Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues

1990 ◽  
Vol 259 (5) ◽  
pp. R1043-R1049 ◽  
Author(s):  
A. L. Vallerand ◽  
F. Perusse ◽  
L. J. Bukowiecki

The effects of cold exposure on the net rates of 2-[3H]deoxy-D-glucose uptake (Ki) in rat peripheral tissues were investigated comparatively in warm- and cold-acclimated animals to determine whether cold acclimation induces regulatory alterations in glucose metabolism. Acute exposure of warm-acclimated (25 degrees C) rats to cold (48 h at 5 degrees C) markedly increased the Ki values in red and white skeletal muscles (2-5 times), in the heart (8 times), in several white adipose tissue (WAT) depots (4-20 times), and in brown adipose tissue (BAT) (110 times). After cold acclimation (3 wk at 5 degrees C), the Ki values further increased in the heart (15 times) and WAT (up to 29 times) but decreased in BAT (36 times). Remarkably, glucose uptake was still increased in muscles of cold-exposed/cold-acclimated animals (that do not shiver), demonstrating that enhanced glucose uptake may occur in muscles in the absence of shivering thermogenesis (or contractile activity). When cold-acclimated rats were returned to the warm for 18 h, the Ki values of all tissues, except WAT, returned to control levels. Cold exposure synergistically potentiated the stimulation of tissue glucose uptake induced by a maximal effective dose of insulin (0.5 U/kg iv) in warm- as well as in cold-acclimated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

1987 ◽  
Vol 253 (2) ◽  
pp. E179-E186 ◽  
Author(s):  
A. L. Vallerand ◽  
F. Perusse ◽  
L. J. Bukowiecki

The effects of cold exposure (48 h at 4 degrees C) and insulin injection (0.5 U/kg iv) on the rates of net 2-[3H]deoxyglucose uptake (Ki) in peripheral tissues were investigated in warm-acclimated rats (25 degrees C). Cold exposure and insulin treatment independently increased Ki values in skeletal muscles (soleus, extensor digitorum longus, and vastus lateralis), heart, white adipose tissue (subcutaneous, gonadal, and retroperitoneal), and brown adipose tissue (P less than 0.01). The effects of cold exposure were particularly evident in brown adipose tissue where the Ki increased greater than 100 times. When the two treatments were combined (insulin injection in cold-exposed rats), it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an "insulin-like" effect on Ki that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.


1994 ◽  
Vol 266 (3) ◽  
pp. R914-R920 ◽  
Author(s):  
X. Liu ◽  
F. Perusse ◽  
L. J. Bukowiecki

Cold exposure activates the sympathetic nervous system and markedly stimulates glucose uptake in rat peripheral tissues [A. L. Vallerand, F. Perusse, and L. J. Bukowiecki. Am. J. Physiol 259 (Regulatory Integrative Comp. Physiol. 28): R1043-R1049, 1990]. To test whether norepinephrine (NE) mimics the effects of cold exposure, we estimated the effects of chronic NE treatment on tissue glucose uptake by determining the glucose metabolic index using the 2-[1,2-3H(N)]deoxy-D-glucose method. NE was administered in conscious rats at various doses (ranging from 1.9 to 25.1 nmol.kg-1.min-1) during 4 days via minipumps implanted subcutaneously. At doses > 10 nmol.kg-1.min-1, NE maximally stimulated glucose uptake in interscapular brown adipose tissue (approximately 50 times above controls) and epididymal white adipose tissue (approximately 3 times above controls). NE infusion (18.8 nmol.kg-1.min-1) increased the circulating levels of NE from 1.1 +/- 0.1 to 19.2 +/- 0.4 nM (P < 0.001), which is in the range of concentrations for the stimulatory effects of NE on glucose uptake in isolated brown adipocytes. At all concentrations tested, NE infusion did not stimulate glucose uptake in the heart and skeletal muscles. NE treatment did not significantly alter plasma insulin or glucose levels but increased the concentration of circulating free fatty acids. The capacity of brown adipose tissue for NE stimulation of glucose uptake (expressed per g of tissue) was much higher than that of white adipose tissue (100 times), various types of white or red skeletal muscles (10-80 times), or the heart (3-4 times).(ABSTRACT TRUNCATED AT 250 WORDS)


2014 ◽  
Vol 307 (11) ◽  
pp. E1020-E1029 ◽  
Author(s):  
Ruy A. Louzada ◽  
Maria C. S. Santos ◽  
João Paulo A. Cavalcanti-de-Albuquerque ◽  
Igor F. Rangel ◽  
Andrea C. F. Ferreira ◽  
...  

