Tow-Int Tech Animal Metabolism Monitoring System Can Study the Effects of Systemic Metabolic Changes

Caused by Ambient Temperature on Tumor Immune Response

Background

Ambient temperature is related to our lives and has an important impact on human health. Recent studies have linked changes in environmental temperature to metabolism, gut microbes, and anti-cancer immune responses. Systemic metabolic changes induced by ambient temperature generate antitumor immune responses. Interactions between the gut microbiome and immunometabolism occur during temperature changes. Observing the effects of ambient temperature on body metabolism could help discover metabolic diseases and new treatments for cancer.

The animal metabolism monitoring system can not only detect ambient temperature but also monitor and record metabolic movement-related indicators of small animals in real time, qualitatively and quantitatively measure and analyze animal behavioral activities and their relationship with respiratory metabolism, and be widely used in nutrition, obesity, diabetes, and research on cardiovascular and other metabolic-related diseases.

How will systemic metabolic changes caused by ambient temperature affect the antitumor immune response?

1. Environmental temperature and fat metabolism

Differences in ambient temperature can affect an organism’s physical needs, metabolic activity, and gut microbiota. Adipose tissue is composed of a large number of clusters of fat cells, which are separated into lobules by thin layers of loose connective tissue. Glucose and lipid uptake are essential energy sources for cancer cells, and adipose tissue plays an important role in regulating energy balance during changes in ambient temperature.​​

Organisms' biophysical requirements at different environmental temperatures, including their metabolic activities in different tissues and intestinal microbiota, are different.

Muscle tremors will be triggered in a cold environment, promoting heat production in brown adipose tissue. Browning of white adipose tissue during prolonged cold exposure is also involved in thermogenesis through various mechanisms, including stimulation of hepatic FGF21 and bile acids (BA). Increased hepatic acylcarnitine metabolism contributes to lipid oxidation in the liver and other tissues.

In warm environments, heat exposure causes opposite changes in the microbiota, significantly benefiting bone remodeling through enhanced polyamine production. After hepatic heat adaptation, resting oxygen consumption decreases. As temperatures increase, white fat cells can undergo epigenetic reprogramming.

2. Immune response at different temperatures

Immune cells monitor and respond to environmental metabolic cues and various endogenous triggers, resulting in changes in their function. Human and animal studies have shown that varying environmental temperatures can alter cellular and humoral immune responses. The figure shows the metabolic and immune effects of ambient temperature in mice and humans

We know that immune cells are strengthened in a thermoneutral environment, and cold ambient temperatures have both inhibitory and supportive effects on the immune system, which, to a certain extent, depends on the duration of cold exposure. Several studies have also shown that although short-term cold stimulation reduces human lymphoproliferative responses and Th1 cytokine production, it also triggers inflammatory responses and immunosuppressive signature genes. Based on data from mice, long-term adaptation to cold exposure results in an anti-inflammatory response, suggesting that changes in immune responses during cold acclimation may be of general importance.

3. Effect of ambient temperature on intestinal microbiota

The human microbiome is distributed in various body parts, including the respiratory tract, skin, and intestines. Among them are many types of enteroviruses and fungi. In addition to the role of the intestinal microbiota in food digestion and host physiological regulation, increasing evidence suggests its protective immune role in enhancing anti-tumor immunotherapy in cancer patients.

The building blocks of life are inherently sensitive to temperature. When temperatures are too high, proteins denature, nucleic acids lose base pairing, and the plasma membrane becomes too fluid. When temperatures are too low, everything slows down: enzymes work less efficiently, nucleic acids form inconvenient secondary structures, and the plasma membrane stiffens. As a result, microorganisms and other organisms adjust their cellular processes to grow within specific temperature ranges and respond when their optimal temperature range is exceeded.

It is worth noting that although studies have shown that the microbiota under temperature acclimation plays an important role in host immune regulation, recent studies have highlighted that at the species level, humans and mice have different gut microbiota compositions. In humans, the phylum Bacteroidetes is primarily composed of the Firmicutes phyla of the families Bacteroidetesceae and Ruminococcaceae. In contrast, in mice, Bacteroidetes are mainly composed of the S24-7 family, while Firmicutes are composed of the Clostridiales. Based on these reports, different approaches can be imagined to overcome the challenges of using mouse microbiota as a surrogate for humans. Examples include establishing mouse models by transplanting human gut microbiota into germ-free mice and discovering functional homologs between mouse species and human microbiota. Although studies in animal models have shown that the microbiota plays a key role in regulating immunometabolism under different environmental temperatures, the importance of the human intestinal microbiota in this regard awaits further investigation.

