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| REVIEW ARTICLE |
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| Year : 2016 | Volume
: 1
| Issue : 1 | Page : 3-13 |
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Fluctuation in ambient temperature: interplay between brown adipose tissue, metabolic health, and cardiovascular diseases
Tse-Yao Wang1, Hua Zhou2, Qinghua Sun3
1 Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, USA
2 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
3 Division of Environmental Health Sciences, College of Public Health, The Ohio State University; Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA
| Date of Web Publication | 14-Apr-2016 |
Correspondence Address:
Qinghua Sun
Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio
USA
 Source of Support: None, Conflict of Interest: None  | Check |
The variations in ambient temperature have been associated with high occurrence of cardiovascular diseases, which is one of the leading global risks for the mortality accounting for 50% of the death in the developed countries. Both heat- and cold-related excess mortalities are mostly attributable to the increase in cardiovascular diseases. Due to the loss of climate system balance caused by increased atmospheric concentration of greenhouse gases, the average global temperatures are expected to rise by 1.1–6.4°C from 1990 to the end of the 21st century. The reinforced intensity, duration, and frequency of heat waves were observed in the past decade with increased average atmosphere and ocean temperature on the Earth. The positive relationship between the heat wave and cardiovascular mortality and morbidity has been demonstrated in the areas with either lower or higher average temperatures. That is, to say, the sudden extreme heat condition lays stress on the cardiovascular system in humans. With a growing body of epidemiological studies, extreme temperature environments and cardiovascular conditions have been increasingly associated. As a class of chronic disorders, the initiation and development of cardiovascular diseases were mainly attributed to metabolic disorders reflecting the prolong stress from obesity, hypertension, hyperglycemia, and hypercholesterolemia whereas the stimulus of sudden temperature change was thought to trigger the onset or worsening of major cardiovascular diseases, which were established by these cumulative risk factors. However, the cold temperature exposure has recently been regarded as a novel therapeutic approach to defense against cardiovascular diseases such as obesity which is resulted from the imbalance between energy intake and energy expenditure. With the chronic mild reduction of ambient temperature, the prevalence and activity of brown adipose tissue (BAT) were upregulated, and the BAT-mediated thermogenesis helps the individual to correct the deviation of energy balance from excess white adipose tissue accumulations. The aim of the present paper was to systematically review the positive and negative effects of the ambient temperature change on cardiovascular diseases, which may lead to new intervention to metabolic health and cardiovascular disease prevention. Keywords: Cardiovascular diseases, fluctuation in ambient temperature, metabolic health
How to cite this article:
Wang TY, Zhou H, Sun Q. Fluctuation in ambient temperature: interplay between brown adipose tissue, metabolic health, and cardiovascular diseases. Environ Dis 2016;1:3-13 |
How to cite this URL:
Wang TY, Zhou H, Sun Q. Fluctuation in ambient temperature: interplay between brown adipose tissue, metabolic health, and cardiovascular diseases. Environ Dis [serial online] 2016 [cited 2023 Mar 30];1:3-13. Available from: http://www.environmentmed.org/text.asp?2016/1/1/3/180334 |
| Heat Waves and Cardiovascular Diseases | |  |
The cardiovascular system involves body temperature regulations by the redistribution of blood flow. When the body temperature rises, cardiovascular system promotes warm blood circulation to the dilated skin vessels and thereby increases the radiation of body heat to the environment. Under extreme hot condition, most of the output that flows from the heart passes through the skin. When body temperature drops, the constricted superficial capillaries limit the blood flow to the skin. Under extreme cold, the vital organs are protected by the extra blood pumped from the heart. To prevent hypo- and hyper-thermia, the complete and healthy cardiovascular system is essential to perform the task requested by autonomic nervous system (ANS). The development of arterial hardness and thickness, as well as endothelial dysfunction, the key features of cardiovascular diseases, is in a slow and complex progress. However, ambient temperature changes may deteriorate vascular injury and therefore accelerate pathogenesis.[1],[2],[3],[4]
