How Mammals Generate Heat: A Deep Dive
Explore how mammals keep warm through unique fat mechanisms.
Yelina Manandhar, Anita Pirchheim, Peter Hofer, Nemanja Vujic, Dagmar Kolb, Gerald Hoefler, Dagmar Kratky, Martina Schweiger, Ulrike Taschler, Robert Zimmermann, Rudolf Zechner, Renate Schreiber
― 6 min read
Table of Contents
- How Do We Get Energy for Heat?
- The Mystery of UCP1
- Investigating the Role of Lipases in Brown Fat
- Changes in Body Temperature During Cold Exposure
- The Impact of Food Intake on Energy Metabolism
- The Role of Inguinal White Adipose Tissue
- Consequences of Losing Both ATGL and HSL
- Understanding the Bigger Picture
- Concluding Thoughts on Fat and Thermogenesis
- Original Source
Mammals are warm-blooded creatures, meaning they can keep their body temperature stable even when the outside environment changes. This amazing skill is called temperature homeostasis. When it's cold outside, our bodies have clever ways to stay warm, like reducing blood flow to the skin, making our hairs stand up, and even shivering.
But here's the twist: when mammals are exposed to cold for days or weeks, they find another way to produce heat, especially in specific types of fat cells. These cells, called brown and beige adipocytes, can generate heat from stored energy without the need to shiver. This is known as non-shivering thermogenesis (NST). The key player in this process is a special protein called uncoupling protein 1 (UCP1), which lets cells turn energy into heat instead of storing it as ATP, the energy currency of the cell.
How Do We Get Energy for Heat?
NST is spurred on by various fuels circulating in our bodies, such as glucose and fatty acids. These fuels are like the gas in a car, giving our bodies the energy boost they need to keep warm. Interestingly, when we have more active brown fat tissue, we often see improvements in how our bodies manage sugars and fats. This might even lead to better heart health!
The Mystery of UCP1
The UCP1 protein has been around since the 1980s, but our knowledge of its structure is relatively recent. Yet, the full story of how UCP1 works remains a puzzle. We know that long-chain fatty acids activate UCP1, and these fatty acids generally come from breaking down stored fats in our bodies. Two important enzymes, called ATGL and HSL, are responsible for this fat breakdown.
When it's cold outside, our nerves send signals that trigger the release of special hormones. These hormones activate receptors in brown fat cells, which then kick off a series of events leading to increased energy production and heat generation. Surprisingly, some research has shown that even without the activity of ATGL, animals can still maintain their body temperature and produce heat through NST.
Investigating the Role of Lipases in Brown Fat
To dig deeper into how these processes work, scientists created a special mouse model that lacks both ATGL and HSL in brown fat. They wanted to see if these mice could still produce heat when exposed to cold temperatures. To their surprise, these "BAT-iDAKO" mice managed to keep warm, raising questions about what exactly was fueling UCP1.
While the mice seemed to do fine, the studies revealed that the lack of ATGL and HSL reduced the overall ability of brown fat to generate heat when exposed to cold. Even though the number of brown fat cells increased, the amount of mitochondria in those cells, which are crucial for energy production, was low.
Another twist in this tale involved the white fat tissue located near the brown fat. It turned out that the white fat tissue was able to pick up the slack by producing more heat, compensating for the dysfunctional brown fat. However, when both lipases were missing from all fat tissues, the mice were not able to keep warm anymore.
Changes in Body Temperature During Cold Exposure
When researchers measured the body temperature of the BAT-iDAKO mice during cold exposure, they found something interesting. The mice maintained a slightly higher core body temperature compared to their normal counterparts, suggesting they were managing pretty well despite lacking key enzymes in their brown fat.
However, the study did not just stop at body temperature. It also looked at the energy consumption rates of these mice in cold conditions. Both the BAT-iDAKO and the control mice showed similar energy consumption when given a special drug to stimulate energy use. This indicated that the non-shivering thermogenesis was functioning just fine in the absence of fat breakdown in the brown fat.
The Impact of Food Intake on Energy Metabolism
The BAT-iDAKO mice showed some changes in their overall metabolism. They had a higher rate of carbohydrate use during the day, suggesting they were relying more on sugars for energy instead of fats. This was accompanied by increased food intake during the daytime, but their nighttime eating habits remained the same as before. Interestingly, their physical activity levels did not change, showing that they were not just sitting around eating all day.