4. Environmental temperature with cancer and immunotherapy

Environmental temperature may promote tumorigenesis through various physiological processes, such as metabolic and endocrine changes, changes in immune responses, and intestinal microbiota. Cancer and malignant cells undergo metabolic changes, primarily through accelerated glycolytic metabolism, to obtain energy to promote their proliferation, survival, and migration. However, glucose deficiency in the tumor microenvironment and the host environment can also lead to metabolic reprogramming of cancer cells, such as activating lipid metabolism, thereby altering tumor progression and drug resistance.

Chronic (mild) cold stress at a standard room temperature of approximately 22°C accelerates tumor growth; therefore, the efficacy of the anti-tumor immune response varies significantly depending on temperature. In a mouse model, a significant increase in anti-tumor effector CD8+ T cells was observed in the tumor microenvironment and draining lymph nodes, whereas both regulatory T cells and immunosuppressive cells were reduced at 30°C, suggesting that only rearing the mice at 22°C will result in significant suppression of the antitumor immune response. We also observed that this effect was lost if tumors grew in immunodeficient mice, suggesting a role for the adaptive immune response.

Improved immune monitoring is critical for cancer immunotherapy because it can increase the clearance of immune-mediated cancer cells. The gut microbiota produces a variety of small molecules and metabolites that play an integral role in the body's immune response and metabolic health. Increasing evidence supports the role of the gut microbiota in tumor growth, which influences the anti-tumor immunity and the efficiency of anti-cancer immune effects of various immune checkpoint inhibitors. Therefore, it is important to understand to what extent changes in the gut microbiota due to changes in environmental temperature are involved in cancer immunometabolism.

Conclusions

Ambient temperature changes affect antitumor immune responses. The interplay between the gut microbiome and immune metabolism also changes during temperature changes. Although it has recently become clear that alterations in the gut microbiota can lead to dysregulation of the immune system, the exact nature of this interaction remains to be determined. Profound studying the mechanisms of regulating immune responses by temperature-mediated interactions between adipose tissue and the microbiota may help elucidate therapeutic approaches for metabolic diseases and cancer.

Solutions 

Tow-Int Tech Animal Metabolism Monitoring System

The animal metabolism monitoring system independently developed by Tow-Int Tech is a highly flexible modular platform. Through one software, different functional modules in the cage can be controlled simultaneously, including the respiratory entropy metabolism monitoring module, environmental temperature control module, diet and weight monitoring module, urine/feces monitoring module, autonomous activity and training module, learning and memory monitoring module, and physiological telemetry monitoring module.

Functions

It can be used to monitor the oxygen consumption, CO2 production, respiratory, metabolic rate, etc., of animals and also contains an environmental temperature control module. The microcomputer program controls the temperature, humidity, and illuminance, which can simulate the temperature and humidity changes during the day and night, and can also select a sufficient and stable light source for the growth environment. It can meet the environmental requirements of different experiments, such as providing the required environmental conditions for detecting animal immune responses at different temperatures and providing different environmental conditions for the intestinal microbiome to help study the role of the microbiome in regulating immune metabolism at different environmental temperatures. Considering the functional homologs between mouse species and human microbiota, mouse models are generally established to study relevant human issues by analogy. The animal metabolism monitoring system monitors and records the metabolic movement-related indicators of small animals in real time for different mouse-specific models and provides a suitable experimental environment at the same time.

The optional parameters include energy consumption, food and water intake, feeding and drinking modes, spatial location, total activity and number of rotations of activity wheels, weight, heart rate, body temperature, automated behavioral analysis, etc. All data can be synchronized and stored on the computer.

Product Features 

Brand-new exterior design, convenient for daily experimental management and observation.

Experimental animals can be raised and monitored for a long time without being familiar with new environments.

Multi-channel measurement is adopted (the number of channels can be selected as needed), and each experimental chamber is equipped with independent controllers.

The high gas flow rate can prevent harmful gases such as carbon dioxide and ammonia from accumulating inside the cage, which can adversely affect animal physiology and cognition.

Built-in gas drying device to avoid water vapor affecting data accuracy and damaging gas analysis components.

Real-time monitoring records raw data without omission, preserving all possibilities for subsequent research.

Learn more about the Animal Metabolism Monitoring System

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Reference

Effects of temperature on immunometabolism regulation and cancer progression