Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity

Baranwal, Aparna; Schade, Kimberly N.

doi:10.2174/1573399812666160517115450

Cited by 32 publications

(40 citation statements)

References 154 publications

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“…However more recently, by using routine 18 F-glucose imaging for the detection of neoplasms, considerable depots of BAT were discovered above the clavicular bones and near the cervical and thoracic vertebrae in at least some adult humans 51 . This discovery has stimulated renewed interest in harnessing this tissue for the fight against obesity 52 . How BAT, which is present in considerable amounts in newborns, can be preserved through adolescence and adulthood, and how it can be activated to burn energy is of great interest.…”

Section: Neural Controls Of Energy Expenditurementioning

confidence: 99%

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

2017

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The brain plays a key role in the controls of energy intake and expenditure and many genes associated with obesity are expressed in the central nervous system. Technological and conceptual advances in both basic and clinical neurosciences have expanded the traditional view of homeostatic regulation of body weight by mainly the hypothalamus to include hedonic controls of appetite by cortical and subcortical brain areas processing external sensory information, reward, cognition, and executive functions. Thus, hedonic controls interact with homeostatic controls to regulate body weight in a flexible and adaptive manner that takes environmental conditions into account. This new conceptual framework has several important implications for the treatment of obesity. Because much of this interactive neural processing is outside awareness, cognitive restraint in a world of plenty is made difficult and prevention and treatment of obesity should be more rationally directed to the complex and often redundant mechanisms underlying this interaction.

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Section: Neural Controls Of Energy Expenditurementioning

confidence: 99%

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

2017

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“…121 Attempts to activate BAT through adenoceptor agonists proved to be effective in mice but did not yield similar results in clinical trials because of lack of bioavailability. 122 Whether the direct use of BMPs and their inhibitors can be more effective in reducing body fat remains to be seen.…”

Section: Unanswered Questions and Perspectivesmentioning

confidence: 99%

“…However, the exact volume of human BAT remains unknown, and there are conflicting reports on whether or not BAT activation, even at its full capacity, would be enough to significantly affect energy expenditure . Attempts to activate BAT through adenoceptor agonists proved to be effective in mice but did not yield similar results in clinical trials because of lack of bioavailability . Whether the direct use of BMPs and their inhibitors can be more effective in reducing body fat remains to be seen.…”

Section: Introductionmentioning

confidence: 99%

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Blázquez‐Medela

Jumabay

Boström³

2019

Obesity Reviews

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Summary The bone morphogenetic proteins (BMPs) belong to the same superfamily as related to transforming growth factor β (TGFβ), growth and differentiation factors (GDFs), and activins. They were initially described as inducers of bone formation but are now known to be involved in morphogenetic activities and cell differentiation throughout the body, including the development of adipose tissue and adipogenic differentiation. BMP4 and BMP7 are the most studied BMPs in adipose tissue, with major roles in white adipogenesis and brown adipogenesis, respectively, but other BMPs such as BMP2, BMP6, and BMP8b as well as some inhibitors and modulators have been shown to also affect adipogenesis. It has become ever more important to understand adipose regulation, including the BMP pathways, in light of the strong links between obesity and metabolic and cardiovascular disease. In this review, we summarize the available information on BMP signaling in adipose tissue using preferentially articles that have appeared in the last decade, which together demonstrate the importance of BMP signaling in adipose biology.

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“…Consequently, the therapy of obesity by means of BAT and brite fat not only requires strategies to activate it but also to increase its abundance. Several natural compounds and drugs are associated with the activation and recruitment of BAT in mice and humans (9,10). Among these are metabolites of omega-6 and omega-3 polyunsaturated fatty acids (PUFA).…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

et al. 2020

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Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning in vivo is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity.

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Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity

Cited by 32 publications

References 154 publications

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

Blaming the Brain for Obesity: Integration of Hedonic and Homeostatic Mechanisms

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue

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