PUT YOUR FAT TO WORK: WHITE VS BROWN FAT IN HEALTH AND METABOLISM

New research in the last decade has begun to challenge the traditional perspectives on fat mass. In-depth analysis reveals that there are three primary types of fat and that their deposits can serve different functions depending on their location in the body. Brown fat has become a particularly interesting area of study due to its potential to protect against cardiovascular and metabolic diseases, including diabetes.

The below article summarizes what is currently known about the biological functions of brown fat, how it differs from white fat, and how it may help in promoting overall health, optimal metabolism, and longevity.

Fat as a Highly Malleable Endocrine Organ

Fatty tissues were merely thought to be passive sites for fat storage. However, with insights from research, fat is increasingly being recognized as an underappreciated endocrine organ that actively influences many aspects of our biology.^[1]

Fat stores fuel for energy and hormone production, traps toxins, forms a core component of cell walls, insulates tissues (both in terms of temperature and from foreign materials), and secretes adipokines. Adipokines are hormones and other cellular signals produced by fatty tissue that are known to influence food intake, body temperature, energy metabolism, immune responses, and even cognitive function.

The malleability of body fat is usually at the epicenter of the benefits ascribed to weight loss and maintaining a healthy shape. Besides, due to the ability of fat to grow and shrink in size at a quicker rate compared to other tissues, fat is able to change form and exert different functional effects on overall metabolism. As fat is flexible, working with it is one of the most straightforward routes one can take to improve overall health and well-being.

Types of Fat in the Body

When most people think of losing weight, they are actually thinking of losing some of their white fat. Despite the bad reputation white fat has acquired over the years, along with body fat in general, there are other types of fat that can promote weight loss and counteract the negative impact of excess fat on health.

There are three types of fat in the body: white, brown and beige.

White Fat is the dominant form of fat found throughout the body. The main function of white fat cells (adipocytes) is to serve as a storage reservoir of fatty acids for the production of energy or other fatty substances across tissues. The cells found in White Adipocyte Tissue (WAT) are characterized by single giant vesicles that house fat and take up the bulk of the space inside the cell. These cells have very few mitochondria and thus have limited metabolic action. However, they do contribute substantially towards overall body metabolism through secreting hormones and immune signals. Excess WAT is known to be deleterious to health due to unbalanced cellular signaling that leads to chronic low-grade inflammation. WAT is present in subcutaneous and visceral deposits. Subcutaneous fat is more evenly dispersed across the body and is generally associated with better overall health than visceral fat, which is often linked to cardiometabolic problems.

Brown Fat is a different type of fat found in smaller amounts than WAT throughout the body. The primary function of Brown Adipose Tissue (BAT) is to generate heat (thermogenesis) and maintain optimal body temperature during exposure to cold. BAT cells are characterized by many small vesicles that contain fat, as well as multiple mitochondria that are specially adapted to burning fat in order to generate energy (ATP) and heat. Like WAT, BAT secretes hormones known as batokines that exert numerous effects on overall metabolism.^[2] Infants have the highest concentrations of BAT that decline through the course of development. Adults have far less brown fat, which is theorized to be an adaptation to wearing clothing where thermogenesis becomes less of a requirement. It is believed that brown fat can regenerate due to the discovery of several BAT stem cell precursors.^[3] Out of all types of fatty tissue, BAT appears to have the highest number of stem cell lines that are each specific to the body area where BAT is found. This suggests that BAT deposits differ from one another, potentially due to differences in heat requirements across various bodily compartments.

Beige Fat, also referred to as brite (brown in white) fat, is found interspersed throughout WAT. The cells in beige fat are lighter than those seen in BAT, with slightly larger fat vesicles and marginally fewer mitochondria. These fat cells are regarded as an intermediate type of cell between white and brown fat cell types. They have the ability to burn fat and generate heat. WAT can be converted into beige fat during cold exposure, which is a process known as browning (of white fat). In test-tube studies, browning has proven to be a reversible process, which indicates that beige fat serves an important function in terms of adaptation to cold environments. Beige fat can also be generated from its own unique stem cell precursors, suggesting that WAT is not a requirement and that there might be specific mechanisms that influence browning in WAT tissue. Like BAT, beige fat also secretes batokines that can affect overall metabolism. When BAT is low as a result of atrophy or aging, beige fat can be recruited in WAT to fulfill the same thermogenic and metabolic functions.^[4]

How Brown Fat Generates Heat and Why It’s Important

Neurologic Control of Thermogenesis. Brown and beige fat generate heat through stimulation from the sympathetic nervous system or through the activation of cold-sensing cell receptors. Sympathetic nervous system activation of thermogenesis tends to occur in response to signals from the thalamus in the brain, which travel along the spine, right to where BAT is predominantly located.^[5] The thalamus and hypothalamus constantly interpret chemical signals from the bloodstream and nervous system to coordinate bodily functions vital for survival.

