Mild Cold Research Articles

Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men

In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 °C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid (18FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues.

Protective Role of Hypothermia Against Heat Stress in Differentiated and Undifferentiated Human Neural Precursor Cells: A Differential Approach for the Treatment of Traumatic Brain Injury

Introduction:The present study aimed to explore protective mechanisms of hypothermia against mild cold and heat stress on highly proliferative homogeneous human Neural Precursor Cells (NPCs) derived from Subventricular Zone (SVZ) of human fetal brain.Methods:CD133+ve enriched undifferentiated and differentiated human NPCs were exposed to heat stress at 42°C. Then, Western-blot quantification was performed using Hsp-70 (70 kilodalton heat shock proteins) recombinant protein. Finally, changes in pluripotency and Hsp-70 expression were measured using immunofluorescence staining and RT-qPCR (Quantitative reverse transcription PCR) analysis, respectively.Results:Heat stress resulted in abnormal neurospheres development. The apoptosis rate was enhanced during long-term in vitro culture of neurospheres. Neurogenic differentiation reduced and showed aberrent phenotypes during heat stress. After hypothermia treatment significant improvement in neurospheres and neuronal cell morphology was observed.Conclusion:Mild-hypothermia treatment induces attenuated heat shock response against heat stress resulting in induced HSP-70 expression that significantly improves structure and function of both undifferentiated human NPCs and differentiated neurons.

Thermal comfort sustained by cold protective clothing in Arctic open-pit mining-a thermal manikin and questionnaire study.

Workers in the Arctic open-pit mines are exposed to harsh weather conditions. Employers are required to provide protective clothing for workers. This can be the outer layer, but sometimes also inner or middle layers are provided. This study aimed to determine how Arctic open-pit miners protect themselves against cold and the sufficiency, and the selection criteria of the garments. Workers’ cold experiences and the clothing in four Arctic open-pit mines in Finland, Sweden, Norway and Russia were evaluated by a questionnaire (n=1,323). Basic thermal insulation (Icl) of the reported clothing was estimated (ISO 9920). The Icl of clothing from the mines were also measured by thermal manikin (standing/walking) in 0.3 and 4.0 m/s wind. The questionnaire showed that the Icl of the selected clothing was on average 1.2 and 1.5 clo in mild (−5 to +5°C) and dry cold (−20 to −10°C) conditions, respectively. The Icl of the clothing measured by thermal manikin was 1.9–2.3 clo. The results show that the Arctic open-pit miners’ selected their clothing based on occupational (time outdoors), environmental (temperature, wind, moisture) and individual factors (cold sensitivity, general health). However, the selected clothing was not sufficient to prevent cooling completely at ambient temperatures below −10°C.

Effects of cardboard bed on sleep onset period under mild cold exposure

Effects of cardboard bed on sleep onset period under mild cold exposure

Finger pulp reconstruction with innervated reverse digital artery flap through bilateral neurorrhaphy

Objective To investigate the clinical outcomes of finger pulp reconstruction with innervated reverse digital artery flap with the sensory nerve branches through bilateral neurorrhaphy. Methods From April 2014 to March 2015, innervated reverse digital artery flaps with the sensory branches of proper digital nerves were transferred to repair pulp defects of 17 fingers in 15 patients. The flap was designed at the lateral aspect of the proximal phalanx. Two branches of the proper digital nerve that projected towards the flap were included in the flap. After flap inset, these two branches were coapted with the stumps of the bilateral proper digital nerves. Results All the flaps and skin grafts survived uneventfully. These cases were follow-up for 7 to 11 months. The reconstructed pulps had good appearance and supple texture. There was no flap bulkiness or pigmentation. The involved fingers recovered normal active motion. The pain and temperature sensation were recovered in all the flaps. Static two-point discrimination value was 5 to 8 mm, while the average Semmes-Weinstein monofilament score was 3.22 to 3.84. The average Cold Intolerance Severity Score(CISS) was 23 (range, 11 to 44), with 15 patients corresponded to mild cold intolerance and 2 patients corresponded to moderate cold intolerance. According to the upper limb functional assessment criteria issued by the Chinese Hand Surgery Society, the results were rated as excellent in 14 fingers, good in 2 fingers, and fair in 1 finger. Conclusion Satisfactory appearance and sensation of finger pulp can be restored by transferring innervated reverse digital artery island flap with bilateral neurorrhaphy to the branches of the proper digital nerves. Key words: Surgical flaps; Finger injuries; Treatment outcome; Neurorrhaphy

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults.