Growing epidemiological researches about ambient temperature changes, either increase or decrease, and adverse health effects have been reported since the late 1940s. The effects of global warming driven by increased emission of greenhouse gas and the burst of human population growth since the late 20th century have led to a higher occurrence of heat wave, a period of abnormally hot weather. With the unchecked current rate of greenhouse gas emission, heat waves would cause excess deaths that would climb from around 700 to range between 3000 and 5000 per year by 2050 in the US. The associations between heat waves and mortality have been extensively reported in Europe and North America. Among the heat waves that have occurred in the recent 20 years in the US, the heat wave in July 1995 in Chicago resulted in approximately 750 heat-related deaths. The results from Semenza et al. revealed that the susceptible individuals with chronic cardiovascular diseases lacked the appropriate cardiac compensatory capacity to become acclimated to heat stress.[5] On the other hand, Kaiser et al. emphasized, inter alia, that during the week of July 14, 1995, through July 20, 1995, 443 deaths of excessive heat were reported with an underlying cardiovascular cause.[6] Between June and August 2003, over 70,000 excess deaths were reported across Europe due to record-breaking high temperatures.[7] Austria, Portugal, Spain, Italy, England, Germany, and Switzerland sustained severe heat waves which resulted in an abrupt increase in heat-related mortality.[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] Based on three studies from independent groups, cardiovascular diseases were confirmed to contribute the overall excess mortality during the 2003 European heat wave.[14],[17],[23] In addition to Europe and North America, the increased cardiovascular morbidity and mortality were also observed in Asian cities during their heat waves.[24],[25],[26],[27] The relationship between extreme heat and hospital admissions for cardiovascular diseases is less clear. Although most epidemiological studies in either short-[5],[14],[16],[28],[29] or long-term exposure [25],[30] indicate increased admission rates for cardiovascular diseases by heat wave, no significant increase in morbidity for cardiovascular diseases during the extreme high temperature was detected by two long-term exposure researches that collected the epidemiological data of a 7-year or 12-year period, respectively.[31],[32] However, the higher mortality rate in cardiovascular diseases indicated by both of these two studies may explain the unparalleled increases in hospital admission. The hypothesis that extreme heat triggers rapid occurrence of cardiovascular diseases that may lead to deaths of patients before they get medical attention has been proposed by Mastrangelo et al.[33] The study on rice harvesters exposed to excessive workplace heat may provide a connection between high ambient temperature and cardiovascular dysfunction. When comparing the peak heart rate of the subjects under three different ambient temperatures, 28–30°C, 31–33.5°C, and 35–36°C, significantly higher peak heart rates were observed in the latter two groups. Besides, the subjects from the lower temperature group had faster heart rate recovery than the higher temperature group after cessation of work. Even though the heat stress resulted from heat exposure has been concluded in the study above,[34] the impact of heat waves on specific groups of people, such as the elderly [5],[23],[24],[27],[35],[36],[37] and the people with heart disease history, remained unclear. In the last two decades, increasing frequency of heat waves as an effect of worse global warming resulting in elevated mortality and morbidity of cardiovascular diseases has been demonstrated by an expanding body of investigations. Herein, [Table 1] and [Table 2] list selected investigations of heat waves on cardiovascular diseases in terms of morbidity and mortality in humans, respectively.
