help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1065
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wijers, S. L. J.
Right arrow Articles by van Marken Lichtenbelt, W. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wijers, S. L. J.
Right arrow Articles by van Marken Lichtenbelt, W. D.
Related Collections
Right arrow Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 11 4299-4305
Copyright © 2007 by The Endocrine Society

Individual Thermogenic Responses to Mild Cold and Overfeeding Are Closely Related

Sander L. J. Wijers, Wim H. M. Saris and Wouter D. van Marken Lichtenbelt

Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Sander Wijers, Department of Human Biology, Maastricht University, P.O. Box 616, NL-6200 MD, Maastricht, The Netherlands. E-mail: S.Wijers{at}hb.unimaas.nl.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Adaptive thermogenesis is defined as the increase in energy expenditure in response to overfeeding or cold. Large interindividual differences in adaptive thermogenesis have been described.

Objective: Because there are indications for a common underlying mechanism, we studied in humans whether the increase in thermogenesis during short-term overfeeding (3 d) is related to mild cold-induced thermogenesis.

Interventions: Thirteen lean male subjects have been exposed to three experimental conditions in respiration chambers: baseline (36 h in energy balance at thermoneutrality, 22 C), overfeeding (84 h at 160% of energy balance, 22 C), and mild cold (84 h in energy balance, 16 C).

Main Outcome Measures: During the interventions, total daily energy expenditure (TDEE), physical activity, skin temperatures, and core temperature were measured. After each condition, fasting plasma norepinephrine concentration was measured.

Results: Overfeeding caused significant increases in TDEE (0.77 MJ/d, P < 0.001). During cold exposure TDEE increased significantly (0.59 MJ/d, P < 0.005), whereas physical activity decreased. The changes in TDEE during both overfeeding and mild cold exposure showed considerable interindividual variation (respectively, –0.11 to 1.61 MJ/d and –0.19 to 1.58 MJ/d). The individual changes in energy expenditure during mild cold exposure and overfeeding were highly correlated (P < 0.005). Fasting norepinephrine plasma concentrations correlated significantly to energy expenditure in both situations (P < 0.05).

Conclusions: These results suggest that both overfeeding-induced and mild cold-induced adaptive thermogenesis share common regulating mechanisms. This indicates that cold exposure could be used as a biomarker for the individual thermogenic response to excess energy intake.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
IN RECENT YEARS, the prevalence of obesity has been increasing in both developed and developing countries (1). Obesity develops when energy intake exceeds energy expenditure. However, after overfeeding, the same amount of excess energy intake does not invoke the same body weight gain in all people. Bouchard et al. (2) showed a range in weight gain of 4.3–13.3 kg after an excess energy intake of 353 MJ in 100 d. This implies large individual differences with a 3-fold range in energy cost of weight gain from 27–82 MJ/kg. These observations were confirmed by others (3, 4).

Because energy intake was standardized in the abovementioned studies, the differences in weight gain have to be caused by a difference in energy expenditure. The most variable parts are activity-induced energy expenditure and diet-induced thermogenesis (DIT). Part of the interindividual differences may be explained by an increase in activity-induced energy expenditure. However, DIT will also be affected. DIT can be divided into two categories: obligatory and facultative DIT. The obligatory part of DIT consists of all processes related to digestion, absorption, and processing of food. The facultative component enables dissipating of energy as heat after a high-calorie meal and prevents the storage of energy. Part of the interindividual differences in weight gain can be explained by the variability in potency of this facultative component (5). After reanalysis of several human studies, Stock (6) showed that considerable interindividual differences exist in facultative thermogenesis.

Similar to excess energy intake, large interindividual differences in energy expenditure have been found when subjects are exposed to mild cold. After a 24-h exposure to 16 C (with a baseline at 22 C), the total daily energy expenditure (TDEE) increases with 0.8 MJ/d; however, the range in interindividual variation was between 0.15 and 1.45 MJ/d (7). Similar results have been found after a decrease in chamber temperature from 28 to 22 C (8).

