Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity

Obesity and associated metabolic diseases have become a priority area of study due to the exponential increase in their prevalence and the corresponding health and economic impact. In the last decade, brown adipose tissue has become an attractive target to treat obesity. However, environmental variables such as temperature and the dynamics of energy expenditure could influence brown adipose tissue activity. Currently, most metabolic studies are carried out at a room temperature of 21 °C, which is considered a thermoneutral zone for adult humans. However, in mice this chronic cold temperature triggers an increase in their adaptive thermogenesis. In this review, we aim to cover important aspects related to the adaptation of animals to room temperature, the influence of housing and temperature on the development of metabolic phenotypes in experimental mice and their translation to human physiology. Mice studies performed in chronic cold or thermoneutral conditions allow us to better understand underlying physiological mechanisms for successful, reproducible translation into humans in the fight against obesity and metabolic diseases.

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Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

10.20944/preprints202110.0005.v1 ◽

2021 ◽

Author(s):

Rajan Singh ◽

Albert Barrios ◽

Golnaz Dirakvand ◽

Shehla Pervin

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Body Fat ◽

Metabolic Diseases ◽

Metabolic Health ◽

Increase Energy Expenditure ◽

Brown Adipose ◽

Adult Humans ◽

Treatment Of Obesity

Obesity-associated metabolic abnormalities comprise of a cluster of conditions including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. Variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. Substantially decreased BAT activity in individuals with obesity indicates a role for BAT in setting of human obesity. On the other hand, BAT mass and its prevalence has been reported to correlate with lower body mass index (BMI), decreased age and glucose levels, leading to lower incidence of cardio metabolic diseases. Increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. Deeper understanding of the role of BAT in human metabolic health and its inter-relationship with body fat distribution and deciphering proper strategies to increase energy expenditure by either increasing functional BAT mass, or inducing white adipose browning holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.

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Allicin regulates energy homeostasis through brown adipose tissue

10.1101/713305 ◽

2019 ◽

Author(s):

Chuanhai Zhang ◽

Xiaoyun He ◽

Yao Sheng ◽

Jia Xu ◽

Cui Yang ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Whole Body ◽

Brown Adipocyte ◽

Brown Adipose ◽

Promising Therapeutic Approach ◽

Treatment Of Obesity

AbstractBackground/objectives:Disorder of energy homeostasis can lead to a variety of metabolic diseases, especially obesity. Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a main bioactive ingredient in garlic, has multiple biology and pharmacological function. However, the role of Allicin, in the regulation of metabolic organ, especially the role of activation of BAT, has not been well studied. Here, we analyzed the role of Allicin in whole-body metabolism and the activation of BAT.Results:Allicin had a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in diet-introduced obesity (DIO) mice. Then we find that Allicin can strongly activate brown adipose tissue (BAT). The activation of brown adipocyte treated with Allicin was also confirmed in mouse primary brown adipocytes.Conclusion:Allicin can ameliorate obesity through activating brown adipose tissue. Our findings provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

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Unexpected evidence for active brown adipose tissue in adult humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00691.2006 ◽

2007 ◽

Vol 293 (2) ◽

pp. E444-E452 ◽

Cited By ~ 1081

Author(s):

Jan Nedergaard ◽

Tore Bengtsson ◽

Barbara Cannon

Keyword(s):

Human Physiology ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Tracer Uptake ◽

Interscapular Brown Adipose Tissue ◽

Positron Emission ◽

Brown Adipose ◽

Adult Humans ◽

Brown Adipose Tissue Activity ◽

Diet Induced Thermogenesis

The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.

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Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance

Frontiers in Physiology ◽

10.3389/fphys.2015.00004 ◽

2015 ◽

Vol 6 ◽

Cited By ~ 109

Author(s):

Anne-Laure Poher ◽

Jordi Altirriba ◽

Christelle Veyrat-Durebex ◽

FranÃ§oise Rohner-Jeanrenaud

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Brown Adipose Tissue Activity ◽

Treatment Of Obesity

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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Faculty Opinions recommendation of Identification and importance of brown adipose tissue in adult humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158818.626120 ◽

2009 ◽

Author(s):

Harold Bays

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Adult Humans

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Faculty Opinions recommendation of Identification and importance of brown adipose tissue in adult humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158818.622481 ◽

2009 ◽

Author(s):

Chantal Chenu

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Adult Humans

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Short Dietary Intervention with Olive Oil Increases Brown Adipose Tissue Activity in Lean But Not Overweight/Obese Subjects

SSRN Electronic Journal ◽

10.2139/ssrn.3675691 ◽

2020 ◽

Author(s):

Milena Monfort-Pires ◽

Muuez U-Din ◽

Guilherme A. Nogueira ◽

Juliana de Almeida-Faria ◽

Davi Sidarta-Oliveira ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Olive Oil ◽

Dietary Intervention ◽

Brown Adipose ◽

Obese Subjects ◽

Brown Adipose Tissue Activity

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Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

Scientific Reports ◽

10.1038/s41598-021-93224-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Enrique Calvo ◽

Noelia Keiran ◽

Catalina Núñez-Roa ◽

Elsa Maymó-Masip ◽

Miriam Ejarque ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Therapeutic Option ◽

Metabolic Activation ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Obesity In Mice ◽

Treatment Of Obesity ◽

Visceral Adipose

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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