and Mn-superoxide dismutases, shows specific dynamics of restitution during reacclimation to 22 °C.
- 3.
  The intensity of the cold-induced enhancement of the sympathetic innervation and UCP1 expression gradually decreases during reacclimation to 22 °C, but with the seventh day level still higher compared to the animals acclimated to room temperature.
- 4.
  Electron-microscopy study of IBAT shows that changes of the strongly activated tissue in cold undergo gradual restitution during reacclimation to 22 °C, but are observed already on the first day through a massive accumulation of glycogen, accompanied by a change in the lipid profile.

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^☆: Milton, A. S.

¹: To whom correspondence should be addressed at Department of Biochemistry, University Medical School, Szigeti ut 12, Pecs H-7624, Hungary. Fax: +36-72-326-466. E-mail:[email protected].

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Regular ArticleA Dramatic Accumulation of Glycogen in the Brown Adipose Tissue of Rats Following Recovery from Cold Exposure☆

Abstract

Biochim. Biophys. Res. Commun.

Temperature Regulation: Recent Physiological and Pharmacological Advances

Nature

Nature

Int. J. Dev. Biol.

Am. J. Physiol.

Int. J. Obes.

FASEB J.

Proc. Nutr. Soc.

Annu. Rev. Nutr.

J. Biol. Chem.

Acta Biochim. Biophys. Acad. Sci. Hung.

Anal. Biochem.

Eur. J. Biochem.

Anal. Biochem.

Regular Article
A Dramatic Accumulation of Glycogen in the Brown Adipose Tissue of Rats Following Recovery from Cold Exposure☆