Brown adipose tissue/brown fat

https://www.nejm.org/doi/10.1056/NEJMcibr0809610

**created June 2021**

Brown adipose tissue, or brown fat, is a type of fat cell that converts energy into body heat when food is eaten and digested, as opposed to white adipose tissue, or white fat, that is more plentiful and accumulates in noticeable parts of the body (for example, the belly) when too many calories are consumed and too few are expended through exercise. White fat is essential for human beings, it provides an energy reserve and insulates and cushions internal organs. Too much accumulating white fat can lead to diseases and poor health. More brown fat is tied to a lower disease risk and better health. Brown adipose tissue is most prevalent in hibernating animals and human babies but can be found in adult humans as well.
 
What does research say about brown adipose tissue/brown fat (these articles have been added to the Science Primary Literature database):
 
*Bartelt, A., & Heeren, J. (2014). Adipose tissue browning and metabolic health. Nature Reviews. Endocrinology, 10(1), 24-36. [Cited by]
 
“Accumulation of excess white adipose tissue (WAT) has deleterious consequences for metabolic health. The activation of brown adipose tissue (BAT), the primary organ for heat production, confers beneficial effects on adiposity, insulin resistance and hyperlipidaemia, at least in mice. As the amount of metabolically active BAT seems to be particularly low in patients with obesity or diabetes mellitus who require immediate therapy, new avenues are needed to increase the capacity for adaptive thermogenesis. In this light, we review the findings that BAT in human adults might consist of not only classic brown adipocytes but also inducible brown adipocytes (also called beige, brown-in-white, or brite adipocytes), which are phenotypically distinct from both white and brown adipocytes. Stimulating the development of beige adipocytes in WAT (so called ‘browning’) might reduce adverse effects of WAT and could help to improve metabolic health. This article focuses on the development and regulatory control of beige adipocytes at the transcriptional and hormonal levels. Emerging insights into the metabolic role of beige adipocytes are also discussed, along with the developments that can be expected from these promising targets for therapy of metabolic disease in the future.”
 
*Becher, T., Srikanth, P., Kramer, D. J., Mahmoud, E., Marx, S. J., Wibmer, A. G., . . . Cohen, P. (2021). Brown adipose tissue is associated with cardiometabolic health. Nature Medicine, 27(1), 58-65. [PDF] [Cited by]
 
White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography–computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health.”
 
*Gavaldà-Navarro, A., Villarroya, J., Cereijo, R., Giralt, M., & Villarroya, F. (2021, March 12). The endocrine role of brown adipose tissue: An update on actors and actions. Reviews in Endocrine & Metabolic Disorders.
 
“In recent years, brown adipose tissue (BAT) has been recognized not only as a main site of non-shivering thermogenesis in mammals, but also as an endocrine organ. BAT secretes a myriad of regulatory factors. These so-called batokines exert local autocrine and paracrine effects, as well as endocrine actions targeting tissues and organs at a distance. The endocrine batokines include peptide factors, such as fibroblast growth factor-21 (FGF21), neuregulin-4 (NRG4), phospholipid transfer protein (PLTP), interleukin-6, adiponectin and myostatin, and also lipids (lipokines; e.g., 12,13-dihydroxy-9Z-octadecenoic acid [12,13-diHOME]) and miRNAs (e.g., miR-99b). The liver, heart, and skeletal muscle are the most commonly reported targets of batokines. In response to BAT thermogenic activation, batokines such as NRG4 and PLTP are released and act to reduce hepatic steatosis and improve insulin sensitivity. Stress-induced interleukin-6-mediated signaling from BAT to liver favors hepatic glucose production through enhanced gluconeogenesis. Batokines may act on liver to induce the secretion of regulatory hepatokines (e.g. FGF21 and bile acids in response to miR-99b and PLTP, respectively), thereby resulting in a systemic expansion of BAT-originating signals. Batokines also target extrahepatic tissues: FGF21 and 12,13-diHOME are cardioprotective, whereas BAT-secreted myostatin and 12,13-diHOME influence skeletal muscle development and performance. Further research is needed to ascertain in humans the role of batokines, which have been identified mostly in experimental models. The endocrine role of BAT may explain the association between active BAT and a healthy metabolism in the human system, which is characterized by small amounts of BAT and a likely moderate BAT-mediated energy expenditure.”
 
*Suárez-Zamorano, N., Fabbiano, S., Chevalier, C., Stojanović, O., Colin, D. J., Stevanović, A., . . . Trajkovski, M. (2015). Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nature Medicine, 21(12), 1497-1501. [PDF] [Cited by]
 
Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient ( ob/ob ) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.”
 
*Wang, Z., Wang, Q. A., Liu, Y., & Jiang, L. (2021, May 24). Energy metabolism in brown adipose tissue. The FEBS Journal. [PDF]
 
Brown adipose tissue (BAT) is well known to burn calories through uncoupled respiration, producing heat to maintain body temperature. This ‘calorie wasting’ feature makes BAT a special tissue, which can function as an ‘energy sink’ in mammals. While a combination of high energy intake and low energy expenditure is the leading cause of overweight and obesity in modern society, activating a safe ‘energy sink’ has been proposed as a promising obesity treatment strategy. Metabolically, lipids and glucose have been viewed as the major energy substrates in BAT, while succinate, lactate, branched-chain amino acids, and other metabolites can also serve as energy substrates for thermogenesis. Since the cataplerotic and anaplerotic reactions of these metabolites interconnect with each other, BAT relies on its dynamic, flexible, and complex metabolism to support its special function. In this review, we summarize how BAT orchestrates the metabolic utilization of various nutrients to support thermogenesis and contributes to whole-body metabolic homeostasis.”
 
Questions? Please let me know (engelk@grinnell.edu).

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