Recent work in rodents has demonstrated that basal activity of the local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown adipose tissue (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT in lean young adults. Methods: Twenty adult lean normal subjects (10 women and 10 men; mean age ± SD, 23.3 ± 3.8 y; body mass index, 23.7 ± 2.5 kg/m2) underwent 11C-meta-hydroxyephedrin (11C-HED) and 15O-water PET imaging at rest and after exposure to mild cold (16°C) temperature. In addition, 18F-FDG images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into 2 groups (high BAT and low BAT) based on the presence of 18F-FDG tracer uptake. Blood flow and 11C-HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT and WAT. Whole-body daily energy expenditure (DEE) during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO2) was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results:18F-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 ± 37 g; low-BAT, 16 ± 4 g). 11C-HED RI under thermoneutral conditions significantly predicted 18F-FDG uptake during cold stress (R2 = 0.68, P < 0.01). In contrast to the significant increase of 11C-HED RI during cold in BAT (2.42 ± 0.85 vs. 3.43 ± 0.93, P = 0.02), cold exposure decreased the 11C-HED RI in WAT (0.44 ± 0.22 vs. 0.41 ± 0.18) as a consequence of decreased perfusion (1.22 ± 0.20 vs. 1.12 ± 0.16 mL/100 g/min). The contribution of WAT to whole-body DEE was approximately 150 kcal/d at rest (149 ± 52 kcal/d), which decreased to approximately 100 kcal/d during cold (102 ± 47 kcal/d). Conclusion: The level of sympathetic innervation, as determined by 11C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of 11C-HED RI and 18F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and 18F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat.

Determination of thermal comfort zone for early-stage broilers

Environmental temperatures currently considered within comfort zone for broiler rearing may be misleading or even obsolete from actual values. Some factors such as animal genetics, nutrition and poultry management, mainly acclimatization to tropical and subtropical conditions, influence in determining the comfort zone for birds. This study aimed to evaluate the effects of five different thermal environments on animal welfare and rearing performance of broiler chickens, setting an ideal temperature range (comfort zone) for each of the first three weeks of poultry breeding. The chicks (375) were randomly placed into five climatic chambers set to distinct thermal conditions, being: one as recommended by the literature, another as stated by Cassuce and the other three at different levels of apparent cold stress (mild, moderate and severe). The findings showed that best poultry performance and ideal comfort indices (based on Black Globe Humidity and Temperature Index) were achieved within a temperature range between mild cold and Cassuce comfort temperature, rather than those previously reported in the literature.

Short-term cold exposure modulates human VLDL and HDL metabolism

Objectives: Upon cold activation, brown adipose tissue (BAT) combusts intracellular triglycerides (TG) into heat. Mouse studies showed that BAT consequently internalizes VLDL-TG-derived fatty acids to replenish intracellular TG stores (Hoeke, Circ Res 2016). Since the effect of cold-induced BAT activation on human lipoprotein metabolism remained elusive, we now assessed the effect of short-term mild cold exposure on the lipoprotein profile in men.

Theory and Design of Counter Flow Shell-and-Coil Heat Exchanger for CO2Based Solar Water Heater

A shell type helical tube countercurrent flow heat exchanger was designed, fabricated and tested using CO2 refrigerant material. Helical copper tube was immersed in bulk water tank. Hot CO2 was piped to upper coil baffle and cold CO2 was circulated into collector loop through lower baffle. Cold water was made to enter through lower tap and hot water was taken out from upper tap. Both in/out pipes were inserted from the top and coil tubes from upper and lower sides of water tank. Supercritical thermosyphon operation was achieved by evacuated glass tube solar heat collector using CO2 refrigerant. U shaped copper pipes enveloped in aluminum foil were inserted in evacuated glass tubes to transfer heat under thermosiphon principle to upper header connected to inlet baffle of shell type helical coil heat exchanger. Lower header was connected to heat exchanger helical coil outlet baffle. Solar collector heat raised CO2 refrigerant temperature from 35 to 78C giving temperature difference of 43C. Temperature of CO2 refrigerant at exit from heat exchanger was found to be 40C at surrounding ambient temperature of 36C. Heat exchanger raised the inlet water temperature from 26 to 55C under off water tap condition in about 3 hours. Inlet and outlet temperature difference of heat exchanger was measured to be 27C. We believe system efficiency can further increase if we use the system in mild sunshine cold weather regions duplicating geothermal loop.

Metapneumovirus Infections and Respiratory Complications.

