The Beige Adipocyte as a Therapy for Metabolic Diseases

Lizcano, Fernando

doi:10.3390/ijms20205058

Cited by 84 publications

(69 citation statements)

References 218 publications

(241 reference statements)

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“…Expression of Retn is detected during beige adipocyte differentiation ( Fig. 4D), while at lower levels compared to white differentiation, which further suggests that Retn may be a generic marker of both white and beige adipocyte differentiation [9]. Similarly, mutant mASC-Egr1 -/cells which exhibit a robust differentiation rate, visualized by accumulation of lipid droplets in the cytoplasm (78%, Fig 4C), are characterized by higher Retn expression levels compared to wild type cells (Fig.…”

Section: Egr1 Is Necessary To Promote White and To Repress Beige Adipmentioning

confidence: 80%

Egr1loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

Bléher¹,

Meshko²,

Gergondey³

et al. 2020

Preprint

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Exercise, cold exposure and fasting lead to the differentiation of inducible-brown adipocytes, called beige adipocytes, within white adipose tissue and have beneficial effects on fat burning and metabolism, through heat production. This browning process is associated with an increased expression of the key thermogenic mitochondrial uncoupling protein 1, Ucp1. Egr1 transcription factor has been described as a regulator of white and beige differentiation programs, and Egr1 depletion is associated with a spontaneous increase of subcutaneous white adipose tissue browning, in absence of external stimulation. Here, we demonstrate that Egr1 mutant mice exhibit a restrained Ucp1 expression specifically increased in subcutaneous fat, resulting in a metabolic shift to a more brown-like, oxidative metabolism, which was not observed in other fat depots. In addition, Egr1 is necessary and sufficient to promote white and alter beige adipocyte differentiation of mouse stem cells. These results suggest that modulation of Egr1 expression could represent a promising therapeutic strategy to increase energy expenditure and to restrain obesity-associated metabolic disorders.

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Section: Egr1 Is Necessary To Promote White and To Repress Beige Adipmentioning

confidence: 80%

Egr1loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

Bléher¹,

Meshko²,

Gergondey³

et al. 2020

Preprint

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“…Based on the calculation of Ucp1 protein or mRNA abundance, it is estimated that maximumly activated beige adipocytes process about a quarter of total Ucp1-dependent thermogenic activity in mice [85]. Thus, beige adipocytes, similar to brown adipocytes, can potentially promote energy expenditure, although direct evidence is still lacking [86,87].…”

Section: Beige Adipocytes In Metabolic Diseasesmentioning

confidence: 99%

Towards a Better Understanding of Beige Adipocyte Plasticity

Paulo

Wang

2019

Cells

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Beige adipocytes are defined as Ucp1 + , multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated with certain metabolic benefits, such as reduced obesity and increased insulin sensitivity. In this review, we summarize the current knowledge regarding WAT browning, with a special focus on the beige adipocyte plasticity, collectively referring to a bidirectional transition between thermogenic active and latent states in response to environmental changes. We further exploit the utility of a unique beige adipocyte ablation system to interrogate anti-obesity effect of beige adipocytes in vivo.It has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold ( Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympathetic nerves may also contribute to beige adipocyte formation. However, the actions of sympathetic nerves, the engagement of neurotransmitters, and their receptors at the contact sites of the sympathetic nerve and receiving cell in live mice are most unknown, and functional relevance of sympathetic nerve neurotransmission in beige adipocyte plasticity, especially during the postnatal period, is not fully elucidated yet.Cells 2019, 8, 1552 2 of 16 environment, but their appearances are also negatively correlated with aging and obesity, suggesting a potential role of beige adipocytes in regulating energy homeostasis. Beige Adipocyte Formation: Different PlayersIt has been well established that activity of beige adipocytes is dominantly regulated by the sympathetic nervous system, induced by the cold or just the feeling of cold (Figure 1) [6][7][8]. Chemical denervation with 6-hydroxydopamina, prior to 3-week-old age or prior to cold exposure, impairs beige adipocyte formation, indicating the importance of sympathetic nerves during WAT browning [21]. Previous studies on anatomical positioning of sympathetic nerves in the subcutaneous inguinal white adipose tissue (iWAT), for example, by staining the tyrosine hydrolase + (Th + ) sympathetic nerves in fixed tissues [22,23], lack spatial and temporal precision [21,24,25]. Th + -sympathetic nerves and beige adipocytes are not distributed evenly across iWAT [22], suggesting that anatomic positioning of sympatheti...

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“…The prevalence of obesity presents a significant challenge for public health (1,2). The current prevention and treatments have not been effective or suitable in the long term (2,3). Obesity is characterized by increased energy intake and reduced energy expenditure.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas brown adipose tissue from the supraclavicular area are mainly composed of beige adipocytes (15,16,24,25). Aside from BAT, recruitment of beige adipocytes in white adipose tissue (WAT browning) is emerging as an interesting and promising target for therapeutic intervention in obesity and metabolic diseases (3,5,6,17,21,(26)(27)(28)(29). This is due to the fact that beige adipocytes can dissipate energy via UCP1, be recruited and differentiate from mature white adipocytes (30)(31)(32)(33) or PDGFRα + progenitors (34), smooth-muscle lineage/mural progenitors (35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, Gas proteins are coupled by β3-adrenoceptors and activate adenylate cyclase (AC) to enhance cyclic AMP (cAMP) levels followed by the protein kinase A activation and phosphorylation of p38 mitogen-activated protein kinases (p-p38MAPK). P-p38MAPK phosphorylates PPARγ cofactor-1α (PGC-1α), cAMP response element-binding protein and activating transcription factor 2 to increase UCP1 protein levels for a greater mitochondrial uncoupling capacity (3,(41)(42)(43). Multiple agents such as β3-adrenoceptor agonist and PPARγ agonists are also able to induce browning of white adipose tissue (3,5,14,26,44)}.…”

Section: Introductionmentioning

confidence: 99%

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Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Jia

Fang

et al. 2020

Preprint

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Beige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce beige adipocytes. Thus, a question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of BAT ablation by surgical denervation. The data show that beige adipocytes partly contribute to impaired glucose metabolism resulting from denervated BAT. Whereas, we found that denervated BAT were activated by cold exposure and CL316243. Thus, we further used BAT-removal animal models to abolish BAT functions completely. We found that beige adipocytes upon cold challenge or CL316243 treatments independently improved impaired glucose metabolism in BAT-removal mice. The insulin signaling was activated in BAT-removal mice upon cold exposure. Whereas, both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in BAT-removal mice with CL316243 treatments. The data show that beige adipocytes induced by cold exposure or CL316243 may have different mechanisms to improve impaired glucose metabolism. Beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissue when BAT is lacking. We provide direct evidences for the beneficial effect of beige adipocytes in glucose metabolism and energy expenditure in the absence of BAT in vivo.

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The Beige Adipocyte as a Therapy for Metabolic Diseases

Cited by 84 publications

References 218 publications

Egr1loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

Egr1loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue

Towards a Better Understanding of Beige Adipocyte Plasticity

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

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