scholarly journals Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation

2019 ◽  
Vol 20 (10) ◽  
pp. 2456 ◽  
Author(s):  
Huanyu Lu ◽  
Shan Tang ◽  
Chong Xue ◽  
Ying Liu ◽  
Jiye Wang ◽  
...  
Keyword(s):  
Cold Stress ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Cold Adaptation ◽  
Therapeutic Strategy ◽  
Erk Signaling ◽  
Lipid Trafficking ◽  
Brown Adipose ◽  
White Fat ◽  
Harsh Conditions

Cold exposure stress causes hypothermia, cognitive impairment, liver injury, and cardiovascular diseases, thereby increasing morbidity and mortality. Paradoxically, cold acclimation is believed to confer metabolic improvement to allow individuals to adapt to cold, harsh conditions and to protect them from cold stress-induced diseases. However, the therapeutic strategy to enhance cold acclimation remains less studied. Here, we demonstrate that the mitochondrial-derived peptide MOTS-c efficiently promotes cold adaptation. Following cold exposure, the improvement of adipose non-shivering thermogenesis facilitated cold adaptation. MOTS-c, a newly identified peptide, is secreted by mitochondria. In this study, we observed that the level of MOTS-c in serum decreased after cold stress. MOTS-c treatment enhanced cold tolerance and reduced lipid trafficking to the liver. In addition, MOTS-c dramatically upregulated brown adipose tissue (BAT) thermogenic gene expression and increased white fat “browning”. This effect might have been mediated by MOTS-c-activated phosphorylation of the ERK signaling pathway. The inhibition of ERK signaling disturbed the up-regulatory effect of MOTS-c on thermogenesis. In summary, our results indicate that MOTS-c treatment is a potential therapeutic strategy for defending against cold stress by increasing the adipose thermogenesis via the ERK pathway.

scholarly journals miR-31-5p regulates cold acclimation of the wood-boring beetle Monochamus alternatus via ascaroside signaling

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bin Zhang ◽  
Lilin Zhao ◽  
Jing Ning ◽  
Jacob D. Wickham ◽  
Haokai Tian ◽  
...  
Keyword(s):  
Cold Stress ◽  
Cold Acclimation ◽  
Cold Adaptation ◽  
Cold Hardiness ◽  
Expression Patterns ◽  
Specific Gene ◽  
Metabolic Depression ◽  
Monochamus Alternatus ◽  
Freeze Avoidance ◽  
Thermal Plasticity

Abstract Background Survival to cold stress in insects living in temperate environments requires the deployment of strategies that lead to physiological changes involved in freeze tolerance or freeze avoidance. These strategies may consist of, for instance, the induction of metabolic depression, accumulation of cryoprotectants, or the production of antifreeze proteins, however, little is known about the way such mechanisms are regulated and the signals involved in their activation. Ascarosides are signaling molecules usually known to regulate nematode behavior and development, whose expression was recently found to relate to thermal plasticity in the Japanese pine sawyer beetle Monochamus alternatus. Accumulating evidence also points to miRNAs as another class of regulators differentially expressed in response to cold stress, which are predicted to target genes involved in cold adaptation of insects. Here, we demonstrate a novel pathway involved in insect cold acclimation, through miRNA-mediated regulation of ascaroside function. Results We initially discovered that experimental cold acclimation can enhance the beetle’s cold hardiness. Through screening and functional verification, we found miR-31-5p, upregulated under cold stress, significantly contributes to this enhancement. Mechanistically, miR-31-5p promotes production of an ascaroside (asc-C9) in the beetle by negatively targeting the rate-limiting enzyme, acyl-CoA oxidase in peroxisomal β-oxidation cycles. Feeding experiments with synthetic asc-C9 suggests it may serve as a signal to promote cold acclimation through metabolic depression and accumulation of cryoprotectants with specific gene expression patterns. Conclusions Our results point to important roles of miRNA-mediated regulation of ascaroside function in insect cold adaptation. This enhanced cold tolerance may allow higher survival of M. alternatus in winter and be pivotal in shaping its wide distribution range, greatly expanding the threat of pine wilt disease, and thus can also inspire the development of ascaroside-based pest management strategies.

