Post by Anirudha Agnihotry:

Briefly? Running in cold could possibly consume more energy. How does ambient temperature affect our energy utilization (metabolism)? A detailed look at the players and process even suggests a relatively painless approach to counter obesity! Let’s see how.

Before proceeding further, here’s a handy definition list to better understand the physiology of energy utilization, especially since the field is awash with jargon and many acronyms.

From 1

Not just plain vanilla, body fat comes in more than one flavor

Body fat, a major player in energy utilization, has at least two varieties, white (White Adipose Tissue, WAT) and brown (Brown Adipose Tissue, BAT). Found in different areas of the body,

From 2

WAT and BAT also have very different, almost diametrically opposite, metabolic features.

From 3

Recent mouse model research (4) even added a third fat flavor, beige/’brite’, which is induced ‘brown in white’ fat.

How ambient temperature, fat and energy expenditure intersect

How are energy expenditure and fat type related? Simply put, WAT stores energy, BAT spends it.

How does BAT do this? BAT adipocytes (fat cells) express a unique gene, SLC25A7, which encodes the mitochondrial uncoupling protein 1 (UCP1) (5). ‘Embedded in the inner mitochondrial membrane, UCP1 acts as a proton conduit from the inter-membrane space to the mitochondrial matrix. Activation of UCP1 leads to the energy generated by the electron transport chain and stored in the pH and electrochemical gradient across the inner mitochondrial membrane to be dissipated as heat, rather than used to fuel ATP generation by ATP-synthase‘ (6). Thus, BAT converts lipid-derived chemical energy into heat (thermal energy).

Till recently, we thought that BAT depots were only physiologically relevant in small mammals and human infants (7, 8), even though we knew for decades that adult humans also have BAT (7). That is, until a 2009 study (9). This study showed that

  1. BAT activity was present in 23 of 24 healthy adult men.
  2. But only when they were exposed to cold temperature.
  3. Even overweight and obese men have BAT, though significantly lower in activity compared to lean men.

Other independent studies (10, 11, 12, 13, 14, 15, 16, 17, 18) also confirmed

  1. Adult humans have metabolically active BAT.
  2. Obese and older people have less metabolically active BAT.
  3. BAT activity negatively correlates with BMI (Body Mass Index), i.e. higher BAT activity, lower BMI.

More clues that adult human BAT could be physiologically relevant?

  1. It’s highly innervated and vascularized (19).
  2. Its metabolic activity is partly controlled by norepinephrine secretion by the sympathetic nervous system (SNS) (20). Actually, adult human BAT is likely more accurately beige/brite (21, 22).
  3. A genetic association study found a UCP1 promoter polymorphism that reduces its expression and is associated with a higher BMI and abdominal obesity (23).

Thus, BAT could be a target for obesity treatment.

Summary of human BAT studies*
* Caveat to human active BAT studies: Only 18F-fluorodeoxyglucose PET-CT (positron emission tomography with computed tomography) (FDG PET-CT) unequivocally identifies human adult active BAT. Most commonly used routinely in cancer diagnostics for cancer staging, such scans use ionizing radiation, and are not possible to use in large numbers of healthy human adults. Thus, most data on active human BAT is from cancer staging studies.

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How does cold exposure increase basal metabolic rate (BMR)? By activating BAT and NST

What happens when we are abruptly exposed to cold? Receptors in our skin sense the cold, and our muscles shiver, i.e. we spend energy to generate heat (thermogenesis) (24). Called Shivering thermogenesis (ST), this is a short-term protection against hypothermia. It’s uncomfortable and makes our movements uncoordinated.

In 1961, research (25) first showed that in healthy adult men exposed to prolonged cold (12oC for 8 hours a day for 31 days), ST is replaced by non-shivering thermogenesis (NST). More recent research shows chronic cold stimulation activates BAT and increases NST (26, 27), and crucially, the first study (26) found that NST increases through BAT, and not skeletal muscle, activity. NST increase can also happen naturally through seasonal changes. For example, in Netherlands with a mild temperate climate, cool summers and mild winters, though most people spend most time in ambient temperature-controlled indoors, their winter NST is significantly higher compared to summer (28). Research also shows seasonal variation in cold-activated BAT (12).