Thermoregulation through the Skin. The skin and blood vessels are particularly important sites for temperature control. The blood plays a role in distributing temperature evenly throughout the body. When the core temperature becomes too high, blood vessels that pass through the skin expand to allow for heat to escape more easily. When the skin is exposed to cold, the blood vessels contract, limiting heat escape. Experimental studies show that cold exposure can initiate BAT thermogenesis without brain involvement through cold receptors on the skin. In healthy individuals, the skin also houses the largest deposits of WAT and beige fat, which are both naturally involved in temperature regulation.

Thermogenesis Regulates Metabolism. Maintaining optimal body temperature is important for the majority of cellular chemical reactions and processes, including energy generation. As a result, core body temperature can be seen as a reflection of cellular metabolism. All cells typically generate heat due to a slight energy handling “inefficiency”, where some energy is lost to heat during cellular respiration. The heat from cells increases in tandem with core body temperature and overall metabolic rate. Thus, a lower metabolic rate is reflective of a lower core body temperature. Interestingly, the lower the metabolic rate, the more efficient energy production is in the cell. Yet, if the body’s core temperature becomes too low, cells cannot generate energy properly. In this respect, temperature control is a tightly regulated process in which brown and beige fat play a significant role.

Thermogenic Cues. Heat generation is initiated in response to injury, infection, stress, changes in metabolic markers (such as sleep^[6], hypoglycemia and the fasting state), and cold temperatures, including the environment or ingested foods and beverages.

6 Potential Health Benefits of Brown Fat Mass

Brown fat has many metabolic functions similar to that of muscle tissue that serve to enhance overall health in the following ways:

1. Brown and Beige Fat Keep White Fat in Check. During heat generation, the size of the fat vesicles inside BAT cells shrinks. Fat and branched-chain amino acids from the diet or bodily reserves are mobilized to replenish BAT fat reserves, helping BAT to regulate excessive fat accumulation as well as protein dysmetabolism.^[7] Similarly, beige fat also contributes towards heat generation by promoting the breakdown and use of fats stored in WAT. As WAT is a precursor to beige fat, browning can potentially regulate WAT levels in the body. This, in itself, can promote weight loss and its associated benefits, including a lower risk for cardiometabolic diseases.
2. Improves Insulin Sensitivity. In a small group of patients with diabetes exposed to cold temperatures, BAT-induced thermogenesis was proven to enhance insulin sensitivity by as much as 43% over the course of 10 days^[8]. Other small-scale human trials and animal studies have confirmed that BAT activation and heat generation reduce insulin resistance, increase insulin receptor expression, and promote insulin sensitivity. Upon closer inspection, BAT thermogenesis does not appear to increase blood glucose consumption or alter insulin signaling directly. Instead, these effects are mediated through the factors that BAT secretes, including BAT-specific interleukin-6^[9] and FGF21 (Fibroblast Growth Factor 21)^[10].
3. Enhances Cardiovascular Profile. A handful of studies have shown that BAT activity is associated with a better cardiovascular profile in humans and animals. In humans, BAT is linked with a lower risk of developing obesity, dyslipidemia, and related cardiovascular metabolic diseases, including diabetes, cerebrovascular disease, coronary artery disease, and hypertension. Furthermore, BAT heat generation during acclimation to cold temperatures has also been linked with increases in HDL cholesterol, reductions in LDL cholesterol, and lower atherosclerosis risk. Several batokines are believed to be responsible for these effects. One in particular (12,13 diHOME) has been shown to improve energy production in heart cells as well as left ventricular function, which is known to decline with age and during the course of various cardiovascular diseases.
4. Cognition. While there is limited evidence that highlights a direct link between BAT, beige fat, and improved cognitive function, BAT has been associated with protecting against reduced cognition associated with Alzheimer’s Disease^[11] and obesity in animal studies. In obese mice, beige fat transplantation into skin WAT was associated with improved functioning and plasticity in the hippocampus^[12]. This was attributed to the induction of anti-inflammatory compounds released from lymphocytes residing in the meninges of the brain, which counteracted the inflammatory effects of WAT that are known to affect optimal cognition. More research is required before it can be known whether higher levels of beige fat are able to counteract other types of neuroinflammation and indirectly enhance overall cognition.
5. Immune Function. Brown and Beige fat reserves are responsible for generating a fever during an active infection, mediating one of the body’s core defense mechanisms against pathogens. Batokines also exert effects on immune cells, most of which are still an active area of investigation. Two batokines have recently been noted to recruit macrophages into BAT as well as to reduce their expression of inflammatory markers during thermogenesis. In light of this, BAT may help to promote improved immune function, particularly during an active fever.
6. Potentially Liver Protective. Preliminary studies on mice suggest that BAT is responsible for disposing of excess liver succinate, a by-product of cellular respiration. Succinate accumulation is associated with increased inflammation and tumor formation. BAT activation prevents its accumulation by promoting the generation of heat.^[13]