During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1α genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation.


1989 ◽  
Vol 257 (1) ◽  
pp. R96-R101 ◽  
Author(s):  
H. Shibata ◽  
F. Perusse ◽  
A. Vallerand ◽  
L. J. Bukowiecki

The effects of fasting and cold exposure on glucose uptake in skeletal muscles (tibialis anterior, quadriceps, and soleus), heart, and brown adipose tissue (BAT) were studied in conscious rats. Glucose uptake was estimated by determining the glucose metabolic index of individual tissues using the 2-[3H]deoxyglucose method. Fasting for 18 h at 25 degrees C decreased plasma glucose levels (-40%) and glucose uptake in heart (-95%) and skeletal muscles (-64-90%) but did not significantly affect glucose uptake in BAT. Fasting for 48 h did not further decrease these parameters. On the other hand, cold exposure (48 h at 5 degrees C) of fed animals did not alter plasma glucose levels but increased glucose uptake in heart (73%), skeletal muscles (126-326%), and particularly in BAT (95-fold). Remarkably, cold exposure stimulated glucose uptake in BAT and skeletal muscles of 18-h fasted rats by the same order of magnitude as in fed animals (percentagewise), thereby indicating that glucose represents an essential metabolite for shivering (muscles) and nonshivering (BAT) thermogeneses. In the heart of starved animals, the cold-induced increase in glucose uptake was even more important (8-fold) than in fed animals. Considering that cold exposure of fasted rats results in a severe insulinopenia, it is suggested that cold exposure stimulates glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways.


1991 ◽  
Vol 261 (3) ◽  
pp. E298-E303 ◽  
Author(s):  
M. Sudo ◽  
Y. Minokoshi ◽  
T. Shimazu

Effects of electrical and chemical stimulation of the ventromedial (VMH) and lateral hypothalamic (LH) nuclei on glucose uptake in peripheral tissues were studied by the 2-deoxy-D-[3H]glucose (2-[3H]DG) method in anesthetized rats. Electrical stimulation of the VMH increased the rate constant of glucose uptake in brown adipose tissue (BAT; 8 times), heart (3 times), and skeletal muscles (1.5 times) but not in white adipose tissue, diaphragm, and brain, without detectable changes in plasma insulin levels. Chemical stimulation of the VMH by microinjection of L-glutamate also enhanced the rate constant of glucose uptake in BAT, heart, and skeletal muscles preferentially, which indicates that the enhancement of glucose uptake in these tissues is derived from activation of VMH neurons. The increased rate of glucose uptake in BAT in response to VMH stimulation was effectively suppressed by surgical sympathetic denervation, suggesting a mediation of the sympathetic nerve in this effect. On the other hand, electrical stimulation of the LH had no appreciable effect on 2-[3H]DG uptake in any tissues. It is concluded that glucose uptake in certain peripheral tissues is accelerated selectively by activation of VMH neurons, the action of which is independent of plasma insulin but which is probably via the sympathetic nervous system.


1988 ◽  
Vol 252 (3) ◽  
pp. 843-849 ◽  
Author(s):  
F J López-Soriano ◽  
J A Fernández-López ◽  
T Mampel ◽  
F Villarroya ◽  
R Iglesias ◽  
...  

