Glucose uptake, glucose transporter GLUT4, and glycolytic enzymes in brown adipose tissue from rats adapted to a high-protein diet

doi:10.1053/meta.2002.35582

Metabolism

Volume 51, Issue 11, November 2002, Pages 1501-1505

https://doi.org/10.1053/meta.2002.35582 Get rights and content

Abstract

In vivo rates of glucose uptake, insulin-responsive glucose transporter (GLUT4) content, and activities of glycolytic enzymes were determined in brown adipose tissue (BAT) from rats adapted to a high-protein, carbohydrate-free (HP) diet. Adaptation to the HP diet resulted in marked decreases in BAT glucose uptake and in GLUT4 content. Replacement of the HP diet by a balanced control diet for 24 hours restored BAT glucose uptake to levels above those in rats fed the control diet, with no changes in GLUT4 levels in 4 of 5 animals examined. BAT denervation of rats fed the control diet induced a 50% reduction in glucose uptake, but did not significantly affect the already markedly reduced BAT hexose uptake in HP diet-fed rats. It is suggested that the pronounced decrease in BAT glucose uptake in these animals is due to the combined effects of the HP diet-induced reductions in plasma insulin levels and in BAT sympathetic activity. Adaptation to the HP diet was accompanied by decreased activities of hexokinase, phosphofructo-1-kinase, and pyruvate kinase (PK). The activity of BAT PK in HP diet-fed rats was reduced to about 50% of controls, and approached normal levels 24 hours after diet reversion. BAT denervation induced a small (15%) decrease in BAT PK activity in control rats, but did not affect the activity of the enzyme in HP diet-adapted rats. Also, denervation did not interfere with the restoration of PK activity induced by diet substitution. Treatment with anti-insulin serum resulted in an almost 50% reduction in PK activity in both innervated and denervated BAT from rats fed the control diet, but caused a much smaller ([thkap ]20%) decrease in BAT from HP diet-fed rats. Furthermore, anti-insulin serum administration completely suppressed the restoration of BAT PK activity induced by diet reversion. These data suggest that, differently from glucose uptake, BAT PK activity is predominantly controlled by hormonal/metabolic factors.

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Citation Excerpt :
This is further confirmed by decreased expression of two key glycolytic genes, Gapdh and Hk1, and of Glut4, which facilitates cellular glucose uptake. A decreased activity of key glycolytic enzymes and a decrease in GLUT4 content have been previously reported as an adaptation to an HP diet in other tissues, such as brown adipose tissue [62]. In addition, two other genes involved in lipid metabolism/adipogenesis were affected in PBMCs as a result of the intake of an HP diet, Dhrs3 and Pref-1.
Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4 months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.
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The procedure and the technique for NE measurement have been described in detail [20]. The procedure, which was based on the method of Sokoloff et al [21] and modified by Ferré et al [22], has been previously described [23]. Briefly, 30 μCi (11 Ci/mmol) of 2-deoxy-1-[14 C]glucose (2-DG) in 0.5 mL of 0.9% NaCl was injected intravenously, and serial blood samples were collected to determine the concentrations of glucose and 2-DG (in terms of radioactivity).
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^☆: Supported by grants from the Funda[ccedil][atilde]o de Amparo [agrave] Pesquisa do Estado de S[atilde]o Paulo (FAPESP no. 01/10050-8) and Conselho Nacional de Desenvolvimento Cient[iacute]fico e Tecnol[oacute]gico (CNPq no. 510923/93-3)

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Glucose uptake, glucose transporter GLUT4, and glycolytic enzymes in brown adipose tissue from rats adapted to a high-protein diet☆

Abstract