scholarly journals 14-3-3ζ mediates an alternative, non-thermogenic mechanism to reduce heat loss and improve cold tolerance

2019 ◽  
Author(s):  
Kadidia Diallo ◽  
Sylvie Dussault ◽  
Christophe Noll ◽  
Angel F. Lopez ◽  
Alain Rivard ◽  
...  

SummaryFollowing prolonged cold exposure, adaptive thermogenic pathways are activated to maintain homeothermy, and elevations in body temperature are generally associated with UCP1-dependent and -independent increases in energy expenditure. One of the earliest, identified functions of the molecular scaffold, 14-3-3ζ, was its role in the synthesis of norepinephrine, a key endogenous factor that stimulates thermogenesis. This suggests that 14-3-3ζ may have critical roles in cold-induced thermogenesis. Herein, we report that transgenic over-expression of TAP-14-3-3ζ in mice significantly improved tolerance to prolonged cold. When compared to wildtype controls, TAP mice displayed significantly elevated body temperatures and paradoxical decreases in energy expenditure. No changes in β-adrenergic sensitivity or oxidative metabolism were observed; instead, 14-3-3ζ over-expression significantly decreased thermal conductance via increased peripheral vasoconstriction. These findings suggest 14-3-3ζ mediates alternative, non-thermogenic mechanisms to mitigate heat loss for homeothermy. Our results point to an unexpected role of 14-3-3ζ in the regulation of body temperature.Graphical abstract

1991 ◽  
Vol 69 (7) ◽  
pp. 1842-1847 ◽  
Author(s):  
Gregory K. Snyder ◽  
Joseph R. Coelho ◽  
Dalan R. Jensen

In chicks the ability to regulate body temperature to adult levels develops during the first 2 weeks of life. We examined whether the ability of young chicks to regulate body temperature is increased by elevated levels of the thyroid hormone 3,3′5-triiodothyronine. By 13 days following hatch, body temperatures of chicks were not significantly different from those expected for adult birds. Furthermore, at an ambient temperature of 10 °C, 13-day-old control chicks were able to maintain body temperature, and elevated serum thyroid hormone levels did not increase rates of oxygen consumption or body temperature above control values. Six-day-old chicks had body temperatures that were significantly lower than those of the 13-day-old chicks and were not able to regulate body temperature when exposed to an ambient temperature of 10 °C. On the other hand, 6-day-old chicks with elevated serum thyroid hormone had significantly higher rates of oxygen consumption than 6-day-old control chicks, and were able to maintain constant body temperatures during cold exposure. The increased oxygen consumption rates and improved ability to regulate body temperature during cold exposure were correlated with increased citrate synthase activity in skeletal muscle. Our results support the argument that thyroid hormones play an important role in the development of thermoregulatory ability in neonate birds by stimulating enzyme activities associated with aerobic metabolism.


1959 ◽  
Vol 14 (1) ◽  
pp. 43-45 ◽  
Author(s):  
M. B. Kreider ◽  
P. F. Iampietro ◽  
E. R. Buskirk ◽  
David E. Bass

Effects of continuous cold stress on 24-hour patterns of body temperature were studied in five men. Cold stress consisted in living at 15.6℃ (60℉) for 14 days wearing only shorts. The cold period was preceded and followed by 2 weeks at 26.7℃ (80℉). Activity (minimal) and diet were the same for all periods. One blanket was used at night. Rectal temperature (Tr) and skin temperature (Ts) were measured. Tr during sleep fell more rapidly and to lower values during cold exposure (35.6℃) than during the control period (36.1℃). Ts during sleep was slightly lower in the cold than in the control period; also, Ts did not exhibit the gradual drop characteristic of sleep in the control period. Comparison of Tr and Ts between early and later cold days revealed the following differences: a) nocturnal Tr fell to lower levels on the later cold days; b) nocturnal toe temperatures were 15℃ (27℉) higher on the later cold days. The arch temperatures followed the same pattern as the toes. No significant differences were found in daytime temperatures between early and later cold days. The data suggest that evidence for acclimatization to cold in terms of altered body temperature responses may be fruitfully sought in responses during rewarming and/or sleep. Submitted on September 19, 1958


1978 ◽  
Vol 56 (4) ◽  
pp. 571-577 ◽  
Author(s):  
D. L. Jones ◽  
W. L. Veale ◽  
K. E. Cooper

Alterations of the ionic constituents of solutions perfused through the tissue of the posterior hypothalamic region in conscious cats elicited changes in body temperatures. Increasing the [Ca2+] to [Na+] ratio of the perfusion solution elicited falls in body temperature which were accompanied by changes in posture and vasomotor tone which assisted the heat loss. The magnitude of the fall was dependent on the ratio of [Ca2+] to [Na+] and was not related to the osmolarity of perfusion solution. The addition of dextrose to the perfusion solution attenuated or abolished the response produced by an increase in the [Ca2+] to [Na+] ratio. This dextrose effect could be attributed to its role as an energy substrate. These data are consistent with and extend previous suggestions that the set point for body temperature may be dependent on the inherent ratio of the ionic constituents of the posterior hypothalamic area. Further, they suggest that these ionically induced alterations can be overriden by increasing the available energy substrate.


