Renaissance of brown adipose tissue research: integrating the old and new

Granneman, James G.

doi:10.1038/ijosup.2015.3

Cited by 10 publications

(7 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One cohort was evaluated in cross-section analysis and the other was evaluated before and after undergoing bariatric surgery. Obesity is one of the main factors contributing to low BAT glucose uptake in humans [23,48,70,71]. Upon reduction of body mass, BAT glucose uptake increases in association with both the attenuation of insulin resistance and reduction of systemic inflammation [48,54,70].…”

Section: Discussionmentioning

confidence: 99%

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

et al. 2019

View full text Add to dashboard Cite

BackgroundInflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue.MethodsThe relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice.FindingsIL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression.InterpretationIL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function.FundSao Paulo Research Foundation grant 2013/07607-8.

show abstract

Section: Discussionmentioning

confidence: 99%

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It has been reported that thermogenic tissue is inversely related to body mass index and body fat percentage (Granneman, 2015;Peng et al, 2015;Vosselman et al, 2015).…”

Section: Role Of Adenosine In Thermogenesis During Obesitymentioning

confidence: 99%

Molecular implications of adenosine in obesity

Pardo

Villalobos-Labra

Chiarello

et al. 2017

Molecular Aspects of Medicine

View full text Add to dashboard Cite

Adenosine has broad activities in organisms due to the existence of multiple receptors, the differential adenosine concentrations necessary to activate these receptors and the presence of proteins able to synthetize, degrade or transport this nucleoside. All adenosine receptors have been reported to be involved in glucose homeostasis, inflammation, adipogenesis, insulin resistance, and thermogenesis, indicating that adenosine could participate in the process of obesity. Since adenosine seems to be associated with several effects, it is plausible that adenosine participates in the initiation and development of obesity or may function to prevent it. Thus, the purpose of this review was to explore the involvement of adenosine in adipogenesis, insulin resistance and thermogenesis, with the aim of understanding how adenosine could be used to avoid, treat or improve the metabolic state of obesity. Treatment with specific agonists and/or antagonists of adenosine receptors could reverse the obesity state, since adenosine receptors normalizes several mechanisms involved in obesity, such as lipolysis, insulin sensitivity and thermogenesis. Furthermore, obesity is a preventable state, and the specific activation of adenosine receptors could aid in the prevention of obesity. Nevertheless, for the treatment of obesity and its consequences, more studies and therapeutic strategies in addition to adenosine are necessary.

show abstract

“…In response to fasting, adipocyte lipolysis is mainly stimulated by β-adrenergic hormone norepinephrine (NE) and catalyzed sequentially by adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoacylglycerol lipase (MGL) (1,5). During chronic cold exposure, lipolytic activation by NE leads to the upregulation of thermogenic gene program in brown adipose tissue (BAT) and the appearance of brown-like (beige) adipocytes in subcutaneous white adipose tissue (WAT) (6). A promising therapeutic concept for treating obesity and its associated disorders is through expanding the beige adipocyte population and thereby enhancing whole-body energy expenditure (7).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Lipolytic Response and Energy Balance by Melanocortin 2 Receptor Accessory Protein (MRAP) in Adipocytes

et al. 2017

View full text Add to dashboard Cite

Melanocortin 2 receptor accessory protein (MRAP) is highly expressed in adrenal gland and adipose tissue. In adrenal cells, MRAP is essential for adrenocorticotropic hormone (ACTH)-induced activation of the cAMP/protein kinase A (PKA) pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid production and secretion. Although ACTH was known to stimulate PKA-dependent lipolysis, the functional involvement of MRAP in adipocyte metabolism remains incompletely defined. Herein, we found that knockdown or overexpression of MRAP in 3T3-L1 adipocytes reduced or increased ACTH-induced lipolysis, respectively. Moreover, an unbiased proteomics screen and coimmunoprecipitation analysis identified Gαs as a novel interacting partner of MRAP. An MRAP mutant disabled in Gαs association failed to augment the activation of PKA and lipolytic response to ACTH. Furthermore, compared with wild-type mice, transgenic mice (aP2-MRAP) overexpressing MRAP fat specifically exhibited increased lipolytic response to ACTH. When fed a high-fat diet (HFD), the transgenic mice displayed a significant decrease in the gain of adiposity and body weight as well as an improvement in glucose and insulin tolerance. These phenotypes were accompanied by increased adipose expression of genes for mitochondrial fatty acid oxidation and thermogenesis, and overall energy expenditure. Collectively, our data strongly suggest that MRAP plays a critical role in the regulation of ACTH-induced adipose lipolysis and whole-body energy balance.

show abstract

Renaissance of brown adipose tissue research: integrating the old and new

Cited by 10 publications

References 76 publications

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency

Molecular implications of adenosine in obesity

Regulation of Lipolytic Response and Energy Balance by Melanocortin 2 Receptor Accessory Protein (MRAP) in Adipocytes

Contact Info

Product

Resources

About