On a cellular level, the researchers noticed that the brown fat from the BAT-iDAKO mice had a hodgepodge of cells, including inflammation and fibrosis, which means there was a sort of scarring happening. This was different from the normal-looking brown fat.
The Role of Inguinal White Adipose Tissue
With the brown fat not doing its job effectively, researchers turned their attention to the inguinal white adipose tissue (ingWAT). To their surprise, the ingWAT in the BAT-iDAKO mice had transformed quite a bit. The white fat began to produce UCP1, the very protein they were studying. This browning of white fat allowed it to help maintain body temperature when brown fat was less effective.
The ingWAT from BAT-iDAKO mice showed an increase in mitochondrial function and energy substrate uptake, which meant this fat was stepping up to take over some of the thermogenic duties during cold exposure.
Consequences of Losing Both ATGL and HSL
In another experiment, researchers created a model where both ATGL and HSL were knocked out across all adipose tissues. The results were starkly different. These mice, dubbed the DAKO mice, could not sustain non-shivering thermogenesis at all, leading to impaired temperature regulation in the cold.
Unlike the BAT-iDAKO mice, the DAKO mice showed a dramatic reduction in their ability to generate heat, leading to a significant drop in core body temperature during cold adaptation. Despite this, they, too, managed to maintain their body temperature through other systemic adaptations.
Understanding the Bigger Picture
These experiments have revealed that while brown adipose tissue (BAT) plays a crucial role in temperature regulation and energy metabolism, other fat tissues like white adipose tissue can take over when needed. This flexibility highlights a fascinating backup system in our bodies.
While it may seem like a complicated series of events, when it comes to staying warm, our bodies have a few tricks up their sleeves. Whether it is through brown fat heating us up with stored energy or white fat stepping in to save the day, the science behind our warmth is both impressive and a bit funny when you think about it-like having a backup generator for when your main power source decides to take a cold day off!
Concluding Thoughts on Fat and Thermogenesis
In conclusion, brown and white fat are like a duo working together to keep us warm. While brown fat is the star of the show with its heat-generating abilities, white fat can come to the rescue when needed. The studies with BAT-iDAKO and DAKO mice show just how adaptable our bodies can be, especially when it comes to temperature regulation.
Next time you feel a chill in the air, spare a thought for the incredible mechanisms at play inside your body. After all, it’s not just you who has to layer up in the cold; your body is doing its own version of “dress for success” with fat!
Title: Non-shivering thermogenesis is intact upon brown-adipocyte specific loss of ATGL and HSL due to white adipose tissue browning
Abstract: Intracellular fatty acids (FAs) activate and fuel non-shivering thermogenesis (NST) mediated via uncoupling protein 1 (UCP1). Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the two main triacylglycerol lipases in adipocytes that control FA availability. We showed previously that a brown adipocyte-specific loss of ATGL does not affect cold-induced thermogenesis in brown adipose tissue (BAT) and NST, raising the question whether HSL-mediated FA release is sufficient to allow NST. Here, we show that a brown adipocyte-specific loss of both ATGL and HSL in mice leads to impaired BAT thermogenic capacity in cold, but still allows normal NST. The BAT defect is attributed to an impaired abundance of mitochondria as well as reduced oxidative capacity despite increased adipocyte numbers in BAT. Notably, the reduced thermogenesis in BAT of BAT-iDAKO mice leads to a concomitant upregulation of UCP1 expression (browning) in white adipose tissue (WAT) indicating that thermogenesis partially shifts from BAT towards WAT. In accordance with this assumption, genetic loss of ATGL and HSL in both BAT and WAT leads to dysfunctional BAT thermogenesis and defective browning in WAT resulting in blunted NST. Our study highlights the metabolic adaptability of adipose tissue and the critical role of intracellular lipolysis in the regulation of thermogenesis.
Authors: Yelina Manandhar, Anita Pirchheim, Peter Hofer, Nemanja Vujic, Dagmar Kolb, Gerald Hoefler, Dagmar Kratky, Martina Schweiger, Ulrike Taschler, Robert Zimmermann, Rudolf Zechner, Renate Schreiber
Last Update: 2024-12-05 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.04.626093
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.04.626093.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.