| Cold Exposure and Cardiovascular Diseases | | |
Climate and weather factors, such as snow, rain, high wind, and low temperature, may cause hypothermia, a condition in which the individuals experience subnormal body temperature and are unable to maintain normal metabolism and body functions. To prevent the onset of hypothermia, maintaining the core body temperature above 35.0°C (95.0 F) is required. Children, the elderly, and the subjects with certain cardiovascular diseases are at higher risk for hypothermia. Since most deaths in hypothermia are caused by cardiovascular dysfunction, the effects and mechanisms of ambient cold stress on cardiovascular system are of increasing interest. To prevent the dissipation of body heat to ambient cold environment, warm-blooded animals including humans reduce circulation of blood in the peripheral blood vessels. As water flows through a pipe by fixed pressure, volumetric flow rate of blood passing through a vessel driven by constant heart pumping is directly proportional to cross-sectional vessel area. Therefore, peripheral vasoconstriction cuts down the amount of blood flow to the skin and reduces the heat release to the environment under the cold stress. The skin surface cooling burdens, such as increasing in left ventricular preload, blood pressure, and myocardial oxygen demand on cardiovascular system, may lead to the incidence of sudden cardiac arrest and cardiac death, especially in the elderly group.[35],[44],[45],[46],[47],[48],[49],[50],[51] Both short- and long-term meteorological changes in temperature drops are in association with cardiovascular disorders.[52],[53] In short-term temperature reduction, temperature deviated from the average either in winter or in summer is associated with the incidence of cardiovascular events.[54] From the studies related to cold exposure on cardiovascular dysfunction, a 1°C reduction in daily mean temperature was associated with 2.0% and 1.35% increases in myocardial infarction morbidity and cardiovascular mortality, respectively.[55],[56],[57],[58],[59] The prevalence of cardiovascular diseases in winter and cold regions has been described since 1960.[60],[61],[62],[63] During the winter, heavy snowfall, cold temperature, and low atmospheric pressure lead to hypertension, a contributing factor to cardiovascular complications and higher cardiovascular mortality. Constantly elevated blood pressure in response to cold stress has been identified to contribute to the development of hypertension in rodent models.[64],[65],[66],[67],[68],[69] On the other hand, cold stress not only triggers hypertension commencement but also exacerbates the prevalence of hypertension epidemiologically.[70],[71] During the development of hypertension, related comorbidities such as endothelial dysfunction, left ventricular hypertrophy, and accelerated atherosclerotic process contribute to coronary heart disease and cerebrovascular disease (stroke). Thus, the effects of cold spell on cardiovascular mortality in humans are summarized in [Table 3].
There is no doubt that capabilities of heart and vascular system are gradually declining with age, and the aging process is associated with loss of vascular compliance, disorder of vessel resistance, and increased activity of sympathetic nervous system (SNS). The structural changes in the arteries of aged individuals are responsible for the loss of arterial compliance. With age-associated increases in arterial stiffness, the pressor response is further augmented by cold stress in the elderly.[1] In addition to the loss of arterial compliance, resistance vessel vasodilatation and vasoconstriction play a central and pathophysiological role in cerebrovascular resistance [72] and are affected by aging via two homeostatic systems namely L-arginine-NO system and catecholamine α1-adrenergic receptor (AR) system. However, the relationship between age-related decrease in resistance vessel responsiveness and cold stress has yet to be characterized. As a critical component of ANS, SNS is involved in both thermal and cardiovascular homeostasis. The age-related increase in rest SNS activity resulted from the augmented rate of norepinephrine (NE) release into plasma.[73],[74],[75] NE acts as a stress hormone to cause vasoconstriction and increases blood pressure and heart rate under environmental stress. However, chronic age-related NE spillover to plasma is implicated in the pathogenesis of hypertension, which is developed and maintained by cold exposure.[66],[76] Although epidemiological studies refer the elderly to the group of higher morbidity and mortality in cold-induced cardiovascular diseases, further investigations on the mechanism of cold stress to cardiovascular dysfunction in elderly remain needed.
