A thermogenic fat-epithelium cell axis regulates intestinal disease tolerance

Man, Kevin; Bowman, Christopher J.; Braverman, Kristina N.; Escalante, Veronica; Tian, Yuan; Bisanz, Jordan E.; Ganeshan, Kirthana; Wang, Biao; Patterson, Andrew D.; Bayrer, James R.; Chawla, Ajay

doi:10.1073/pnas.2012003117

Cited by 10 publications

(11 citation statements)

References 38 publications

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Section: Controversies and Open Questionsmentioning

confidence: 99%

“…Notably, adaptive thermogenesis influences immune recruitment and composition in adipose and peripheral tissues, including the liver and gastrointestinal tract [ 145 – 147 ]. Modulating thermogenic programs, such as by increasing housing temperature to the thermoneutral zone, can alter phenotypes driven by obesity-induced inflammation, atherosclerosis, bacterial sepsis, nonalcoholic fatty liver disease, colitis and cancer [ 145 , 147 , 148 ] to those more consistently observed in human physiology. Normal vivarium conditions impose significant thermal stress on experimental animals, which can obscure experimental results and represent an additional obstacle for predictive modeling of human diseases and therapies, as humans spend most of their lives under thermoneutral conditions [ 149 ].…”

Section: Controversies and Open Questionsmentioning

confidence: 99%

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Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

2021

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Glucose is a vital source of energy for all mammals. The balance between glucose uptake, metabolism and storage determines the energy status of an individual, and perturbations in this balance can lead to metabolic diseases. The maintenance of organismal glucose metabolism is a complex process that involves multiple tissues, including adipose tissue, which is an endocrine and energy storage organ that is critical for the regulation of systemic metabolism. Adipose tissue consists of an array of different cell types, including specialized adipocytes and stromal and endothelial cells. In addition, adipose tissue harbors a wide range of immune cells that play vital roles in adipose tissue homeostasis and function. These cells contribute to the regulation of systemic metabolism by modulating the inflammatory tone of adipose tissue, which is directly linked to insulin sensitivity and signaling. Furthermore, these cells affect the control of thermogenesis. While lean adipose tissue is rich in type 2 and anti-inflammatory cytokines such as IL-10, obesity tips the balance in favor of a proinflammatory milieu, leading to the development of insulin resistance and the dysregulation of systemic metabolism. Notably, anti-inflammatory immune cells, including regulatory T cells and innate lymphocytes, protect against insulin resistance and have the characteristics of tissue-resident cells, while proinflammatory immune cells are recruited from the circulation to obese adipose tissue. Here, we review the key findings that have shaped our understanding of how immune cells regulate adipose tissue homeostasis to control organismal metabolism.

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Section: Controversies and Open Questionsmentioning

confidence: 99%

Section: Controversies and Open Questionsmentioning

confidence: 99%

Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

2021

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“…Besides, the underlying mechanism is mediated by an unexpected crosstalk between thermogenic adipocytes and intestinal epithelial cells. 339 In addition, more direct evidence has shown that the expression of UCP1 is significantly associated with better overall survival of CRC in a cohort study. 340 Furthermore, a signature consisting of six biomarkers, including UCP1, signal transducer and activator of transcription 1 (STAT1), p-cofilin, LIM domain kinase 2 (LIMK2), the Forkhead transcription factor family member 3 (FOXP3), and inducible co-stimulator (ICOS), was identified as the best combination in terms of prognostic power.…”

Section: The Developmental Origin and Anatomical Location Of Thermoge...mentioning

confidence: 99%

The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

Yin

Chen

Ruze

et al. 2022

Sig Transduct Target Ther

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The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased gradually. Most of them are listed on the table of high-risk factors for malignancy, and metabolic disorders systematically or locally contribute to cancer progression and poor prognosis of patients. Importantly, adipose tissue is fundamental to the occurrence and development of these metabolic disorders. White adipose tissue stores excessive energy, while thermogenic fat including brown and beige adipose tissue dissipates energy to generate heat. In addition to thermogenesis, beige and brown adipocytes also function as dynamic secretory cells and a metabolic sink of nutrients, like glucose, fatty acids, and amino acids. Accordingly, strategies that activate and expand thermogenic adipose tissue offer therapeutic promise to combat overweight, diabetes, and other metabolic disorders through increasing energy expenditure and enhancing glucose tolerance. With a better understanding of its origins and biological functions and the advances in imaging techniques detecting thermogenesis, the roles of thermogenic adipose tissue in tumors have been revealed gradually. On the one hand, enhanced browning of subcutaneous fatty tissue results in weight loss and cancer-associated cachexia. On the other hand, locally activated thermogenic adipocytes in the tumor microenvironment accelerate cancer progression by offering fuel sources and is likely to develop resistance to chemotherapy. Here, we enumerate current knowledge about the significant advances made in the origin and physiological functions of thermogenic fat. In addition, we discuss the multiple roles of thermogenic adipocytes in different tumors. Ultimately, we summarize imaging technologies for identifying thermogenic adipose tissue and pharmacologic agents via modulating thermogenesis in preclinical experiments and clinical trials.

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“…In addition, BAT also plays a role in regulating intestinal disease tolerance. The BAT transcriptome is dramatically altered in the early and late stages of dextran-sodium sulfate (DSS)-induced colitis in mice without inhibiting the oxygen consumption rate under hypothermic conditions, thus suggesting that BAT responds dynamically to DSS-induced colonic injury and demonstrated the existence of a signaling axis between thermogenic adipocytes and intestinal epithelial cells, which regulates disease tolerance 120 . One study performed nuclear imaging of the BAT activity coupled in subjects and followed the carotid artery anatomy and functional vascular imaging for up to five years, demonstrating that an increased BAT activity may potentially reduce the incidence of subclinical atherosclerosis and improve vascular function rather than increase the risk of CVD 121 .…”

Section: Effects Of the Thermogenic Adipose Tissue On Obesity-related...mentioning

confidence: 99%

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

Wang¹,

Qiu²,

Gan³

et al. 2022

Int. J. Biol. Sci.

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The function of the adipose tissue is influenced by complex interactions between genetics, epigenetics, and the environment, and its dysfunction can cause a variety of metabolic diseases, such as obesity or type 2 diabetes (T2D). The beige/brown adipose tissue plays a crucial role in regulating glucose and lipid metabolism by increasing energy metabolism to generate heat. The adipose tissue thermogenic program is a complex network that involves many signaling pathways regulated by coding RNAs (cRNAs) that encode transcription factor, and non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). This article discusses factors that regulate adipose tissue thermogenesis, including cRNAs and ncRNAs, and the important role of thermogenic adipose tissue in obesity-related metabolic syndrome. Several studies have shown that some cRNAs and ncRNAs can modulate the thermogenic function of adipose tissue in different ways. This article reviews the roles of cRNAs and ncRNAs in regulating thermogenesis in the beige/brown adipose tissue and the important role of the beige/brown adipose tissue in maintaining the balance of glucose and lipid metabolism in the body.

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A thermogenic fat-epithelium cell axis regulates intestinal disease tolerance

Cited by 10 publications

References 38 publications

Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

Resident and migratory adipose immune cells control systemic metabolism and thermogenesis

The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

Regulation of Adipose Thermogenesis and its Critical Role in Glucose and Lipid Metabolism

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