Why body heat production - which is akin to exercise it seems to me - would be different is a mystery.
While I'm a big proponent of exercise, burning calories in exercise is far from equivalent to the way the body expends calories to regulate temperature, affording plenty of opportunities for the impact of the two activities on health and longevity to diverge. Yes, exercise (and other voluntary physical activities) does generate heat and can help maintain body temperature, but it is just one of many ways of accomplishing that end, as illustrated in this amusing graphic:
Uncoupling proteins, either UCP1 in brown adipose tissue (aka BAT or 'brown fat'), or UCP3 in muscle tissue (to a lesser extent - see below), are a major mechanism by which the body generates heat for thermoregulation. Proton leakage across the mitochondrial membrane, mostly controlled by these UCPs, accounts for 20-30% of the resting metabolic rate in rats  - so they have a big effect!
And an increase in this way of expending energy has been found to reduce reactive oxygen species (ROS) generation in and around the mitochondria, which could be one way to explain how cold exposure, which raises uncoupling protein levels, benefits health and longevity. Here is a graphic (from ) of the many ways that upregulating UCPs can benefit health:
It was once thought that adult humans had little brown fat, and therefore little UCP1, and that there was nothing that could be done to change that. But recently it was discovered that not only do we have BAT, but the level of brown fat in the human body can be increased via cold exposure. You've just gotta love the name of this study - it's called the "Impact of Chronic Cold Exposure in Humans (ICEMAN)" study . In it, researchers found that having men sleep in a cool room (66F) for a month increased brown fat levels and activity by 42% relative to thermal neutral sleeping, as well as improved insulin sensitivity and glucose metabolism. In contrast, sleeping in a warm (81F) room decreased the level of brown fat and its metabolic activity by about 20% in the men.
So like in rodents, it appears brown fat and UCP1 can be increased in humans via cold exposure, which is likely to be a good thing based on the rodent longevity data discussed in previous posts, not to mention the finding from  of improved insulin sensitivity.
But what about UCP3, which we have much more of than UCP1 and which is the homolog of UCP1 but which occurs in skeletal muscles rather than (or in addition to) brown fat? What does UCP3 do and what influences UCP3 expression?
Unlike UCP1, it is not clear that UCP3 contributes significantly to thermal regulation , despite the fact that it can indeed uncouple the ATP synthesis process in mitochondria just like UCP1, and hence contribute to heat generation. Its true role doesn't appear to be very clear, according to review article , but it definitely seems to reduce ROS generation in the mitochondria of skeletal muscles, and thereby protect mitochondria from oxidative damage, which is a very good thing. Other known or suspected benefits of UCP3 upregulation are shown in the diagram above.
So what can be done to upregulate UCP3 levels in muscles?
Cold exposure appears to only modestly (if at all ) and perhaps only temporarily increase the level of UPC3 in muscles , more as a result of increased energy expenditure than via a direct increase in expression of mRNA for UCP3, which strangely was actually downregulated by cold. What appears to be happening is that cold exposure , exercise , fasting , and particularly the combination, i.e. exercising in the fasting state , increases the level of free fatty acids in muscle cells (FFAs are used by muscles as fuel when glucose isn't available), and it is these FFAs that facilitate the expression of of UCP3 mRNA, and subsequently increase UCP3 levels in muscle cells.
TL;DR - Cold exposure, fasting, exercise, and especially exercise in the fasted state can upregulate the two major uncoupling proteins, UCP1 and UCP3. These proteins appear to enable the body to burn calories more "cleanly", reducing oxidative damage and increasing insulin sensitivity. Upregulation of these proteins are likely just one of several pathways by which cold exposure, fasting and exercise have beneficial effects on health and longevity.
 Diabetes. 2014 Nov;63(11):3686-98. doi: 10.2337/db14-0513. Epub 2014 Jun 22.
Temperature-acclimated brown adipose tissue modulates insulin sensitivity in
Lee P(1), Smith S(1), Linderman J(1), Courville AB(2), Brychta RJ(1), Dieckmann
W(3), Werner CD(1), Chen KY(1), Celi FS(4).