| Cardiovascular Benefits from Cold Exposure | | |
Metabolic disorders and cardiovascular diseases
Cardiovascular disease is a very prevalent chronic condition and is the leading cause of death globally. Two major categories of cardiovascular risk factors have been proposed as modifiable and nonmodifiable risk factors. The risk factors that cannot be changed such as age, gender, race/ethnicity, and family history are so-called nonmodifiable risk factors; however, nevertheless, being aware of and receiving regular checkups for these risk factors can help the prevention of cardiovascular diseases. Managing the modifiable risk factors is critical for preventing, treating, and controlling cardiovascular disease. As we look over the modifiable cardiovascular risk factors including the use of alcohol and tobacco, unhealthy diet, physical inactivity, high cholesterol and lipids, obesity, diabetes, and hypertension, the reciprocal relationship between these risk factors and energy homeostasis has been unmasked. The energy homeostasis can be illustrated by a simple formula: Energy intake = energy expenditure + energy storage. To perfectly keep the energy homeostasis in a balanced status, energy expenditure must meet energy intake. However, unhealthy diet and physical inactivity increase the energy intake and decrease the energy expenditure, respectively, which ultimately leads to high circulating cholesterol levels and obesity, the net result of excess energy storage. Obesity is further predisposing to diabetes and hypertension. To avoid obesity and related cardiovascular diseases, appetite suppressants and physical activities have long been applied as therapeutic approaches to the loss of energy balance by excessive energy intake and poor energy expenditure, respectively. However, several anorectics have been withdrawn from the market due to their adverse drug reactions. Achieving and maintaining regular physical activity with enough intensity to keep sufficient metabolic rate for energy expenditure may not be applicable for specific groups that suffer from obesity.
Rediscovery of brown adipose tissue in adult humans
In 1551, interscapular brown adipose tissue (BAT) was first described in mammals including human.[61] Scientists believe that the disappearance of BAT occurred immediately after infancy in humans. The rediscovery of BAT in adult humans under cold environment has shown therapeutic potential for obesity and related cardiovascular diseases mostly due to the imaging advancement of positron emission tomography-computed tomography (PET/CT). In comparison to white adipose tissue (WAT), the major reservoir for energy in the form of triglycerides, BAT functions for whole body energy expenditure via oxidative metabolism in response to environmental and/or physiological stimuli. With the expression of uncoupling protein 1 (UCP1) on the inner membrane of brown adipocyte mitochondria, adenosine triphosphate synthesis is uncoupled from respiratory electron transport chain into the heat for nonshivering thermogenesis in the cold.[77] As exposed to cold environment, glucose uptake of “active” BAT is around ten times more than the “rest” one in human subjects.[78] Besides glucose disposal, cold exposure promotes BAT-mediated triglyceride clearance to correct hyperlipidemia in mouse models.[79],[80] The huge amount intake of glucose in the interscapular BAT was unintentionally detected by regular [18] F-fluorodeoxyglucose [18] PET/CT scans for cancer patients with metabolically active tumor cells. These false-positive signals were thought to be emitted from muscle cells rather than adipocytes until a decade ago.[81],[82],[83] This uptake in supraclavicular area fat was further confirmed as BAT functionally, physiologically, and genetically.[84],[85],[86] The huge capacity of active BAT to shift the balance between calorie intake and expenditure was reported in both animals and humans under the stress from cold exposure; in another word, cold exposure can manage the obesity, which may be a therapeutic target for cardiovascular diseases.
Sympathetic nervous system on brown adipose tissue thermogenesis