Factors that Promote Brown Fat Production and Thermogenesis

Brown fat function and beige fat production can be stimulated by the following:

• Cold Exposure is perhaps the most obvious stimulator of BAT thermogenesis, whether the source is environmental or dietary. Exposure to cold has been shown to increase fatty acid uptake into BAT, resulting in heat generation and lower levels of circulating triglycerides^[14]. BAT and beige fat express more vascular growth factors in cold environments, which lend to their growth and maintenance. Cold exposure promotes gut microbe changes that have been associated with optimal BAT function and the browning of WAT tissue. Exercising in the cold has been shown to enhance these effects more than either cold or exercise alone^[15]. It should be noted that excessive or extreme cold exposure can detract from BAT-induced thermogenesis as well as optimal health and well-being (see ‘Brown Fat Side Effects’ below).
• Exercise induces thermogenesis independently of BAT by increasing energy production and the metabolic rate. However, exercise is known to promote the browning of WAT through the release of myokines. However, excessive exercising is known to detract from WAT browning, as seen in athletes, likely due to other thermogenic adaptations and the lower percentage of body fat. Batokines from beige fat and BAT appear to enhance exercise by promoting an increase in fatty acid uptake into skeletal muscle. Exercising in the cold seems to have the added benefit of cold-derived batokines that simultaneously promote glucose uptake into muscle tissue and enhance muscle exercise capacity^[16], suggesting that exercising in the cold may be optimal.
• Dietary Nutrients. Many plant-based phytochemicals have been shown to promote thermogenesis in BAT or the browning of WAT tissues in experimental studies. This supports the notion that a nutrient-dense diet can facilitate optimal BAT function. Nutrients known to enhance BAT and beige fat typically affect receptors involved in stimulating heat as well as promoting better energy metabolism and mitochondrial function. Examples include menthol^[17], capsaicin, quercetin^[18], naringenin^[19], daidzein^[20], curcumin, and berberine, all of which promote WAT browning and thermogenesis in BAT and beige fat. Resveratrol, green tea catechins, caffeine, and cacao polyphenols have also been shown to promote thermogenesis in BAT.
• Microbiome. The gut microbiome is involved in promoting BAT function and WAT browning. Studies show that exercise and cold invoke microbial changes that facilitate these enhancements. BAT and beige fat also respond to short-chain fatty acids (specifically lactate and butyrate) produced by friendly gut bacteria in the colon. Short-chain fat levels can be encouraged by consuming a diet high in fermentable fiber, which also serves to regulate the gut microbiome, enhance digestion and promote optimal absorption of nutrients.
• Caloric Restriction and Lower Blood Glucose Levels. Caloric restriction in both rat and in vitro studies has been shown to enhance the activity of BAT as well as protect it from age-related decline.^[21] Additionally, intermittent fasting has been shown to promote the browning of WAT tissue in mice^[22]. Lowering daily caloric intake in the absence of malnourishment is linked with better mitochondrial efficiency, more stable energy levels, and a reduced risk of developing hyperglycemia and insulin resistance. As BAT is known to generate heat in response to hypoglycemia, which increases the release of batokines and facilitates optimal fat breakdown for energy production, it is likely that the blood glucose-lowering effects of caloric restriction also contribute towards promoting BAT activity and WAT browning.
• Circadian Signaling, Light, and Seasonal Variance. Seasonal studies in humans have shown that brown fat tissue levels increase during winter when light and temperature conditions are lower. In Summer, BAT levels decline and are less active. BAT is thought to be more responsive to light as a cue than heat^[23], suggesting that circadian signaling and light exposure play a crucial role in regulating body temperature. This is reflected during sleep, where BAT becomes active (usually in the dark) in response to a lower metabolic rate and reductions in core body temperature. BAT also may enhance fat-derived energy production during sleep and the fasting state. Test-tube and animal studies show that vitamin D3 (the “sunlight” hormone) reduces the browning of WAT (as needed during Summer) yet enhances and partially regulates fat-burning in BAT^[24], as well as BAT mitochondrial regeneration (biogenesis)^[25]. Vitamin D deficiency is also associated with increased WAT levels, suggesting that it is required to regulate overall body fat metabolism.^[26]
• Physiological Stress. Stress signaling in the body, including adrenergic neurotransmission and glucocorticoids (stress hormones), are intimately involved in activating BAT and promoting browning of WAT. These are the main mechanisms underlying the beneficial effects of cold exposure and exercise on these tissues. Early life stress has been linked to lower WAT and a higher percentage of BAT in adult mice. However, despite these results, mice exposed to early life stressors were more prone to developing obesity and larger WAT deposits when consuming a Western-style diet high in fat and highly processed foods.^[27]