1982 ◽  
Vol 62 (1) ◽  
pp. 123-132 ◽  
Author(s):  
V. A. GREGG ◽  
L. P. MILLIGAN

The role of Na+, K+-ATPase in the energy expenditure of sheep skeletal muscle and the influence of exposure to cold on this role were studied. An in vitro preparation of muscle was developed that achieved O2 availability and a functional membrane potential. A 10−6 M concentration of ouabain yielded a maximum inhibition of respiration of 38.9 ± 1.8% using muscle preparations from a random group of sheep. Whole body and muscle O2 consumptions and ouabain-sensitive muscle respiration were measured for warm- and cold-exposed sheep fed at maintenance or 1150 g of alfalfa pellets per day. Cold exposure increased whole body and muscle O2 consumption. Inhibition of respiration by ouabain was 37.6 ± 1.2% and 41.0 ± 3.6% for warm- and cold-exposed sheep fed at maintenance, and 28.5 ± 4.0% and 45.0 ± 4.0% for warm- and cold-exposed sheep fed 1150 g of alfalfa pellets per day. The increase in the ouabain-sensitive component of respiration accounted for 48–79% of the increased O2 consumption of muscle from cold-exposed sheep. It was concluded that the Na+, K+-ATPase of sheep muscle is a major means of energy expenditure and has an important role in the increased thermogenesis resulting from cold exposure. Key words: Skeletal muscle, Energy expenditure, muscle respiration, cold thermogenesis, sodium-potassium transport


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jennifer Wootton Hill ◽  
Iyad H Manaserh

Abstract The important role of astrocytes in the central control of energy balance and glucose homeostasis has only recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (IR) in astrocytes (IRKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IRKOGFAP mice displayed a significant decrease in energy expenditure and a striking decrease in basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. Brown adipose tissue in IRKOGFAP mice exhibited increased adipocyte size, more apoptosis, loss of innervation, and decreased βAR3 expression levels. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.


2014 ◽  
Vol 54 (9) ◽  
pp. 1497 ◽  
Author(s):  
S. A. McCoard ◽  
H. V. Henderson ◽  
F. W. Knol ◽  
S. K. Dowling ◽  
J. R. Webster

The combination of heat generation and reducing heat loss from the skin surface is important for maintaining core body temperature in a neonate. Thermogenesis studies traditionally focus on measurement of core body temperature but not the contribution of radiated heat loss at the skin surface. This study aimed to evaluate the utility of using thermal imaging to measure radiated heat loss in newborn lambs. Continuous thermal images of newborn lambs were captured for 30 min each during the baseline (11−18°C), cold-exposure (0°C) and recovery (11−18°C) periods by using an infrared camera. Core body temperature measured by rectal thermometer was also recorded at the end of each period. In all, 7 of the 10 lambs evaluated had reduced rectal temperatures (0.4−1°C) between the baseline and recovery periods, while three maintained body temperature despite cold exposure. During the baseline period, infrared heat loss was relatively stable, followed by a rapid decrease of 5°C within 5 min of cold exposure. Heat loss continued to decrease linearly in the cold-exposure period by a further 10°C, but increased rapidly to baseline levels during the recovery period. A temperature change of between 20°C and 35°C was observed during the study, which was likely to be due to changes in vasoconstriction in the skin to conserve heat. The present study has highlighted the sensitivity of infrared thermal imaging to estimate heat loss from the skin in the newborn lamb and shown that rapid changes in heat loss occur in response to cold exposure.


1982 ◽  
Vol 243 (1) ◽  
pp. R70-R76
Author(s):  
M. L. Laudenslager ◽  
H. J. Carlisle ◽  
S. E. Calvano

The role of the thyroid in the mediation of an estrogen-associated change in thermal balance was studied in thyroidectomized and in propylthiouracil-treated ovariectomized rats. Prior to propylthiouracil treatment, estrogen-treated ovariectomized rats and intact female rats had higher rates of heat production and dry heat loss at -5 degrees C than ovariectomized rats. Heat production of estrogen-treated and intact female rats was well below their rates of dry heat loss without an alteration in the absolute rate of heat loss in the hypothyroid condition. Heat production exceeded heat loss only in the hypothyroid ovariectomized group not receiving estrogen. Ovariectomized rats without estrogen maintained thermal balance, whereas rectal temperatures fell in both intact and estrogen-treated ovariectomized rats during cold exposure. Increased heat loss unbalanced by heat production was also observed in surgically thyroidectomized estrogen-treated ovariectomized rats tested at -5 degrees C. These results suggest that an estrogen-induced increase in heat loss, which is compensated by an increase in heat production in the euthyroid but not the hypothyroid condition, is one mechanism responsible for estrogen-associated changes in thermal balance during cold exposure.