Adaptive thermogenesis protects the body from cold exposure or regulates energy balance after changes in diet. Possible mechanisms in both humans and small mammals are mitochondrial uncoupling, protein turnover, futile cycling, and nonexercise activity thermogenesis (NEAT) (3, 9). With respect to the regulation, it is clear that the sympathetic nervous system plays an important role in these processes. Animal studies show that blocking of the sympathetic nervous system, which innervates brown adipose tissue and skeletal muscle, impairs temperature regulation during cold exposure and increases storage of calories during normal caloric intake (9). In humans, it is known that both overfeeding and cold exposure lead to an increase in sympathetic activity (10, 11). Moreover, it has been shown that epinephrine infusion in the forearm increased energy expenditure for more than 15% (12). The fact that both overfeeding-induced and cold-induced adaptive thermogenesis are regulated by the sympathetic nervous system gives rise to the assumption that both forms of adaptive thermogenesis share the same mechanisms. Accordingly, we hypothesized that the individual increases in energy expenditure during short-term overfeeding and mild cold exposure are related. For that purpose, the major metabolic routes of energy expenditure were compared between 3 d of overfeeding and 3 d of mild cold exposure in 13 male subjects.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Thirteen healthy male Caucasian volunteers participated in this study. Subject characteristics are shown in Table 1Go. All subjects signed an informed consent for the study protocol, which was approved by the Institutional Review Board of Maastricht University.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Subject characteristics

 
Experimental protocol

Subjects stayed three times in a respiration chamber (13), twice for 36 h and once for 84 h (Fig. 1Go). In both 36-h situations, room temperature was 22 C. During one stay, subjects were fed in energy balance (baseline), and during the other stay, they received a high-energy diet during the stay and 48 h before entering the chamber (overfeeding). In the 84-h situation, the room temperature was 16 C and subjects were fed in energy balance (mild cold). After the baseline situation, subjects were randomly assigned to both other situations. The temperature of the mild cold situation (16 C) in this study setting had been validated earlier (14). No shivering occurred in that previous study (14), as was verified with electromyography. Nevertheless, in the present study, each participant had to fill out an hourly questionnaire about whether shivering occurred. Energy balance was based on individually calculated energy requirements; after measurement of sleeping metabolic rate (SMR) during the first night in the respiration chamber, an estimated TDEE was calculated by multiplying SMR with a physical activity index (PAI) of 1.6 (15). Energy intake was adjusted accordingly.


Figure 1
View larger version (17K):
[in this window]
[in a new window]

  		FIG. 1. The experimental procedure followed by each subject. Each subject followed all three situations, starting with the baseline measurement. Baseline and overfeeding measurements comprised 36 h in the respiration chamber, mild cold measurements 84 h. After each stay, blood samples were taken.

 
During overfeeding, subjects received a diet containing 160% of the energy required for energy balance 2 d before and during their stay in the respiration chamber. The PAI of the free-living situation was estimated after questioning the subject; for each hour of moderate physical activity per day, the PAI was increased with 0.2 above the standard 1.6 for sedentary subjects. The SMR of the previous respiration chamber stay was used as a base for this calculation.

Macronutrient composition of all meals was 47, 38, and 15% energy from carbohydrate, fat, and protein, respectively.

Subjects entered the respiration chamber at 2000 h. The first night they could become accustomed to to the situation. Clothing was standardized. A standard daily activity protocol was applied (16), which described all activities required by the subjects. The subjects measured their own body weight each morning in fasted state after voiding on a digital balance, accurate to the nearest 0.1 kg.

Immediately upon leaving the respiration chamber, blood samples were drawn from an iv catheter that was inserted 30 min earlier. The interval between two stays in the chamber was at least 2 wk.