In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced
thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it
impacts on energy metabolism have not been investigated in humans. We examined
the effects of temperature acclimation on BAT, energy balance, and substrate
metabolism in a prospective crossover study of 4-month duration, consisting of
four consecutive blocks of 1-month overnight temperature acclimation (24 °C
[month 1] → 19 °C [month 2] → 24 °C [month 3] → 27 °C [month 4]) of five healthy
men in a temperature-controlled research facility. Sequential monthly acclimation
modulated BAT reversibly, boosting and suppressing its abundance and activity in
mild cold and warm conditions (P < 0.05), respectively, independent of seasonal
fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by
DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05),
evident only after cold acclimation. Circulating and adipose tissue, but not
skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal
changes concordant with cold-acclimated insulin sensitization. These results
suggest regulatory links between BAT thermal plasticity and glucose metabolism in
humans, opening avenues to harnessing BAT for metabolic benefits.
© 2014 by the American Diabetes Association. Readers may use this article as long
as the work is properly cited, the use is educational and not for profit, and the
work is not altered.
 Front Physiol. 2015 Feb 10;6:36. doi: 10.3389/fphys.2015.00036. eCollection 2015.
Mitochondrial uncoupling proteins and energy metabolism.
Busiello RA(1), Savarese S(2), Lombardi A(3).
(1)Dipartimento di Scienze e Tecnologie, Università degli Studi del Sannio
Benevento, Italy. (2)Dipartimento di Scienze e Tecnologie Ambientali, Biologiche
e Farmaceutiche, Seconda Università degli Studi di Napoli Caserta, Italy.
(3)Dipartimento di Biologia, Università degli Studi di Napoli Napoli, Italy.
Understanding the metabolic factors that contribute to energy metabolism (EM) is
critical for the development of new treatments for obesity and related diseases.
Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP
synthesis, and the process of proton-leak plays a crucial role. Proton-leak
accounts for a significant part of the resting metabolic rate (RMR) and therefore
enhancement of this process represents a potential target for obesity treatment.
Since their discovery, uncoupling proteins have stimulated great interest due to
their involvement in mitochondrial-inducible proton-leak. Despite the widely
accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1), which
was the first in this family to be discovered, the reactions catalyzed by its
homolog UCP3 and the physiological role remain under debate. This review provides
an overview of the role played by UCP1 and UCP3 in mitochondrial
uncoupling/functionality as well as EM and suggests that they are a potential
therapeutic target for treating obesity and its related diseases such as type II
 Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E11-7.
Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated
Schrauwen P(1), Hesselink MK, Vaartjes I, Kornips E, Saris WH, Giacobino JP,
(1)Department of Human Biology, Maastricht University, 6200 MD Maastricht, The
Human and rodent uncoupling protein (UCP)3 mRNA is upregulated after acute
exercise. Moreover, exercise increases plasma levels of free fatty acid (FFA),
which are also known to upregulate UCP3. We investigated whether the upregulation
of UCP3 after exercise is an effect of exercise per se or an effect of FFA levels
or substrate oxidation. Seven healthy untrained men [age: 22.7 +/- 0.6 yr; body
mass index: 23.8 +/- 1.0 kg/m(2); maximal O2 uptake (VO2 max): 3,852 +/- 211
ml/min] exercised at 50% VO2 max for 2 h and then rested for 4 h. Muscle biopsies
and blood samples were taken before and immediately after 2 h of exercise and 1
and 4 h in the postexercise period. To modulate plasma FFA levels and fat/glucose
oxidation, the experiment was performed two times, one time with glucose
ingestion and one time while fasting. UCP3 mRNA and UCP3 protein were determined
by RT-competitive PCR and Western blot. In the fasted state, plasma FFA levels
significantly increased (P < 0.0001) during exercise (293 +/- 25 vs. 1,050 +/-
127 micromol/l), whereas they were unchanged after glucose ingestion (335 +/- 54
vs. 392 +/- 74 micromol/l). Also, fat oxidation was higher after fasting (P <
0.05), whereas glucose oxidation was higher after glucose ingestion (P < 0.05).
In the fasted state, UCP3L mRNA expression was increased significantly (P < 0.05)
4 h after exercise (4.6 +/- 1.2 vs. 9.6 +/- 3.3 amol/microg RNA). This increase
in UCP3L mRNA expression was prevented by glucose ingestion. Acute exercise had
no effect on UCP3 protein levels. In conclusion, we found that acute exercise had
no direct effect on UCP3 mRNA expression. Abolishing the commonly observed
increase in plasma FFA levels and/or fatty acid oxidation during and after
exercise prevents the upregulation of UCP3 after acute exercise. Therefore, the
previously observed increase in UCP3 expression appears to be an effect of
prolonged elevation of plasma FFA levels and/or increased fatty acid oxidation.