scholarly journals Thyroid hyperactivity with high thyroglobulin in serum despite sufficient iodine intake in chronic cold adaptation in an Arctic Inuit hunter population

2012 ◽  
Vol 166 (3) ◽  
pp. 433-440 ◽  
Author(s):  
Stig Andersen ◽  
Kent Kleinschmidt ◽  
Bodil Hvingel ◽  
Peter Laurberg
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Cold Exposure ◽  
Cold Adaptation ◽  
Urinary Iodine ◽  
Thyroid Activity ◽  
East Greenland ◽  
Brown Adipose ◽  
Iodine Excretion ◽  
The Impact

ObjectiveAdult man hosts brown adipose tissue with the capacity to consume energy and dissipate heat. This is essential for non-shivering thermogenesis and its activation depends on sympathetic activity and thyroid hormones. This led us to evaluate the impact of chronic cold exposure on thyroid activity and thyroid hormones in serum in Arctic residents.DesignComparative, population-based study (n=535) performed in Greenland.MethodsHunters were compared with other men, and Inuit in remote settlements in East Greenland with no modern housing facilities were compared with the residents of the capital city in West Greenland and residents of a major town in East Greenland in a cross-sectional study. We used interview-based questionnaires, measured TSH, free thyroxine, free triiodothyronine (fT3), thyroglobulin (TG) antibody and TG (a measure of thyroid activity) in serum, and iodine and creatinine in spot urine samples.ResultsSerum TG was the highest among hunters (P=0.009) and settlement dwellers (P=0.001), who were most markedly exposed to cold, even though they had the highest urinary iodine excretion (hunters,P<0.001; settlement dwellers,P<0.001). Hunters and settlement dwellers also had the lowest fT3(hunters,P<0.001; settlement dwellers,P<0.001) after adjusting for gender, age, smoking habits, alcohol intake and iodine excretion in multivariate linear regression models. TSH was not influenced by measures of cold exposure (hunter,P=0.36; residence,P=0.91).ConclusionsCold exposure influenced thyroid hormones and TG in serum in Arctic populations consistent with consumption of thyroid hormone and higher thyroid hormone turnover. Findings emphasise that changes in thyroid activity are essential in cold adaptation in Arctic residents.

Effect of cold acclimation on neuromuscular function of the hand

2006 ◽  
Vol 31 (4) ◽  
pp. 480-481
Author(s):  
Carla L.M. Geurts
Keyword(s):  
Cold Stress ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Force Control ◽  
Cold Water ◽  
Water Immersion ◽  
Temperature Response ◽  
Neuromuscular Function ◽  
Cold Water Immersion ◽  
Hand Temperature