Energy expenditure

The respiration chamber is a 14-m3 room, furnished with a bed, chair, television, radio, telephone, computer, washbowl, and deep-freeze toilet. Air locks provide passage for exchange of food and urine. Energy expenditure was determined from the subjects’ O2 consumption, CO2 production, and urine nitrogen excretion according to the Weir equation (17). The respiration chamber was ventilated with fresh air at a rate of 70–80 liters/min. A dry gas meter (G4; Schlumberger, Dordrecht The Netherlands) measured the ventilation rate. A paramagnetic O2 analyzer (OA 184A; Servomex, Crowborough, UK) and an infrared CO2 analyzer (Uras 3G; Hartmann & Braun, Frankfurt am Main, Germany) were used to analyze the samples of the in- and outgoing air. Ingoing air was analyzed once every 15 min and outgoing air every 5 min. Relative humidity was kept between 53 and 55%. Physical activity was monitored by means of a radar system, based on the Doppler principle (13). Twenty-four-hour urine samples were collected in containers with 10 ml H2SO4 to prevent nitrogen loss by evaporation. Total daily nitrogen excretion was calculated with 24-h urine nitrogen concentration, which was measured with a nitrogen analyzer (CHN-O-Rapid; Heraeus, Hanau, Germany).

TDEE was calculated over 24-h intervals from 0800–0800 h. SMR is defined to be the lowest energy expenditure at night (measured over three consecutive hours). Both TDEE and SMR have been corrected for fat-free mass (FFM) through linear regression, because 80% of interindividual differences in energy expenditure can be explained by FFM (18). The residuals of the regression between energy expenditure and FFM have been added to the average energy expenditure.

Body temperature

Skin temperatures were measured continuously during the experiments by means of iButtons (type DS1921H; Maxim/Dallas Semiconductor Corp., Dallas, TX), which have recently been validated for studies in humans (20). Temperature sensors were attached to the skin using fixomull tape (BSN, Hamburg, Germany) at the 15 positions of the adapted Mitchell/Wyndham equation for mean skin temperature (21). The averages of temperatures of the face, chest, abdomen, scapula, subscapula, and lower back were regarded as proximal temperatures. Averages of hand and foot temperatures were regarded as distal temperatures. Core temperatures were measured the last 24 h of each respiration chamber stay using a telemetric pill (CorTemp; HQInc, Palmetto, FL) that measures temperature in the intestine and transmits data to a mobile receiver. The silicon-coated pill was ingested with breakfast.

Body composition

Whole-body density was determined in the fasted state by hydrodensitometry with simultaneous assessment of the lung volume using the helium dilution technique. Body weight was measured using a digital balance with an accuracy of 0.001 kg (ID1 plus; Mettler Toledo, Tiel, The Netherlands). Under water, body weight was measured using a digital balance with an accuracy of 0.01 kg (E1200; Sauter, Ebingen,Germany). Lung volume was measured by use of a spirometer (Volugraph 2000; Mijnhardt, Bunnik, The Netherlands). Percent body fat was calculated using the equation of Siri (22).

Blood analyses

Blood samples in the fasted state were taken to assess catecholamine, insulin, leptin, free fatty acids (FFA), adiponectin, and active ghrelin levels. Catecholamine blood samples were taken in lithium-heparin-containing tubes. Other samples were taken in EDTA-containing tubes to prevent clotting. Plasma was obtained by centrifugation, frozen in liquid nitrogen, and stored at –80 C until further analysis. Before centrifugation, glutathione was added to the catecholamine samples and phenylmethylsulfonyl fluoride was added to the active ghrelin samples. Plasma insulin, leptin, FFA, active ghrelin, and adiponectin levels were determined using RIA (Linco Research, St. Charles, MO). Catecholamine levels were assessed by HPLC according to the method of Alberts et al. (23).

Statistics

Comparisons were made using ANOVA repeated measures, with simple contrast for individual comparisons between groups. Linear regression analyses were made to identify correlations between cold- and overfeeding-induced changes and between variables. Cook’s distances larger than 0.5 and studentized deleted residuals larger than 4.0 were considered to be outliers. Statistical analyses were performed using SPSS 11.0 for Mac. Values were considered to be statistically significant if P < 0.05.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Energy expenditure