 International Journal of Obesity (2002) 26, 450-457. DOI: 10.1038/sj/ijo/0801943
The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans
OBJECTIVE: In rodents, adaptive thermogenesis in response to cold exposure and high-fat feeding is accomplished by the activation of the brown adipose tissue specific mitochondrial uncoupling protein, UCP1. The recently discovered human uncoupling protein 3 is a possible candidate for adaptive thermogenesis in humans. In the present study we examined the effect of mild cold exposure on the mRNA and protein expression of UCP3.
SUBJECTS: Ten healthy male volunteers (age 24.4±1.6 y; height 1.83±0.02 m; weight 77.3±3.0 kg; percentage body fat 19±2)
DESIGN: Subjects stayed twice in the respiration chamber for 60 h (20.00-8.00 h); once at 22°C (72°F), and once at 16°C (61°F). After leaving the respiration chamber, muscle biopsies were taken and RT-competitive-PCR and Western blotting was used to measure UCP3 mRNA and protein expression respectively.
RESULTS: Twenty-four-hour energy expenditure was significantly increased at 16°C compared to 22°C (P<0.05). At 16°C, UCP3T (4.6±1.0 vs 7.7±1.5 amol/µg RNA, P=0.07), UCP3L (2.0±0.5 vs 3.5±0.9 amol/µg RNA, P=0.1) and UCP3S (2.6±0.6 vs 4.2±0.7 amol/µg RNA, P=0.07) mRNA expression tended to be lower compared with at 22°C, whereas UCP3 protein content was, on average, not different. However, the individual differences in UCP3 protein content (16-22°C) correlated positively with the differences in 24 h energy expenditure (r=0.86, P<0.05).
CONCLUSION: The present study suggests that UCP3 protein content is related to energy metabolism in humans and might help in the metabolic adaptation to cold exposure. However, the down-regulation of UCP3 mRNA with mild cold exposure suggests that prolonged cold exposure will lead to lower UCP3 protein content. What the function of such down-regulation of UCP3 could be is presently unknown.
 Int J Sports Med. 2012 Feb;33(2):94-100. doi: 10.1055/s-0031-1287799. Epub 2011
Human mRNA response to exercise and temperature.
Slivka DR(1), Dumke CL, Tucker TJ, Cuddy JS, Ruby B.
(1)University of Nebraska at Omaha, HPER, Omaha 68182, USA. firstname.lastname@example.org
The purpose of this research was to determine the mRNA response to exercise in
different environmental temperatures. 9 recreationally active males (27±1 years,
77.4±2.7 kg, 13.5±1.5% fat, 4.49±0.15 L · min (-1) VO2 max) completed 3 trials
consisting of 1 h cycling exercise at 60% Wmax followed by a 3 h recovery in the
cold (7°C), room temperature (20°C), and hot (33°C) environments. Muscle biopsies
were obtained pre, post, and 3 h post exercise for the analysis of glycogen and
mRNA. Expired gases were collected to calculate substrate use. PGC-1α increased
to a greater degree in the cold trial than in the room temperature trial
(p=0.036) and the hot trial (p=0.006). PGC1-α mRNA was also higher after the room
temperature trial than the hot trial (p=0.050). UCP3 and MFN2 mRNA increased with
exercise (p<0.05), but were unaffected by temperature. COX was unaffected by
exercise or temperature. Muscle glycogen decreased with exercise (p<0.05), but
was no different among trials. Whole body VO2 was lower during exercise in the
cold than exercise in the heat. However, VO2 was higher during recovery in the
cold trial than in the room temperature and hot trials (p<0.05). This study
presents evidence of PGC-1α temperature sensitivity in human skeletal muscle.
© Georg Thieme Verlag KG Stuttgart · New York.
 J Appl Physiol (1985). 2006 Jul;101(1):12-3.
Tough love: left out in the cold, but not abandoned, by UCP3.
J Appl Physiol (1985). 2006 Jul;101(1):339-47.
There will never be peace in the world while there are animals in our bellies.