Adaptive thermoregulation of BAT in mammals including both hibernators and nonhibernators has been investigated since the 1960s.[62] During cold exposure, NE released from SNS terminals binds to beta 3-AR (β3-AR) on the surface of brown adipocyte, leading to the stimulation of UCP1 via a cascade of signal transductions involving in cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element binding protein (CREB). Upon NE stimulation, free fatty acids released from lipolysis serve as major substrates for thermogenesis and regulators of UCP1 activity in brown adipocytes. The predominant role of UCP1 in cold-induced thermogenesis is confirmed in UCP1-deficient mouse models.[87],[88],[89] Therefore, the existence of UCP1 is iconic for the thermogenic adipose tissues. The synergism between SNS and thyroid hormones is fundamental in adaptive thermogenesis. Thyroid hormones, triiodothyronine (T3) and thyroxin (T4), are mainly produced by follicular cells in the thyroid gland and involve in systemic energy balance and lipid metabolism. Iodothyronine deiodinases activate thyroid function by transferring T4 to a more active form of thyroid hormone, T3, in different tissues such as liver, kidney, heart, skeletal muscle, CNS, adipose tissue, and thyroid. The conversion of T4 to T3 is performed in BAT by a specific member of deiodinase enzyme subfamily, type II iodothyronine deiodinase (DIO2).[90] Since NE infusion was unable to increase BAT thermal production in hypothyroid rats,[91] hypothyroidism caused the subjects to fail to survive cold exposure.[92] The reduced responsiveness to adrenergic stimulation in hypothyroid rats is due to the deviation of adrenergic signaling pathway of BAT.[93],[94],[95] At the organ level, the SNS activity is modulated by thyroid hormones via AMP-activated protein kinase (AMPK) activity and lipid metabolism in the ventromedial nuclei of hypothalamus. SNS is lined up between thyroid gland and BAT for energy homeostasis. Increased energy expenditure and weight loss are the features of hyperthyroidism which is caused by overproduction of thyroid hormones (T3 and T4).[96],[97] However, the molecular mechanism accounting for the deviated energy homeostasis induced by hyperthyroidism had not been clarified until 2010. As López et al. wrote, “here, we demonstrate that either whole body hyperthyroidism or central administration of T3 decreases the activity of hypothalamic AMPK, increases SNS activity, and upregulates thermogenic markers in BAT.”[98] Based on their pioneer work, the cascade of SNS/NE/β3-AR/BAT thermogenesis is upon the upstream endocrine thyroid. However, the importance of cell-autonomous T3 on BAT differentiation, development, and oxidative capacity was emphasized by conditional DIO2 knockout mouse model (D2KO).[99],[100],[101],[102] DIO2 was important for the enzymatic activity to produce bioactive T3 from T4 resulting in thyroid hormone activation of individual brown adipocyte. In the 1980s, DIO2 was reported to be highly expressed in BAT [90] and the BAT-derived DIO2 was stimulated by SNS.[103] Mice with targeted disruption of DIO2 gene in brown adipocytes are prone to hypothermia under cold stress and are more susceptible to diet-induced obesity due to the impaired embryonic BAT development. The differentiation and development of BAT to exhibit thermogenic proteins including UCP1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and thermoregulation are achieved by DIO2-generated T3 instead of serum T3.[101] Therefore, cold exposure not only activates UCP1-mediated thermogenesis in an individual brown adipocyte (activity state) to maintain normothermia but also results at higher states in hyperplasia (adipocyte number) and hypertrophy (adipocyte size) of thermogenic adipocytes.
Cold stress and beige adipocyte browning
Besides classic BAT, the emergence of beige adipocytes in WAT predominant depots by prolonged cold stimulation is able to achieve hyperplasia of thermogenic adipose tissues. Beige adipocyte, in contrast to the classic interscapular and perirenal brown adipocytes sharing the same progenitor (Myf5+ lineage) with skeletal muscle, comes from a distinct Myf5+ cell lineage. Different genetic models were investigated to clarify the mechanisms involved in the cold-induced beige adipocytes in terms of their development and function. PGC-1α and PR domain containing 16 (PRDM16) are of particular interest because of their critical roles in promoting the “browning” effect in WAT. Under cold stress, quick and high intensity of PGC-1α activation makes itself a dominant regulator of mitochondrial biogenesis and oxidative metabolism. This extreme cold sensitive coactivator is under the control of NE/β3-AR/cAMP/PKA/CREB pathway to induce the expression of UCP1 and enzymes related to mitochondrial respiratory chain. Even though WAT can be equipped with thermogenic features by transgenic expression of PGC-1α[104] and deficiency of PGC-1α ablates the cold-induced thermogenesis in mouse model,[105] no impacts of PGC-1α loss on normal brown fat differentiation have been detected.