TDEE (corrected for FFM) increased significantly during both overfeeding (P < 0.001) and mild cold exposure (P < 0.005) (Table 2Go). Overfeeding caused an average increase of 0.76 MJ/d (6.6% of TDEE), with a range of –0.11 to 1.61 MJ/d (0–14%). During mild cold exposure, an increase of 0.59 MJ/d (5.1% of TDEE) occurred, with a range of –0.19 to 1.58 MJ/d (0–14%). The increase in TDEE during overfeeding was significantly related to the increase in TDEE during mild cold exposure (r = 0.63; P < 0.05) (dotted line, Fig. 2AGo). After deleting an outlier (subject 11, Cook’s distance 0.75) the regression improved substantially (r = 0.75; P < 0.005) (solid line, Fig. 2AGo). SMR (corrected for FFM) increased significantly during overfeeding only (P < 0.005), not during mild cold exposure (Table 2Go). The change in SMR during overfeeding correlated significantly to the change during mild cold exposure (r = 0.69; P < 0.01) (Fig. 2BGo). Respiratory quotient (RQ) and urine nitrogen production increased significantly during overfeeding (both P < 0.001). Activity counts decreased significantly during cold exposure (P < 0.001).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Summarized respiration chamber data

 

Figure 2
View larger version (13K):
[in this window]
[in a new window]

  		FIG. 2. Energy expenditure: overfeeding vs. mild cold exposure. The relations between the change in TDEE (A) and SMR (B) corrected for FFM during overfeeding and during mild cold exposure. The correlation coefficient of this relation for TDEE was 0.63 (P < 0.05). One outlier (Cook’s distance 0.75) existed; reviewing questionnaire data revealed that the subject was more stressed in the mild cold situation than in both the baseline and the overfeeding situation. Stress could increase energy expenditure, and therefore this subject was excluded from this analysis. The correlation coefficient after removing was 0.75 (P < 0.005). The correlation coefficient of this relation for SMR was 0.69 (P < 0.01). No outliers existed.

 
Body temperature

During overfeeding, core temperature, skin temperature, proximal skin temperature, and distal skin temperature increased (P < 0.05) (Table 3Go). During mild cold exposure, core temperature was not significantly different, but skin temperature, proximal skin temperature, and distal skin temperature decreased significantly (P < 0.001) (Table 3Go). The gradients core-proximal and proximal-distal temperature, measures for core insulation, increased significantly during mild cold exposure (both P < 0.001) (Table 3Go). Changes in core and skin temperatures during overfeeding and mild cold exposure did not correlate. Energy expenditure did not correlate significantly with core temperature, skin temperatures, or temperature gradients.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Summarized temperature data

 
Blood analyses

Fasting insulin, norepinephrine, epinephrine, active ghrelin, and adiponectin concentration did not change after overfeeding. However, the overfeeding experiment did result in a significant decrease in fasting FFA concentration (P < 0.005) and an increase in leptin concentration (P < 0.05) (Table 4Go). After mild cold exposure, only fasting norepinephrine concentration increased significantly (P < 0.001). No significant changes in the plasma concentration of fasting insulin, epinephrine, FFA, leptin, active ghrelin, and adiponectin occurred (Table 4Go). Changes in fasting insulin, norepinephrine, FFA, active ghrelin, and adiponectin concentrations after overfeeding correlated with the changes after mild cold exposure [respectively, r = 0.84, P < 0.001; r = 0.87, P < 0.002 (with outlier correction); r = 0.92, P < 0.001 (with correction for Cook’s distance); r = 0.78, P < 0.05; and r = 0.57, P = 0.051]. Changes in leptin plasma concentration after overfeeding and mild cold exposure did not correlate. Leptin concentrations correlated with body fat (r = 0.83, P < 0.002; r = 0.84, P < 0.001; and r = 0.92, P < 0.001 for baseline, overfeeding, and mild cold exposure, respectively). Remarkably, the change in leptin concentration after overfeeding correlated also to body fat (r = 0.77, P < 0.005). Differences in energy expenditure correlated significantly to differences in fasting plasma norepinephrine level after both overfeeding (r = 0.56, P < 0.05) and mild cold exposure (r = 0.72, P < 0.02) (Fig. 3Go), although no significant change in norepinephrine after overfeeding exists.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Summarized blood sample data

 

Figure 3
View larger version (12K):
[in this window]
[in a new window]

  		FIG. 3. TDEE vs. norepinephrine concentrations. The relation between the change in TDEE corrected for FFM and fasting plasma norepinephrine concentration during both overfeeding (r = 0.56, P < 0.05) (A) and mild cold exposure (r = 0.72, P < 0.02) (B).