Acute respiratory tract infections (ARTIs) are the most common illnesses experienced by people of all ages worldwide. In 2001, a new respiratory pathogen called human metapneumovirus (hMPV) was identified in respiratory secretions. hMPV is an RNA virus of the Paramyxoviridae family, and it has been isolated on every continent and from individuals of all ages. hMPV causes 7 to 19% of all cases of ARTIs in both hospitalized and outpatient children, and the rate of detection in adults is approximately 3%. Symptoms of hMPV infection range from a mild cold to a severe disease requiring a ventilator and cardiovascular support. The main risk factors for severe disease upon hMPV infection are the presence of a high viral load, coinfection with other agents (especially human respiratory syncytial virus), being between 0 and 5 months old or older than 65 years, and immunodeficiency. Currently, available treatments for hMPV infections are only supportive, and antiviral drugs are employed in cases of severe disease as a last resort. Ribavirin and immunoglobulins have been used in some patients, but the real efficacy of these treatments is unclear. At present, the direction of research on therapy for hMPV infection is toward the development of new approaches, and a variety of vaccination strategies are being explored and tested in animal models. However, further studies are required to define the best treatment and prevention strategies.

Hospitalizations from Hypertensive Diseases, Diabetes, and Arrhythmia in Relation to Low and High Temperatures: Population-Based Study.

Little is known about the extent to which ambient temperatures contribute to the burden of hospitalizations from hypertensive diseases, diabetes, and arrhythmia. To fill this knowledge gap, we conducted a time-series study comprising entire population of Ontario, Canada during 1996–2013. A distributed lag non-linear model was developed to estimate the cumulative effect of temperatures over a 21-day lag period. We computed the burden of hospitalizations attributable to cold and heat. Furthermore, we separated the burden into components related to mild and extreme temperatures. Compared to the temperature with minimum risk of morbidity, cold temperatures (1st percentile) were associated with a 37% (95% confidence interval: 5%, 78%) increase in hypertension-related hospitalizations whereas no significant association with hot temperatures (99th percentile) was observed. Cold and hot temperatures were also associated with a 12% (1%, 24%) and a 30% (6%, 58%) increase in diabetes-related hospitalizations, respectively. Arrhythmia was not linked to temperatures. These estimates translate into ~10% of hypertension-related hospitalizations attributable to total cold, and ~9% from mild cold. Similarly, ~11% of diabetes-related hospitalizations were due to total heat, virtually all of which were from mild heat. In conclusion, ambient temperatures, especially in moderate ranges, contribute to excess hospitalizations from hypertension and diabetes.

Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation

SummaryThe discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased 18fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C–17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health.

Fine-tuning of eTRPM8 expression and activity conditions keratinocyte fate

ABSTRACTRecently, we reported the cloning and characterization of short isoform of the icilin-activated cold receptor TRPM8 channel in keratinocytes, dubbed eTRPM8. We demonstrated that eTRPM8 via fine tuning of the endoplasmic reticulum (ER) – mitochondria Ca2+ shuttling regulates mitochondrial ATP and superoxide (O2•-) production and, thereby, mediates control of epidermal homeostasis by mild cold. Here, we provide additional information explaining why eTRPM8 suppression and TRPM8 stimulation both inhibit keratinocyte growth. We also demonstrate that stimulation of eTRPM8 with icilin may give rise to sustained oscillatory responses. Furthermore, we show that ATP-induced cytosolic and mitochondrial Ca2+ responses are attenuated by eTRPM8 suppression. This suggests positive interplay between eTRPM8 and purinergic signaling pathways, what may serve to facilitate the ER-mitochondria Ca2+ shuttling. Finally, we demonstrate that cold (25°C) induces eTRPM8-dependent superoxide-mediated necrosis of keratinocytes. Altogether, these results are in line with our model of eTRPM8-mediated cold-dependent balance between keratinocyte proliferation and differentiation.

Brown Adipose Tissue Is Linked to a Distinct Thermoregulatory Response to Mild Cold in People.