Endocrinology ◽  
2019 ◽  
Vol 160 (4) ◽  
pp. 863-879 ◽  
Author(s):  
Isin Cakir ◽  
Myriam Diaz-Martinez ◽  
Pauline Lining Pan ◽  
E Brian Welch ◽  
Sachin Patel ◽  
...  

Abstract Leptin signals to regulate food intake and energy expenditure under conditions of normative energy homeostasis. The central expression and function of leptin receptor B (LepRb) have been extensively studied during the past two decades; however, the mechanisms by which LepRb signaling dysregulation contributes to the pathophysiology of obesity remains unclear. The paraventricular nucleus of the hypothalamus (PVN) plays a crucial role in regulating energy balance as well as the neuroendocrine axes. The role of LepRb expression in the PVN in regard to the regulation of physiological function of leptin has been controversial. The single-minded homolog 1 gene (Sim1) is densely expressed in the PVN and in parts of the amygdala, making Sim1-Cre mice a useful model for examining molecular mechanisms regulating PVN function. In this study, we characterized the physiological role of LepRb in Sim1-expressing neurons using LepRb-floxed × Sim1-Cre mice. Sim1-specific LepRb-deficient mice were surprisingly hypophagic on regular chow but gained more weight upon exposure to a high-fat diet than did their control littermates. We show that Sim1-specific deletion of a single LepRb gene copy caused decreased surface and core body temperatures as well as decreased energy expenditure in ambient room temperatures in both female and male mice. Furthermore, cold-induced adaptive (nonshivering) thermogenesis is disrupted in homozygous knockout mice. A defective thermoregulatory response was associated with defective cold-induced upregulation of uncoupling protein 1 in brown adipose tissue and reduced serum T4. Our study provides novel functional evidence supporting LepRb signaling in Sim1 neurons in the regulation of body weight, core body temperature, and cold-induced adaptive thermogenesis.


1986 ◽  
Vol 251 (6) ◽  
pp. R1118-R1125
Author(s):  
T. J. Bartness ◽  
C. J. Billington ◽  
A. S. Levine ◽  
J. E. Morley ◽  
N. E. Rowland ◽  
...  

The role of insulin in metabolic efficiency (ME, i.e., efficiency of body wt gain) was examined under conditions of maximal energy expenditure in control and diabetic rats. Long-lasting insulin was administered using a protocol that did not affect food intake and increased ME in both groups. Half the animals were injected chronically with norepinephrine (NE). NE alone in controls decreased body weight and ME and increased brown adipose tissue (BAT) growth, thermogenic potential [cytochrome c oxidase activity (COA)], and lipoprotein lipases (LPL) activity; however, in diabetics, body weight, ME, and food intake all decreased and only BAT LPL activity and DNA content increased. The combination of NE and insulin increased BAT protein and COA in diabetics; in controls, all BAT measures were further increased and ME was intermediate to that of either treatment alone. Cold exposure decreased body weight and ME, increased food intake and qualitatively produced similar increases in BAT growth, COA, and LPL activity in both controls and diabetics. In diabetics, combined cold exposure and insulin did not affect the increase in BAT growth or LPL activity resulting from either treatment alone, but in controls this combination decreased BAT growth and COA. It is concluded that, even under conditions of maximal energy expenditure, both extremes of basal insulin status result in decreased BAT growth and thermogenic potential, but have opposite effects on ME.


2020 ◽  
Vol 247 (1) ◽  
pp. 39-52
Author(s):  
Iyad H Manaserh ◽  
Emily Maly ◽  
Marziyeh Jahromi ◽  
Lakshmikanth Chikkamenahalli ◽  
Joshua Park ◽  
...  

The important role of astrocytes in the central control of energy balance and glucose homeostasis has recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (Ir) in astrocytes (IrKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IrKOGFAP mice displayed significantly lower energy expenditure and a strikingly lower basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. IrKOGFAP mice displayed sex differences in metabolic function and thermogenesis that may contribute to the development of obesity and type II diabetes as early as 2 months of age. While brown adipose tissue exhibited higher adipocyte size in both sexes, more apoptosis was seen in IrKOGFAP males. Less innervation and lower BAR3 expression levels were also observed in IrKOGFAP brown adipose tissue. These effects have not been reported in models of astrocyte Ir deletion in adulthood. In contrast, body weight and glucose regulatory defects phenocopied such models. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.


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