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
We hypothesized that the individual responses in energy expenditure during mild cold exposure and during short-time overfeeding are related. The results showed that there are indeed significant relations.

Overfeeding caused an increase in energy expenditure of 0.71 MJ/d, which is 6.7% of the TDEE. The range is large, –0.11 to 1.61 MJ/d (0–14%). Some subjects dissipated none of the extra energy ingested, whereas others dissipated up to 23% of this excess. This difference can lead to a considerable variation in weight gain after overfeeding and might therefore be a factor in the development of obesity. The large variation in weight gain has been shown by several groups (2, 3, 4). Our results show similar interindividual differences in energy expenditure.

Mild cold exposure caused an increase in energy expenditure of 0.59 MJ/d (5.1% of TDEE) with a similar range of –0.19 to 1.58 MJ/d (0–14%). This is consistent to earlier studies (7, 8) and comparable to the change in energy expenditure after overfeeding. It is for the first time demonstrated that the individual responses to overfeeding and cold exposure are so closely related to each other.

The mechanism behind these increases in energy expenditure are often attributed to an increase of physical activity or to NEAT (3, 24). However, the radar activity counts decreased during overfeeding and mild cold exposure. Therefore, it is unlikely that NEAT contributed to the increases in energy expenditure.

SMR was not changed during mild cold exposure, because subjects could create their own microclimate under the duvet at night. However, SMR change during mild cold exposure correlated to the change during overfeeding. This can be explained by a prolonged action of the increase in energy expenditure during mild cold exposure in the metabolic responders during night. Another possibility is a metabolic reaction due to the low face temperature, which can act as a cold sensor (25). SMR was increased during overfeeding, indicating that the DIT lasted for many hours after the last meal. This has been observed before (4, 26). Consequently, it is likely that we did not measure a SMR, but SMR plus a part of the DIT.

The increased RQ and nitrogen production and the decrease of fasted plasma FFA concentration in the overfeeding situation can be explained by a quantitatively larger amount of proteins and carbohydrates in the diet consumed relative to fat (27). The amount of fat not expended is most probably stored in the adipose tissue and to a lesser extent in muscle.

In line with the increase in energy expenditure, the increases of skin temperatures relative to baseline during overfeeding indicate extra dissipation of heat to the environment. To our knowledge, no other overfeeding studies registered skin temperatures. An increase in skin temperature has been shown directly after a large meal (28). The elevation in core temperature shows up in the results of Rising et al. (29), who showed that after starvation, core temperature dropped and increased again after refeeding. During cold exposure, however, skin temperature decreased, with a concomitant rise in energy expenditure. This is caused by the large heat loss to the environment, which cannot be measured using temperature probes only. Because temperature gradients between environment and body were different for overfeeding and mild cold exposure, no correlations could be found between the differences in skin and core temperature. To assess these relations, heat flux measurements are needed.

Leptin is widely recognized as a regulator of adipose tissue mass. A high level of leptin is associated with a large adipose tissue mass and signals for positive energy balance. A low level of leptin works the other way around (30). Our study confirms that leptin concentration is correlated to fat mass. Indeed, in obese subjects, leptin levels are elevated. However, in obese subjects, energy balance is often not changed due to an increased insensitivity to leptin (30).

Although leptin is generally accepted to be a long-term regulator of energy balance, less well known is our observation that plasma leptin concentration increased after short-term overfeeding. This indicates a fast response of leptin upon activation of adipose tissue to prevent excess energy storage (31). Moreover, our study shows that the increase in leptin concentration is also related to body fat. This can be explained by the larger secreting tissue (i.e. the adipose tissue).