Brown adipose tissue (BAT) plays an important role in thermoregulation in rodents. Its role in temperature homeostasis in people is less studied. To this end, we recruited 18 men [8 subjects with no/minimal BAT activity (BAT−) and 10 with pronounced BAT activity (BAT+)]. Each volunteer participated in a 6 h, individualized, non-shivering cold exposure protocol. BAT was quantified using positron emission tomography/computed tomography. Body core and skin temperatures were measured using a telemetric pill and wireless thermistors, respectively. Core body temperature decreased during cold exposure in the BAT− group only (−0.34°C, 95% CI: −0.6 to −0.1, p = 0.03), while the cold-induced change in core temperature was significantly different between BAT+ and BAT− subjects (BAT+ vs. BAT−, 0.43°C, 95% CI: 0.20–0.65, p = 0.0014). BAT volume was associated with the cold-induced change in core temperature (p = 0.01) even after adjustment for age and adiposity. Compared to the BAT− group, BAT+ subjects tolerated a lower ambient temperature (BAT−: 20.6 ± 0.3°C vs. BAT+: 19.8 ± 0.3°C, p = 0.035) without shivering. The cold-induced change in core temperature (r = 0.79, p = 0.001) and supraclavicular temperature (r = 0.58, p = 0.014) correlated with BAT volume, suggesting that these non-invasive measures can be potentially used as surrogate markers of BAT when other methods to detect BAT are not available or their use is not warranted. These results demonstrate a physiologically significant role for BAT in thermoregulation in people. This trial has been registered with Clinaltrials.gov: NCT01791114 (https://clinicaltrials.gov/ct2/show/NCT01791114).

Temperature dependence of the control of energy homeostasis requires CART signaling

Cocaine- and amphetamine-regulated transcript (CART) is a key neuropeptide with predominant expression in the hypothalamus central to the regulation of diverse biological processes, including food intake and energy expenditure. While there is considerable information on CART's role in the control of feeding, little is known about its thermoregulatory potential. Here we show the consequences of lack of CART signaling on major parameters of energy homeostasis in CART−/− mice under standard ambient housing (RT, 22°C), which is considered a mild cold exposure for mice, and thermoneutral conditions (TN, 30°C). WT mice kept at RT showed an increase in food intake, energy expenditure, BAT UCP-1 expression, and physical activity compared with TN condition, reflecting the augmented energy demand for thermogenesis at RT. On the molecular level, RT housing led to upregulated mRNA expression of TH, CRH, and TRH at the PVN, while NPY, AgRP and CART mRNA levels in the Arc were downregulated. CART−/− mice displayed elevated adiposity and diminished lean mass across both RT and TN. At RT, CART−/− mice showed unchanged food consumption yet greater body weight gain. In addition, an increase in energy expenditure and heightened BAT thermogenesis marked by UCP-1 protein expression was observed in the CART−/− mice. In contrast, TN-housed CART−/− mice exhibited lower weight gain than WT mice accompanied with pronounced reduction in basal feeding. These findings were correlated with reduced BAT temperature, but unchanged energy expenditure and UCP-1 levels. Interestingly, the respiratory exchange ratio for CART−/− mice, which shifted from lower at RT to higher at TN with respect to WT controls, indicates a transition of relative fuel source preference from fat to carbohydrate in the absence of CART signaling. Taken together, these results demonstrate that CART is a critical regulator of energy expenditure, energy partitioning and utilization dependent on the thermal environment.

Regulation of Adaptive Thermogenesis by the Gut Microbiome

BackgroundAlterations in the gut microbiome contribute to obesity, but the mechanisms by which the gut microbiome regulates energy expenditure and balance are unclear. Adaptive thermogenesis in both humans and mice occurs when changes in ambient temperatures activate thermogenic brown and beige adipose tissue to dissipate energy as heat.AimsThis study was designed to examine the influence of cold ambient temperature on the gut microbiome and to elucidate the contribution of the gut microbiome to adaptive thermogenesis.MethodsC57BL/6 mice were maintained for 3 d at ambient temperatures of 30 °C (thermoneutral), 22 °C (mild cold stress), or 4 °C (severe cold stress). Temperature‐conditioned gut microbiomes were analyzed for predominant gut microbial phyla by qPCR of extracted fecal DNA and were transplanted into commensal‐depleted (antibiotic treated) recipient mice housed at 22 °C. The mice were fed a high fat‐diet, and after 5 w, intraperitoneal glucose tolerance tests were performed. Germ‐free and commensal depleted mice were housed at 30 °C, 22 °C, and 4 °C within a temperature‐controlled comprehensive laboratory animal monitoring system that was custom‐designed to maintain sterile conditions. Indirect calorimetry was performed to determine rates of O2 consumption (VO2) and CO2 production (VCO2). Energy expenditures and respiratory exchange ratios (RER) were calculated using VO2 and VCO2 values. Physical activity was measured according to beam breaks from light sensors within the cages. Core body temperatures were measured using rectal probes. Fecal metabolites were measured by gas chromatography.ResultsHousing mice for 3 d at 4 °C resulted in a dramatic 95% reduction in the abundance of Bacteroidetes and a 62% increase in Firmicutes, the two predominant microbial phyla in the gut. Mice that received a 4 °C‐conditioned microbiome gained less body weight in response to high fat‐feeding and exhibited improved glucose tolerance compared to mice that received the 30 °C‐ or 22 °C‐conditioned microbiomes. Without appreciable changes in core body temperatures, germ‐free and commensal‐depleted mice exhibited reduced energy expenditures at both 30 °C and 4 °C. This occurred despite increased physical activities in germ‐free mice, which were most pronounced at 4 °C. Indicative of preferential utilization of lipids as energy substrates, RER values were reduced in germ free mice at 30 °C and 4 °C, as were fecal contents of short‐chain fatty acids.ConclusionsThe gut microbiome plays a fundamental role in regulating adaptive thermogenesis, potentially by altering intestinal lipid availability or absorption. These effects may be transferred among mice and influence the metabolic response to over‐nutrition. We speculate that impaired thermogenesis in the setting of microbial dysbiosis contributes to the pathogenesis of obesity.Support or Funding InformationBrigham and Women's Hospital, Department of Medicine, Innovation Evergreen Fund and The Harvard Digestive Diseases Center (NIH P30 DK034854).