The research in this thesis investigated the effects of cold stress on neuromuscular function with the main focus on cold acclimation. In total, 6 studies, 1 field study and 5 experiments, were conducted. The field study showed that during manual work in cold weather, finger and hand temperature can drop to levels that may impair manual function. The first 2 experiments were conducted to investigate the effect of acute local cold stress on force control and to investigate the effect of cold-induced vasodilatation (CIVD) on neuromuscular function. In experiment 1, it was found that cooling of the hand in 10 °C cold water for 10 min did not improve force control, although neuromuscular function was significantly impaired after cooling. In experiment 2, cold-induced vasodilatation, occurring after 20 min of 8 °C cold-water immersion of the hand, was confined to the finger tip and had no effect on the temperature of the first dorsal interosseus (FDI) muscle or its neuromuscular function. A series of cold acclimation studies was conducted to investigate the effect of repeated cold-water hand immersions on neuromuscular function. In these experiments, neuromuscular function was tested before and after 2–3 weeks of daily hand immersion in 8 °C cold water for 30 min. In experiment 3, it was found that 3 weeks of cold-water immersion resulted in a decrease in minimum and mean index finger temperature and CIVD was attenuated. Neuromuscular function was not affected by this change in temperature response. In experiment 4, one hand was exposed daily to cold water and compared with the opposite control hand. Blood plasma catecholamine concentrations were increased after 2 weeks in the cold-exposed hand, but no changes in temperature response or neuromuscular function were found after repeated cold exposure. Thermal comfort after 30 min of cold-water immersion significantly improved after repeated cold exposure causing a discrepancy between actual and perceived temperature and it was suggested that this may impose a greater risk of cold injury owing to a change in behavioural thermoregulation. In the last experiment, core temperature was elevated by bicycling at a submaximal level during the cold hand immersion. Exercise had a direct effect on the temperature response during cold-water immersion, decreasing the minimum FDI temperature and slowing down the deteriorating effect of cold on neuromuscular function; however, exercise showed was no effect on local cold acclimation. It is concluded that local repeated cold exposures may improve finger and hand temperature and subjective thermal ratings, but that these changes are too small to improve neuromuscular function. The best remedy to maintain manual function is to limit or avoid cold stress as much as possible. If sufficient protection of the hands is impossible, core heating through exercise or passive heating may be a solution.

Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats

2003 ◽  
Vol 95 (4) ◽  
pp. 1584-1590 ◽  
Author(s):  
Angel A. Zaninovich ◽  
Inés Rebagliati ◽  
Marcela Raíces ◽  
Conrado Ricci ◽  
Karl Hagmüller
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Mitochondrial Respiration ◽  
Mitochondrial Oxygen Consumption ◽  
Normal Body ◽  
Thyroid Ablation ◽  
Brown Adipose

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.

Thyroid hormone-catecholamine interrelationship during cold acclimation in rats Compensatory role of catecholamine for altered thyroid states

1986 ◽  
Vol 113 (4) ◽  
pp. 536-542 ◽  
Author(s):  
Tamotu Sato ◽  
Eiichi Imura ◽  
Akisato Murata ◽  
Noboru Igarashi
Keyword(s):  
Thyroid Hormone ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Plasma Membranes ◽  
Body Weight Gain ◽  
The Body ◽  
Hormone Deficiency ◽  
Adult Rats ◽  
Liver Plasma Membranes ◽  
Brown Adipose

Abstract. Effects of hyper- and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5°C) and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU-treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine β-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P <0.01 vs controls). T4-treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and [3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, 1) thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and 2) the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency.

scholarly journals Biomarkers of Browning in Cold Exposed Siberian Adults

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2162
Author(s):  
Agrafena Efremova ◽  
Georgia Colleluori ◽  
Mikhail Thomsky ◽  
Jessica Perugini ◽  
Marina Protasoni ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Exposed Group ◽  
Anthropometric Parameters ◽  
Cold Temperatures ◽  
Bat Activity ◽  
Fat Depots ◽  
Brown Adipose ◽  
White Fat

Cold-exposure promotes energy expenditure by inducing brown adipose tissue (BAT) thermogenesis, which over time, is also sustained by browning, the appearance, or increase, of brown-like cells into white fat depots. Identification of circulating markers reflecting BAT activity and browning is crucial to study this phenomenon and its triggers, also holding possible implications for the therapy of obesity and metabolic diseases. Using RT-qPCR, we evaluated the peripheral blood mononuclear cells (PBMC) expression profile of regulators of BAT activity (CIDEA, PRDM16), white adipocytes browning (HOXC9 and SLC27A1), and fatty acid β-oxidation (CPT1A) in 150 Siberian healthy miners living at extremely cold temperatures compared to 29 healthy subjects living in thermoneutral conditions. Anthropometric parameters, glucose, and lipid profiles were also assessed. The cold-exposed group showed significantly lower weight, BMI, hip circumference, and PBMC expression of CIDEA, but higher expression of HOXC9 and higher circulating glucose compared to controls. Within the cold-exposed group, BMI, total cholesterol, and the atherogenic coefficient were lower in individuals exposed to low temperatures for a longer time. In conclusion, human PBMC expresses the brown adipocytes marker CIDEA and the browning marker HOXC9, which, varying according to cold-exposure, possibly reflect changes in BAT activation and white fat browning.

Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure

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 ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Soleus Muscle ◽  
Cold Exposure ◽  
Skeletal Muscles ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose

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.

Glycerokinase activity in brown adipose tissue: a sympathetic regulation?

2002 ◽  
Vol 282 (4) ◽  
pp. R1185-R1190 ◽  
Author(s):  
N. H. Kawashita ◽  
W. T. L. Festuccia ◽  
M. N. Brito ◽  
M. A. F. Moura ◽  
S. R. C. Brito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Cold Exposure ◽  
Turnover Rates ◽  
Physiological Conditions ◽  
Balanced Diet ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Sympathetic Regulation

The effect of brown adipose tissue (BAT) sympathetic hemidenervation on the activity of glycerokinase (GyK) was investigated in different physiological conditions. In rats fed a balanced diet, the activity of the enzyme was ∼50% lower in BAT-denervated pads than in intact, innervated pads. In rats adapted to a high-protein, carbohydrate-free diet, norepinephrine turnover rates and BAT GyK activity were already reduced, and BAT denervation resulted in a further decrease in the activity of the enzyme. Cold acclimation of normally fed rats at 4°C for 10 days markedly increased the activity of the enzyme. Cold exposure (4°C) for 6 h was insufficient to stimulate BAT GyK, but the activity of the enzyme was already increased after 12 h of cold exposure. The cold-induced BAT GyK stimulation was completely blocked in BAT-denervated pads. The data indicate that an adequate sympathetic flow to BAT is required for the maintenance of normal levels of GyK activity and for the enzyme response to situations, such as cold exposure, which markedly increase BAT sympathetic flow.

scholarly journals Cold Tolerance in Hypothyroid Rabbits: Role of Skeletal Muscle Mitochondria and Sarcoplasmic Reticulum Ca2+ ATPase Isoform 1 Heat Production

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6262-6271 ◽  
Author(s):  
Ana Paula Arruda ◽  
Luisa A. Ketzer ◽  
Mariana Nigro ◽  
Antonio Galina ◽  
Denise P. Carvalho ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cold Acclimation ◽  
Cold Tolerance ◽  
Heat Production ◽  
Cold Exposure ◽  
Muscle Enzymes ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Brown Adipose

Brown adipose tissue (BAT) is involved in rat and mice thermoregulation, and heat produced by BAT depends on the concerted action of thyroid hormones and catecholamines. Little is known about cold-induced thermogenesis in mammals that have little or no BAT, such as rabbits. In these animals, thermogenesis primarily occurs in skeletal muscle. In this work, we have studied the effect of cold acclimation (4 C for 10 d) in normal and hypothyroid rabbits. It is known that hypothyroid rats die after a few hours of cold exposure. We now show that, different from rats, hypothyroid rabbits sustain their body temperature and survive after 10 d cold exposure. When compared with rabbits kept at room temperature, the muscles of cold-exposed rabbits showed a dark red color characteristic of oxidative muscle fibers. According to this pattern, we observed that in both normal and hypothyroid rabbits, cold exposure promotes an increase in oxygen consumption by skeletal muscle mitochondria. Moreover, in red muscle, cold acclimation induces an increase in the expression and activity of sarcoplasmic reticulum Ca2+ ATPase isoform 1 (SERCA1), one of the muscle enzymes involved in heat production. We conclude that rabbit cold tolerance is probably related to increased muscle oxidative metabolism and heat production by SERCA1 and that these changes are not completely dependent on normal thyroid function.

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