Overfeeding and mild cold exposure shared 57% of their interindividual variation in total daily energy expenditure. This indicates that both cold- and overfeeding-induced adaptive thermogenesis share the same regulation. This common origin has previously been shown in several studies in mice, as reviewed by Lowell and Spiegelman (9). It has been shown that the sympathetic nervous system regulates adaptive thermogenesis in animals (32, 33). Also in humans, sympathetic stimulation of skeletal muscle results in an increase in energy expenditure (12). Therefore, it is likely that interindividual differences in sensitivity or activity of the sympathetic nervous system are responsible for the large interindividual differences in adaptive thermogenesis. The correlations of changes in fasting norepinephrine plasma levels with changes in TDEE after both overfeeding and mild cold exposure indicate that a larger secretion of norepinephrine causes increases in energy expenditure. Correlations of the changes of fasting plasma insulin, adiponectin, active ghrelin, and FFA after overfeeding and mild cold exposure underline the role of the sympathetic nervous system in adaptive thermogenesis. Several recent studies indicate the central role of the sympathetic nervous system in the regulation of these parameters. First, epinephrine is able to inhibit pancreatic insulin secretion (34); hence, fasting plasma insulin levels might be decreased in sympathetic responders. Second, blocking the sympathetic nervous system increases adiponectin plasma levels (35). Third, electrical stimulation of the sympathetic nervous system invoked an increase in ghrelin concentration in rats (36). Fourth, administration of ß-adrenergic agonists stimulate lipolysis, which increases FFA concentrations (37, 38). Therefore, there are strong indications that the sympathetic nervous system is the main regulator of adaptive thermogenesis.

In small mammals, brown adipose tissue serves as a thermogenic organ, which uncouples mitochondrial respiration using an uncoupling protein (UCP)-1. UCP-1 activity is regulated by the ß-cells of the sympathetic nervous system. The relevance of brown adipose tissue is believed to be marginal in most adult humans (39), although recent data indicate cold-induced activity of brown adipose tissue in adults (40). Another potential mechanism in humans is uncoupling by UCP-3, a UCP-1 homolog that is present in skeletal muscle tissue. However, it has been shown that the UCP-3 protein content and mRNA expression have not been increased after mild cold exposure (41). On the other hand, FFA are known to stimulate UCP-3 activity (42). High metabolic responders show a less decreased FFA concentration than low responders after overfeeding. After mild cold exposure, high metabolic responders even show an increase in FFA concentration. This (relative) increase in FFA concentration in high responders might cause an increased mitochondrial uncoupling in skeletal muscle compared with low responders, possibly through UCP-3.

The relation in the metabolic reaction to overfeeding and mild cold exposure is not only helpful in the identification of the underlying mechanisms. Mild cold exposure per se might also work as a prevention method or cure for obesity, because it is easy to decrease home temperature slightly (19). However, it is not entirely possible to translate our results directly to other groups such as obese subjects or women, because of possible different metabolic responses. Therefore, these groups will be studied in the near future.

We initiated this study to see whether cold exposure could be used as a proxy functional test for the individual thermogenic capacity in a situation of excess energy intake. Overfeeding is a complex and tedious type of functional test and not very appreciated by subjects, in particular obese subjects. The results do show an excellent correlation and could lead to a simpler functional test for thermogenic capacity.


   Acknowledgments
 
We thank Paul Schoffelen and Loek Wouters for their technical assistance with indirect calorimetry and Wendy Sluijsmans and Jos Stegen for the plasma and urine sample analyses.


   Footnotes
 
Disclosure Statement: All authors have nothing to declare.

First Published Online September 4, 2007

Abbreviations: DIT, Diet-induced thermogenesis; FFA, free fatty acids; FFM, fat-free mass; NEAT, nonexercise activity thermogenesis; PAI, physical activity index; RQ, respiratory quotient; SMR, sleeping metabolic rate; TDEE, total daily energy expenditure; UCP, uncoupling protein.

Received May 14, 2007.