The enhancement of tolerance to salt and cold stresses by modifying the redox state and salicylic acid content via the cytosolic malate dehydrogenase gene in transgenic apple plants.

SummaryIn this study, we characterized the role of an apple cytosolic malate dehydrogenase gene (MdcyMDH) in the tolerance to salt and cold stresses and investigated its regulation mechanism in stress tolerance. The MdcyMDH transcript was induced by mild cold and salt treatments, and MdcyMDH‐overexpressing apple plants possessed improved cold and salt tolerance compared to wild‐type (WT) plants. A digital gene expression tag profiling analysis revealed that MdcyMDH overexpression largely altered some biological processes, including hormone signal transduction, photosynthesis, citrate cycle and oxidation–reduction. Further experiments verified that MdcyMDH overexpression modified the mitochondrial and chloroplast metabolisms and elevated the level of reducing power, primarily caused by increased ascorbate and glutathione, as well as the increased ratios of ascorbate/dehydroascorbate and glutathione/glutathione disulphide, under normal and especially stress conditions. Concurrently, the transgenic plants produced a high H2O2 content, but a low O2·− production rate was observed compared to the WT plants. On the other hand, the transgenic plants accumulated more free and total salicylic acid (SA) than the WT plants under normal and stress conditions. Taken together, MdcyMDH conferred the transgenic apple plants a higher stress tolerance by producing more reductive redox states and increasing the SA level; MdcyMDH could serve as a target gene to genetically engineer salt‐ and cold‐tolerant trees.

The potential role of irisin in the thermoregulatory responses to mild cold exposure in adults.

To determine the acute effect of a mild cold exposure on thermoregulatory thermogenesis and the role of circulating irisin in the process. We studied 22 adults (9 males, 13 females) aged 57.7 ± 10.07 years and body mass index 27.8 ± 4.52 kg/m(2) . Participants experienced a 90-min exposure to 20°C and 25°C in a randomized cross-over design. Resting metabolic rate (RMR), forearm to finger-tip gradient (FFG), blood pressure (BP), in-the-ear temperature (IET), and fasting bloods were measured on each occasion. There were significant increases in FFG [mean ± SD: +3.8 ± 3.0°C, P < 0.001], systolic blood pressure (SBP) [+8 ± 13 mm Hg, P = 0.015], and diastolic blood pressure (DBP) [+4 ± 6 mm Hg, P = 0.005] and decreases in IET [-0.24 ± 0.29°C, P = 0.001]. Overall, RMR [+190 ± 570 kJ/d, P = 0.135], irisin, glucose or insulin did not differ between temperatures. There were no significant between-gender differences, but males significantly increased SBP (+12 ± 16, P = 0.02) and DBP (+6 ± 7, P = 0.02) with decreases in heart rate (-4 ± 3, P = 0.002), while females did not. Moreover men had approximately 50% higher thermogenic response while women had approximately 25% greater vasoconstrictor response. Adjusted for age, gender, insulin sensitivity, and body composition, fold changes in irisin were inversely related to respiratory quotient (r= -0.54, P = 0.048), while IET was related to FFG (r= -0.55, P = 0.043). Mild cold exposure increased vasoconstriction with a drop in IET and these were related. Greater irisin was related to a greater fasting fat oxidation in the absence of shivering. A potential gender bias in thermoregulation was noted. Am. J. Hum. Biol. 28:699-704, 2016. © 2016 Wiley Periodicals, Inc.

A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis

Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues.

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BackgroundMild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake.ObjectiveTo quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography.MethodsWe exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure.ResultsWe could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure.ConclusionsIt is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.