The net uptake/release of glucose, lactate and amino acids from the bloodstream by the interscapular brown adipose tissue of control, cold-exposed and cold-acclimated rats was estimated by measurement of arteriovenous differences in their concentrations. In the control animals amino acids contributed little to the overall energetic needs of the tissue; glucose uptake was more than compensated by lactate efflux. Cold-exposure resulted in an enhancement of amino acid utilization and of glucose uptake, with high lactate efflux. There was a net glycine and proline efflux that partly compensated the positive nitrogen balance of the tissue; amino acids accounted for about one-third of the energy supplied by glucose to the tissue. Cold-acclimation resulted in a very high increase in glucose uptake, with a parallel decrease in lactate efflux and amino acid consumption. Branched-chain amino acids, however, were more actively utilized. This was related with a much higher alanine efflux, in addition to that of glycine and proline. It is suggested that most of the glucose used during cold-exposure is returned to the bloodstream as lactate under conditions of active lipid utilization, amino acids contributing their skeletons largely in anaplerotic pathways. On the other hand, cold-acclimation resulted in an important enhancement of glucose utilization, with lowered amino acid oxidation. Amino acids are thus used as metabolic substrates by the brown adipose tissue of rats under conditions of relatively scarce substrate availability, but mainly as anaplerotic substrates, in parallel to glucose. Cold-acclimation results in a shift of the main substrates used in thermogenesis from lipid to glucose, with a much lower need for amino acids.


1993 ◽  
Vol 264 (6) ◽  
pp. E890-E895 ◽  
Author(s):  
Y. Shimizu ◽  
H. Nikami ◽  
K. Tsukazaki ◽  
U. F. Machado ◽  
H. Yano ◽  
...  

Cold exposure has been shown to increase glucose uptake specifically in brown adipose tissue (BAT), the major site for sympathetically controlled metabolic heat production. In this study, the relationship between glucose uptake and glucose transporters (GLUT) was examined in rats exposed to cold for various periods. To minimize the stimulatory effect of circulating insulin, all animals were starved for 20-24 h before the measurements. Acute (4 h) cold exposure had no effect on protein and mRNA levels of GLUT-4, the predominant isoform of GLUT in BAT, despite a significant increase in cellular glucose uptake. Prolonged (1-10 days) cold exposure produced a parallel increase in GLUT-4 expression and glucose uptake in BAT. In contrast, cold exposure had no noticeable effect on GLUT-1, another isoform of GLUT in BAT, and on GLUT-4 in other insulin-sensitive tissues such as white adipose tissue and muscles. The increased glucose uptake and GLUT-4 expression were completely abolished after surgical sympathetic denervation. These findings suggest that cold exposure increases glucose uptake in BAT by at least two distinct mechanisms, both of which are dependent on sympathetic nerve: 1) an increase in the amount of GLUT-4 due to the stimulation of its de novo synthesis, and 2) an increase without stimulation of GLUT synthesis, probably due to the change in the transport activity of GLUT-4 and/or its translocation from an intracellular pool to the plasma membrane.


2020 ◽  
Vol 41 (07) ◽  
pp. 427-442
Author(s):  
Alexandra R. Martin ◽  
Soonkyu Chung ◽  
Karsten Koehler

AbstractExercise is commonly utilized for weight loss, yet research has focused less on specific modifications to adipose tissue metabolism. White adipose tissue (WAT) is the storage form of fat, whereas brown adipose tissue (BAT) is a thermogenic tissue whose uncoupling increases energy expenditure. The most established BAT activator is cold exposure, which also transforms WAT into “beige cells” that express uncoupling protein 1 (UCP1). Preliminary evidence in rodents suggests exercise elicits similar effects. The purpose of this review is to parallel and examine differences between exercise and cold exposure on BAT activation and beige induction. Like cold exposure, exercise stimulates the sympathetic nervous system and activates molecular pathways responsible for BAT/beige activation, including upregulation of BAT activation markers (UCP1, proliferator-activated receptor-gamma coactivator-1α) and stimulation of endocrine activators (fibroblast growth factor-21, irisin, and natriuretic peptides). Further, certain BAT activators are altered exclusively by exercise (interleukin-6, lactate). Markers of BAT activation increase from both cold exposure and exercise, whereas effects in WAT are compartment-specific. Stimulation of endocrine activators depends on numerous factors, including stimulus intensity and duration. Evidence of these analogous, albeit not mirrored, mechanisms is demonstrated by increases in adipose activity in rodents, while effects remain challenging to quantify in humans.


2003 ◽  
Vol 95 (4) ◽  
pp. 1584-1590 ◽  
Author(s):  
Angel A. Zaninovich ◽  
Inés Rebagliati ◽  
Marcela Raíces ◽  
Conrado Ricci ◽  
Karl Hagmüller

The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4°C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24°C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of β- and α1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3′-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.


Sign in / Sign up

Export Citation Format

Share Document