Lower the ambient temperature and induce active BAT. An obesity therapeutic?
Since the 20th century, especially in developed countries, our indoor temperature is engineered to maximize our comfort and minimize the energy our body expends to maintain our body temperature. At the same time, we spend about 90% of our time indoors. Our recent greater control of ambient indoor temperature means we experience a predominantly narrow temperature range indoors. This range of temperature called the Thermoneutral zone (TNZ) is where we maintain our body temperature without much effort, effort defined as heat production or as sweat. The big deal about this? When we chronically consume more energy and spend less, we store the excess energy as fat (white adipose tissue; WAT). Result? Obesity. Does self-controlled ambient temperature contribute to obesity propensity? If yes, what could we do to counter it?

The temperature range at which we feel comfortable, our Thermal comfort zone (TCZ) is broader than TNZ, and we can tolerate and adapt to broader temperature ranges without feeling obvious discomfort (29, 30).

From 1

As this figure shows, there seems to be a sweet spot where we could increase our basal metabolic rate (BMR) simply by decreasing our ambient temperature. Why sweet spot? Because we let our gradual acceptance of a lower ambient temperature induce BAT, which increases our BMR, and we stay comfortable since we do this through NST, not ST. Dr. Wouter van Marken Lichtenbelt calls this ‘temperature training‘. An associate professor in the department of human biology at Maastricht University Medical Center in the Netherlands, he studies the interplay between ambient temperature, body fat and energy utilization. In his words, ‘What would it mean if we let our bodies work again to control body temperature?‘ (1).

A simplified and not simplistic summary?
Acclimation to cooler than normal ambient temperature —> our BAT depots and BAT metabolic activity increase —> we expend greater heat through NST—> we increase our BMR*.

* Caveat?  van Marken Lichtenbelt’s team (31) could not use this process to explain energy expenditure differences in an unusual pair of monozygotic Dutch twins with very different lifestyles. One twin is famously known as the Iceman, and holds several world records ‘withstanding extreme cold exposure under several disciplines, such as the fastest half- marathon on snow and ice while barefoot, and the longest duration while fully immersed in crushed ice (1 hour and 50 minutes)’. Though the other twin leads a normal ‘sedentary’ lifestyle, both brothers practice ‘a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity‘.

Implication? While the positive correlation between BAT activity, NST and BMR sounds beguilingly plausible and could be used to counter obesity, it may not yet be ready for prime time since we apparently still have major gaps in understanding the full picture of energy expenditure at different temperatures.

As for running in the cold, all this research suggests acclimating to mild cold (down to 17oC) should increase energy expenditure, while the same may not be the case for running in warm and humid as BMR increase is not as steep (last figure above), especially in the narrow range of higher temperatures likely to be tolerable.

Bibliography

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  2. Awada, Rana, Avinash Parimisetty, and Christian Lefebvre d’Hellencourt. “Influence of Obesity on Neurodegenerative Diseases.” (2013). Page on intechopen.com
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  4. Harms, Matthew, and Patrick Seale. “Brown and beige fat: development, function and therapeutic potential.” Nature medicine 19.10 (2013): 1252-1263. Page on researchgate.net
  5. Palmieri, Ferdinando. “The mitochondrial transporter family (SLC25): physiological and pathological implications.” Pflügers Archiv 447.5 (2004): 689-709.
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  14. Muzik, Otto, Thomas J. Mangner, and James G. Granneman. “Assessment of oxidative metabolism in brown fat using PET imaging.” Frontiers in endocrinology 3 (2012). Assessment of Oxidative Metabolism in Brown Fat Using PET Imaging
  15. Ouellet, Véronique, et al. “Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans.” The Journal of clinical investigation 122.2 (2012): 545. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans
  16. Vijgen, Guy HEJ, et al. “Brown adipose tissue in morbidly obese subjects.” PloS one 6.2 (2011): e17247. Brown Adipose Tissue in Morbidly Obese Subjects
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  18. Pfannenberg, Christina, et al. “Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans.” Diabetes 59.7 (2010): 1789-1793. Impact of Age on the Relationships of Brown Adipose Tissue With Sex and Adiposity in Humans
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Thanks for the A2A, Anonymous.

How does weather affect energy utilization in the human body?

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