Combating Obesity With Thermogenic Fat: Current Challenges and Advancements

Pan, Ruping; Xian, Zhu; Maretich, Pema; Chen, Yong

doi:10.3389/fendo.2020.00185

Cited by 50 publications

(48 citation statements)

References 120 publications

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“…It was demonstrated that scWAT exhibits a greater potential than VAT to undergo beiging, a process by which white adipocytes become brown-like and participate in energy dissipation ( 2 , 347 ). Indeed, the induction of VAT beiging has been largely regarded as an approach to curb obesity and its accompanying metabolic and cardiovascular derangements ( 348 , 349 ). Nevertheless, several visceral adipose depots including PVAT and EpiCAT intrinsically possess a beige phenotype and the implications of thermogenic induction in these particular tissues on cardiovascular functioning is not yet well-characterized, especially that the immune landscape of these tissues is less known ( 33 ).…”

Section: Immune Cell Contribution To Depot-specific Adipose Tissue Inmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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Section: Immune Cell Contribution To Depot-specific Adipose Tissue Inmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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“…In the case that beige fat exists in WAT contributing to energy consumption (12), it is promising to induce beige fat development in WAT. Notably, in recent years, studies using rodent models have shown a high plasticity of beige adipocytes regarding to its origin and regulation, the results of which have been summarized in our latest review article (71). Unlike BAT, the origin of murine beige adipocytes reported so far could be white adipocyte via transdifferentiation or distinct progenitors including PDGFRα + , mural, or MyoD + progenitors via differentiation (72)(73)(74)(75)(76)(77).…”

Section: Prospects From Rodent Experiments To a Better Metabolic Healmentioning

confidence: 99%

Metabolic Improvement via Enhancing Thermogenic Fat-Mediated Non-shivering Thermogenesis: From Rodents to Humans

et al. 2020

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Brown and beige adipose tissues play a large role in non-shivering thermogenesis (NST) in mammals, and subsequently have been studied for decades as potential therapeutic targets to treat obesity and its related metabolic diseases. However, the mechanistic regulation of brown/beige adipose tissue induction and maintenance in humans is very limited due to the ethical reasons. In fact, metabolic signaling has primarily been investigated using rodent models. A better understanding of non-shivering thermogenesis in humans is thus vital and urgent in order to treat obesity by targeting human brown adipose tissue (BAT). In this review, we summarize the anatomical and physiological differences between rodent and human BAT, current useful and mostly non-invasive methods in studying human BAT, as well as recent advancements targeting thermogenic adipocytes as a means to combat metabolic diseases in humans. Furthermore, we also discuss several novel relevant strategies of therapeutic interventions, which has been attempted in rodent experiments, and possible future investigations in humans in this field.

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“…Beiging, either through CE or β3AR agonists, has been linked to metabolic improvements, namely through increased glucose tolerance and insulin sensitivity (Baskin et al, 2018; Carpentier et al, 2018; Chen et al, 2020; Cypess et al, 2015; Darcy & Tseng, 2019; Finlin et al, 2018; Hao et al, 2019; Herz & Kiefer, 2019; Jiang et al, 2017; Loh et al, 2019; Marlatt & Ravussin, 2017; O’Mara et al, 2020; Pan et al, 2020; Peres Valgas da Silva et al, 2019; Phillips, 2019; Singh et al, 2020; Srivastava & Veech, 2019; Wang et al, 2019). Activation of the β3AR by NE on BAT initiates a cascade of secondary messengers within the cell.…”

Section: Introductionmentioning

confidence: 99%

“…Many compounds ranging from naturally occurring antioxidants to hormones, to various β3AR agonists have been investigated. The most promising results are found with β3AR agonists, although many of them are accompanied by undesirable cardiovascular side effects (Baskin et al, 2018; Carpentier et al, 2018; Chen et al, 2020; Cypess et al, 2015; Finlin et al, 2018; Hao et al, 2019; Herz & Kiefer, 2019; Loh et al, 2019; Marlatt & Ravussin, 2017; O’Mara et al, 2020; Pan et al, 2020; Pouleur et al, 2018; Singh et al, 2020). β3AR agonists and their possible use in combating metabolic disorders has previously been discussed elsewhere (Chen et al, 2020; Cypess et al, 2015; Marlatt & Ravussin, 2017; Michel et al, 2010; Schena & Caplan, 2019).…”

Section: Introductionmentioning

confidence: 99%

Mirabegron: The most promising adipose tissue beiging agent

et al. 2021

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Accumulation of white adipose tissue (WAT) underlies the obesity epidemic, leading to current therapeutic techniques that are being investigated for their ability to activate/“beige” this tissue. Adipose tissue (AT) beiging has been reported through intermittent cold exposure (CE), exercise, and β3‐Adrenergic Receptor (β3AR) agonists. But how AT beiging can help in the treatment of metabolic disorders like obesity and type 2 diabetes (T2D) remains largely unexplored. This review summarizes recent research on the use of β3AR agonist, mirabegron (Myrbetriq®), in stimulating beiging in AT. Researchers have only recently been able to determine the optimal therapeutic dose of mirabegron for inducing beiging in subcutaneous/ inguinal WAT, where the benefits of AT activation are evident without the undesired cardiovascular side effects. To determine whether the effects that mirabegron elicits are metabolically beneficial, a comparison of the undisputed findings resulting from intermittent CE‐induced beiging and the disputed findings from exercise‐induced beiging was conducted. Given the recent in vivo animal and clinical studies, the understanding of how mirabegron can be metabolically beneficial for both lean and obese individuals is more clearly understood. These studies have demonstrated that circulating adipokines, glucose metabolism, and lipid droplet (LD) size are all positively affected by mirabegron administration. Recent studies have also demonstrated that mirabegron has similar outcomes to intermittent CE and displays more direct evidence for beiging than those produced with exercise. With these current findings, mirabegron is considered the most promising and safest β3AR agonist currently available that has the potential to be used in the therapeutic treatment of metabolic disorders, and future studies into its interaction with different conditions may prove to be useful as part of a treatment plan in combination with a healthy diet and exercise.

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Combating Obesity With Thermogenic Fat: Current Challenges and Advancements

Cited by 50 publications

References 120 publications

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Metabolic Improvement via Enhancing Thermogenic Fat-Mediated Non-shivering Thermogenesis: From Rodents to Humans

Mirabegron: The most promising adipose tissue beiging agent

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