[106] PRDM16 is a transcriptional factor essential for brown fat phenotypes via induction of PGC-1α and UCP1 expressions and thereby causes the stimulation of uncoupled respiration in response to β3-adrenergic stimulation. Seale et al. and Liu et al. rightly point out that PRDM16 drives PGC-1α and PGC-1β activations by direct protein–protein interactions leading to the browning of the adipose cells in WAT depots and improving whole-body insulin sensitivity and glucose tolerance.[107],[108] The existence of PRDM16 that gives rise to the brown adipocyte identity and suppresses WAT gene expressions is likely to determine the adipocyte fate. As mentioned above, DIO2 is also an applicable thermogenic marker for browning adipocytes. By monitoring the expression level of these thermogenic genes in vitro and in vivo as well as the NE/β3-AR/BAT thermogenesis pathway, the beige cells were reported to be induced by cold exposure in a cell-autonomous manner in addition to NE/β3-AR/cAMP/PKA/CREB axis. The direct cold temperature stimulated thermogenesis occurs in subcutaneous fat but visceral fat and classic BAT.[109] Although both visceral and subcutaneous fat depots were characterized as white adipocytes and play critical role in energy storage and thermic insulation, subcutaneous fat depot has been discovered with substantial thermogenic capacity induced by cold exposure with or without β-AR stimulation. The unique thermogenic response of subcutaneous fat depots to direct cold stress could be explained by their composition and anatomic location. The analysis of the activation of thermogenic program in various cultured adipocytes including beige, white, and brown cell lines concluded that direct cold exposure-induced thermogenic program is specific to white and beige adipocytes which are relatively predominant in subcutaneous fat.[110] In contrast to another white adipocyte-rich visceral fat depot located deeply in the belly, subcutaneous fat depots certainly sense much more fluctuations in environmental temperatures.
Emergence of beige adipocyte
To explain how beige cells are born by cold acclimatization, different hypotheses have been proposed. White-to-brown transdifferentiation processes in adipocytes and scouting of distinct beige adipocyte lineage are actively investigated among the assumptions. Transdifferentiation is defined as a process of converting a mature cell from one differentiated type to another and therefore can bring about the emergence of browning adipocytes in WAT. β3-adrenergic stimulation driven by cold acclimatization plays an important role in white-to-brown adipocyte transdifferentiation in WAT because there is no occurrence of browning cells upon cold stress in β3-adrenoceptor knockout mice; whereas the administration of β3-adrenoceptor agonist promotes the browning phenotypes in normal mice.[111] On the other hand, the plasticity of subcutaneous fat is also explained by the complex in their constituent parts. Under ambient temperature, a specific type of multilocular brown-fat-like cells residing in subcutaneous fat of 129SVE mice was detected without any cold acclimatization. These brown-fat-like cells exhibit intermediate phenotype of thermogenic gene expressions between white and classic brown adipocytes. This beige adipocyte possesses the characteristics of both white and brown adipocytes regarding function and molecular properties. However, the features toward classic BAT thermogenesis are significantly induced upon cAMP stimulation.[112] The de novo adipogenesis from the precursor cell to beige adipocyte in subcutaneous fat depot was further proved by AdipoChaser mouse developed by Wang et al.[113] The prevalent of beige cells either from white-to-brown transdifferentiation or distinct subgroup of precursor cells provides high physiological plasticity of WAT in subcutaneous fat, which is definitely a target for metabolic defects.