Factors that Detract from Brown Fat Function

There are far fewer factors that detract from BAT than those promoting it. These include:

• Chronic Inflammation and Excessive WAT. While BAT is known to promote the breakdown of fat and reduce inflammation levels, excessive fat in WAT can inhibit BAT function through chronic low-grade inflammation. Furthermore, excessive fat can promote inflammation in BAT, similar to WAT. Body inflammation from other sources may also increase WAT production and lead to impaired BAT function. This highlights the importance of leading a healthy lifestyle, exercise, and optimal dietary nutrition for optimizing BAT function, as BAT and beige fat alone are not enough to counteract the effects of obesity, disease, or chronic low-grade inflammation.
• Ambient Heat and Light Exposure. BAT becomes less active in the warmer months of the year, while some beige fat typically undergoes a transformation back towards WAT. Research has shown that beige adipocytes retain the memory of the environmental changes in light and temperature, capable of converting to WAT and back throughout the year. This is a natural adaptation to prevent excessive thermogenesis, highlighting the essential nature of maintaining a balanced fat mass. There appear to be larger, more stable depositions of interconvertible beige fat in subcutaneous and thigh fat. ^[28]

Brown Fat Side Effects: Is There Such a Thing as Too Much?

Research has not honed in enough on the effects of excessive BAT or beige fat accumulation or whether an excess is even possible.

Optimal BAT Levels Are Likely to be Inter-Individual. As the major function of BAT is heat generation, more of it will be required in cold environments than in hot environments. A few studies have shown that different ethnic populations are better suited to cold environments than others due to containing a higher percentage of BAT, as well as more activity in BAT when exposed to the same cold climate.^[29] Furthermore, women hold more fat mass than men on average, especially subcutaneous fat known to hold a larger percentage of BAT. Thus, BAT levels are regulated differently across the global population, with genetics, gender, and the environment dictating what optimal BAT ought to be on an individual basis.

Excessive BAT May Promote States of Disease. As BAT typically declines with age, it is not likely to become excessive throughout one’s lifetime. Excessive beige fat accumulation could theoretically contribute to various disease states that are indicative of fat and muscle wasting, such as cancer-related cachexia^[30]. Browning of WAT occurs excessively in response to major traumatic injuries, including severe burn wounds^[31], surgery, and sepsis. In these scenarios, BAT and beige fat contribute to extreme muscle and fat wasting.

Balanced BAT Activity is Optimal. Like exercise, BAT activity can be regarded as a positive physiological stressor. Despite its known benefits, the action of BAT needs to be kept balanced to avoid adverse health effects. In the absence of WAT, promoting BAT is not likely to be as beneficial, suggesting that a ratio of BAT:WAT is required for optimal well-being. Excessive cold exposure has been linked with an increased risk for atherosclerosis in mice (who have more BAT on average)^[32] due to compensatory mechanisms that promote an increase in fat and cholesterol production for thermogenesis. This increases the chances of fat deposition in the blood vessel walls as well as liver fat accumulation.^[33]

Batokines in the Gut May Promote Inflammation. Studies indicate that bacteria are capable of secreting similar compounds to batokines and that some of them have been linked with allergy, asthma, and intestinal inflammation^[34]. Nevertheless, it is uncertain whether bacterial-derived “batokines” function the same as actual batokines, i.e., whether the body might excrete excessive batokines into the gut for disposal or whether they may pose similar effects to their bacterial-derived counterparts. These findings pave the way for future investigation into the potential detrimental effects of BAT, if any.

Conclusion

Brown fat is a vital endocrine organ that exerts many beneficial effects on overall health. The effects of brown and beige fat are similar to that of muscle in that they make use of excess fat and amino acids and secrete hormonal factors that regulate energy metabolism. Enhancing brown fat activity and maintaining healthy brown fat levels may lower the risk of developing metabolic diseases and conditions associated with aging. Brown fat keeps white fat levels in check and is predominantly active in the cold. Exercise, dietary plant-based nutrients, and healthy lifestyle considerations improve the function of brown fat as well as promote optimal beige fat conversion from white fat.

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