Accepted August 24, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. World Health Organization 2000 Obesity: preventing and managing the global epidemic. Report of a WHO consultation. Geneva: World Health Organization
  2. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Theriault G, Dussault J, Moorjani S, Pinault S, Fournier G 1990 The response to long-term overfeeding in identical twins. N Engl J Med 322:1477–1482[Abstract]
  3. Levine JA, Eberhardt NL, Jensen MD 1999 Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 283:212–214[Abstract/Free Full Text]
  4. Joosen AM, Bakker AH, Westerterp KR 2005 Metabolic efficiency and energy expenditure during short-term overfeeding. Physiol Behav 85:593–597[CrossRef][Medline]
  5. Himms-Hagen J 1989 Role of thermogenesis in the regulation of energy balance in relation to obesity. Can J Physiol Pharmacol 67:394–401[Medline]
  6. Stock MJ 1999 Gluttony and thermogenesis revisited. Int J Obes Relat Metab Disord 23:1105–1117[CrossRef][Medline]
  7. van Marken Lichtenbelt WD, Schrauwen P, van De Kerckhove S, Westerterp-Plantenga MS 2002 Individual variation in body temperature and energy expenditure in response to mild cold. Am J Physiol Endocrinol Metab 282:E1077–E1083
  8. Warwick PM, Busby R 1990 Influence of mild cold on 24 h energy expenditure in ‘normally’ clothed adults. Br J Nutr 63:481–488[CrossRef][Medline]
  9. Lowell BB, Spiegelman BM 2000 Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–660[Medline]
  10. Landsberg L 2006 Feast or famine: the sympathetic nervous system response to nutrient intake. Cell Mol Neurobiol 26:495–506[CrossRef]
  11. Leppaluoto J, Paakkonen T, Korhonen I, Hassi J 2005 Pituitary and autonomic responses to cold exposures in man. Acta Physiol Scand 184:255–264[CrossRef][Medline]
  12. Simonsen L, Bulow J, Madsen J, Christensen NJ 1992 Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue. Am J Physiol 263:E850–E855
  13. Schoffelen PF, Westerterp KR, Saris WH, Ten Hoor F 1997 A dual-respiration chamber system with automated calibration. J Appl Physiol 83:2064–2072[Abstract/Free Full Text]
  14. van Ooijen AM, van Marken Lichtenbelt WD, van Steenhoven AA, Westerterp KR 2004 Seasonal changes in metabolic and temperature responses to cold air in humans. Physiol Behav 82:545–553[CrossRef][Medline]
  15. Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR 1997 Energy balance in a respiration chamber: individual adjustment of energy intake to energy expenditure. Int J Obes Relat Metab Disord 21:769–774[CrossRef][Medline]
  16. Westerterp-Plantenga MS, van Marken Lichtenbelt WD, Strobbe H, Schrauwen P 2002 Energy metabolism in humans at a lowered ambient temperature. Eur J Clin Nutr 56:288–296[CrossRef][Medline]
  17. Weir JB 1949 New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109:1–9[Free Full Text]
  18. Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C 1986 Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. J Clin Invest 78:1568–1578[Medline]
  19. Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM, Ruden D, Pietrobelli A, Barger JL, Fontaine KR, Wang C, Aronne LJ, Wright SM, Baskin M, Dhurandhar NV, Lijoi MC, Grilo CM, DeLuca M, Westfall AO, Allison DB 2006 Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond) 30:1585–1594[CrossRef][Medline]
  20. van Marken Lichtenbelt WD, Daanen HA, Wouters L, Fronczek R, Raymann RJ, Severens NM, Van Someren EJ 2006 Evaluation of wireless determination of skin temperature using iButtons. Physiol Behav 88:489–497[CrossRef][Medline]
  21. Choi JK, Miki K, Sagawa S, Shiraki K 1997 Evaluation of mean skin temperature formulas by infrared thermography. Int J Biometeorol 41:68–75[CrossRef][Medline]
  22. Siri WE 1961 Body composition from fluid spaces and density: analysis of methods. In: Bozek J, Henschel A, eds. Techniques for measuring body composition. Washington, DC: National Academy of Sciences; 223–224
  23. Alberts G, Boomsma F, Man in ’t Veld AJ, Schalekamp MA 1992 Simultaneous determination of catecholamines and dobutamine in human plasma and urine by high-performance liquid chromatography with fluorimetric detection. J Chromatogr 583:236–240[Medline]