Modalities to nonshivering thermogenesis
Due to the fundamental role of NE/β3-AR/cAMP/PKA/CREB axis in cold-induced thermogenesis, sympathomimetic drugs have been thought of potential remedies for metabolic complications. However, systemic application of β-agonist isoprenaline does not activate BAT in humans even though the energy expenditure is elevated to the same extent as exposed to cold stress.[114] In addition, ephedrine, a classic agonist of NE at ARs, fails to induce BAT thermogenesis in humans.[115] Since β-adrenergic compounds are inadequate to therapeutic needs in metabolic disorders, the modalities other than pharmacological agents have been proposed. Exercise,[116],[117] electrical stimulation,[118] and cold exposure have gained interest as physical stimuli to active BAT thermogenesis. The benefits of exercise on skeletal muscle in BAT thermogenesis come from PGC-1α-mediated irisin production. Irisin is a hormone cleaved and secreted from membrane FNDC5 protein in the skeletal muscle. Both exercise training and overexpression of PGC-1α induce irisin production leading to the browning of white adipocytes and improved systemic metabolism in mouse model.[116] However, according to human genomic DNA analysis and unchanged FNDC5 mRNA expression in response to exercise in human subjects, the beneficial effect of irisin observed in mice is unlikely translated to clinical application.[119] Establishing electrical field to stimulate NE released from sympathetic nerves is proved to induce BAT thermogenesis,[118] but intensive investigations for this novel physical modality on BAT thermogenesis are rarely described. Cold as a stimulus to induce nonshivering thermogenesis was observed in rodents in the 1950s,[120],[121],[122] and BAT was believed to be the main site of nonshivering thermogenesis by cold from the 1960s based on the discoveries of Smith et al.[60],[61],[123],[124] The initial experiments to induce nonshivering thermogenesis were mostly performed under harsh conditions of high intensity of cold stress (~4°C) and prolonged cold exposure (>2 weeks) in rodents. However, short-term (<24 h) of 4°C cold exposure is able to alter lipoprotein profile [79] and mild cold exposure is sufficient to induce UCP1-mediated BAT activation in both rodent models and human subjects.[125],[126],[127] Thermal neutral zone, a range of ambient temperatures to minimize the loss of metabolic body heat production to the external environment, is widely accepted at 25–27°C of ambient temperature to naked adults, mild cold exposures ranged from 14 to 19°C immediately increase UCP1 expression, BAT thermogenesis, and related metabolic benefit in humans.[78],[115],[127],[128],[129],[130],[131],[132],[133] Compared to the cold exposure for a short period but in high intensity, mild and prolonged cold exposure leading to BAT thermogenesis provide a practicable basis for treatment of obesity and metabolic diseases. It is evident from recent studies that a mild reduction of ambient temperature (19°C) is able to increase human BAT activity and corresponding lipolysis and energy expenditure.[126],[127] The population increased in obesity, which are paralleled to gradual increased thermal exposures of indoor temperatures, could be taken as presumptive evidence of the effects of mild cold exposure in BAT thermogenesis and energy expenditure.[128]
| Conclusion | | |
This review examined the fluctuations in ambient temperature to cardiovascular diseases and the benefit effects of mild reduction of ambient temperature in terms of energy expenditure and obesity and related complications [Figure 1]. It is evident from epidemiologic studies that there is an increase of impacts on morbidity and mortality of cardiovascular diseases during extreme weather in western countries in the recent decades. As a result, newly established evaluation criteria might help ensure effective and efficient weather warning system. In Asian regions, both short- and long-term researches examining the impact of extreme temperatures on morbidity and mortality have been launched recently. However, these studies were only in small scales and focused on limited cities in Korea and China.[25],[26],[124],[125],[126],[127],[128],[129],[130],[131],[132],[133],[134],[135],[136],[137] Therefore, future studies to better define and classify etiologies contributing to extreme ambient temperature-related morbidity and mortality in Asian areas are needed and would be helpful in planning preventive strategies for vulnerable populations such as children, the elderly, and the subjects with cardiovascular diseases. | Figure 1: Schematic summary illustrating ambient temperature changes on human health and disease development via adipose tissues. “Brown” means brown adipose tissue while “white” means white adipose tissue. “+” represents promotion/increase while “–” represents inhibition/decrease
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The association of obesity with the development and deterioration of cardiovascular diseases, which lead to the vulnerability during the extreme weather events, has been widely investigated, and different therapeutic targeting obesity-mediated heart diseases have been proposed. The mechanisms of BAT thermogenesis in energy homeostasis have made great strides in the recent years with a growing body of in vitro and in vivo studies, which suggests mild cold exposure as a potential physical modality against obesity and related heart complications. However, although the latest findings support mild reduction of environmental temperature for reducing obesity, metabolic syndrome, and cardiovascular disease via BAT thermogenesis, the optimization of mild cold intervention might need to be achieved by further clinical trials.
Financial support and sponsorship
This work was supported by NIH grant ES018900 to Dr. Sun.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1], [Table 2], [Table 3]
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