  24. Thompson WG, Cook DA, Clark MM, Bardia A, Levine JA 2007 Treatment of obesity. Mayo Clin Proc 82:93–101; quiz 101–102[Abstract/Free Full Text]
  25. Mundel T, Bunn SJ, Hooper PL, Jones DA 2007 The effects of face cooling during hyperthermic exercise in man: evidence for an integrated thermal, neuroendocrine and behavioural response. Exp Physiol 92:187–195[Abstract/Free Full Text]
  26. Goldberg GR, Prentice AM, Davies HL, Murgatroyd PR 1988 Overnight and basal metabolic rates in men and women. Eur J Clin Nutr 42:137–144[Medline]
  27. Jebb SA, Prentice AM, Goldberg GR, Murgatroyd PR, Black AE, Coward WA 1996 Changes in macronutrient balance during over- and underfeeding assessed by 12-d continuous whole-body calorimetry. Am J Clin Nutr 64:259–266[Abstract/Free Full Text]
  28. Westerterp-Plantenga MS, Wouters L, ten Hoor F 1990 Deceleration in cumulative food intake curves, changes in body temperature and diet-induced thermogenesis. Physiol Behav 48:831–836[CrossRef][Medline]
  29. Rising R, Keys A, Ravussin E, Bogardus C 1992 Concomitant interindividual variation in body temperature and metabolic rate. Am J Physiol 263:E730–E734
  30. Friedman JM, Halaas JL 1998 Leptin and the regulation of body weight in mammals. Nature 395:763–770[CrossRef][Medline]
  31. Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF 1996 Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab 81:4162–4165[Abstract/Free Full Text]
  32. Thomas SA, Palmiter RD 1997 Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387:94–97[CrossRef][Medline]
  33. Landsberg L, Saville ME, Young JB 1984 Sympathoadrenal system and regulation of thermogenesis. Am J Physiol 247:E181–E189
  34. Nonogaki K 2000 New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia 43:533–549[CrossRef][Medline]
  35. Nowak L, Adamczak M, Wiecek A 2005 Blockade of sympathetic nervous system activity by rilmenidine increases plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 18:1470–1475[CrossRef][Medline]
  36. Mundinger TO, Cummings DE, Taborsky Jr GJ 2006 Direct Stimulation of ghrelin secretion by sympathetic nerves. Endocrinology 147:2893–2901[Abstract/Free Full Text]
  37. Hoeks J, van Baak MA, Hesselink MK, Hul GB, Vidal H, Saris WH, Schrauwen P 2003 Effect of ß1- and ß2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans. Am J Physiol Endocrinol Metab 285:E775–E782
  38. Schiffelers SLH, Saris WHM, Boomsma F, van Baak MA 2001 ß1- and ß2-adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 86:2191–2199[Abstract/Free Full Text]
  39. Himms-Hagen J 2001 Does brown adipose tissue (BAT) have a role in the physiology or treatment of human obesity? Rev Endocr Metab Disord 2:395–401[CrossRef][Medline]
  40. Nedergaard J, Bengtsson T, Cannon B 2007 Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 293:E444–E452
  41. Schrauwen P, Westerterp-Plantenga MS, Kornips E, Schaart G, van Marken Lichtenbelt WD 2002 The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans. Int J Obes Relat Metab Disord 26:450–457[CrossRef][Medline]
  42. Schrauwen P, Hoeks J, Schaart G, Kornips E, Binas B, Van De Vusse GJ, Van Bilsen M, Luiken JJ, Coort SL, Glatz JF, Saris WH, Hesselink MK 2003 Uncoupling protein 3 as a mitochondrial fatty acid anion exporter. FASEB J 17:2272–2274[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 NEJMHome page
W. D. van Marken Lichtenbelt, J. W. Vanhommerig, N. M. Smulders, J. M.A.F.L. Drossaerts, G. J. Kemerink, N. D. Bouvy, P. Schrauwen, and G.J. J. Teule
Cold-Activated Brown Adipose Tissue in Healthy Men
N. Engl. J. Med., April 9, 2009; 360(15): 1500 - 1508.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wijers, S. L. J.
Right arrow Articles by van Marken Lichtenbelt, W. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wijers, S. L. J.
Right arrow Articles by van Marken Lichtenbelt, W. D.
Related Collections
Right arrow Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals