How Does Fat Transition from White to Beige?

Reitman, Marc L.

doi:10.1016/j.cmet.2017.06.011

Cited by 28 publications

(22 citation statements)

References 10 publications

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“…Interestingly, similar to Tsc1 ‐deficient myeloid cells, deletion of endoplasmic reticulum stress sensor inositol requiring enzyme 1α (IRE1α) promotes M2 macrophage polarization, increases BAT thermogenic activity, and protects mice from diet‐induced obesity . Possible mechanisms by which M2 macrophages promote BAT thermogenic activation may involve modulation of tissue sympathetic innervation and adrenergic signaling, local secretion of pro‐thermogenic factors, and reduction of pro‐inflammatory M1 macrophages and TLR4 signaling, which has been shown to reduce BAT mitochondrial respiration, UCP1 content, and sympathetic innervation …”

Section: Discussionmentioning

confidence: 99%

“…[33] Interestingly, similar to Tsc1-deficient myeloid cells, deletion of endoplasmic reticulum stress sensor inositol requiring enzyme 1α (IRE1α) promotes M2 macrophage polarization, increases BAT thermogenic activity, and protects mice from diet-induced obesity. [34] Possible mechanisms by which M2 macrophages promote BAT thermogenic activation may involve modulation of tissue sympathetic innervation and adrenergic signaling, [33] local secretion of pro-thermogenic factors, [35] and reduction of proinflammatory M1 macrophages and TLR4 signaling, which has been shown to reduce BAT mitochondrial respiration, UCP1 content, and sympathetic innervation. [36,37] Phenocopying the enhanced M2 macrophage polarization found in vivo and further supporting the notion that elevated adipose tissue M2 macrophages content is a cause and not consequence of the protection against obesity, Tsc1-deficient BMDM displayed in vitro, in an mTORC1-dependent manner, enhanced autonomous (in the absence of stimulus) and stimulated (IL-4+IL-13) polarization to a M2 profile.…”

Section: Discussionmentioning

confidence: 99%

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Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet‐Induced Obesity

Paschoal

Belchior

Amano

et al. 2018

Molecular Nutrition Food Res

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet‐Induced Obesity

Paschoal

Belchior

Amano

et al. 2018

Molecular Nutrition Food Res

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“…At least 25 different compounds can activate BAT in mice [65]. The mouse appears to be sensitive and possibly overly permissive as a screen.…”

Section: Drug Activation Of Human Batmentioning

confidence: 99%

Of mice and men – environmental temperature, body temperature, and treatment of obesity

Reitman

2018

FEBS Letters

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104

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Mice are widely used for exploring obesity physiology and treatment. However, thermal biology is different between small and large mammals. In this Review, we discuss how the effect of environmental temperature must be understood to ensure applicability of mouse experiments to human obesity. At ambient environmental temperature (~ 22 °C), over one-third of energy expenditure in mice is devoted to maintaining core body temperature, largely by brown adipose tissue. To conserve this energy, mice can enter a regulated hypothermia, while humans do not. Since humans expend little or no energy specifically to keep warm, mice studied at thermoneutrality (~ 30 °C) may be a better model for human energy homeostasis. Studies indicate that environmental temperature also affects the efficacy of drugs that increase energy expenditure. In mice, dinitrophenol, a protonophore, and CL316243, a β3-adrenergic agonist, both increase metabolic rate at thermoneutrality, but only CL316243 increases it at 22 °C. Furthermore, mice housed at thermoneutrality may become more obese than mice at 22 °C. Thus, we discuss the importance of studying mice at both thermoneutrality and at lower temperatures in obesity research.

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“…Brown fat dissipates large amounts of chemical energy as heat, and its activation exerts anti-obesity and anti-diabetic effects [2]. Numerous reports demonstrated an inverse relationship between brown fat activity and adiposity even in adult human [1, 7–11].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1β on White Adipocyte Browning

et al. 2017

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Adipose tissue expansion is accompanied by infiltration and accumulation of pro-inflammatory macrophages, which links obesity to pathologic conditions such as type 2 diabetes. However, little is known regarding the role of pro-inflammatory adipose tissue remodeling in the thermogenic activation of brown/beige fat. Here, we investigated the effect of pattern recognition receptors (PRR) activation in macrophages, especially the toll-like receptor 4 (TLR4) and Nod-like receptor 3 (NLRP3), on white adipocyte browning. We report that TLR4 activation by lipopolysaccharide repressed white adipocyte browning in response to β3-adrenergic receptor activation and caused ROS production and mitochondrial dysfunction, while genetic deletion of TLR4 protected mitochondrial function and thermogenesis. In addition, activation of NLRP3 inflammasome in macrophages attenuated UCP1 induction and mitochondrial respiration in cultures of primary adipocytes, while the absence of NLRP3 protected UCP1 in adipocytes. The effect of NLRP3 inflammasome activation on browning was mediated by IL-1β signaling, as blocking IL-1 receptor in adipocytes protected thermogenesis. We also report that IL-1β interferes with thermogenesis via oxidative stress stimulation and mitochondrial dysfunction as we observed a statistically significant increase in ROS production, decrease in SOD enzyme activity, and increase in mitochondrial depolarization in adipocytes treated with IL-1β. Collectively, we demonstrated that inflammatory response to obesity, such as TLR4 and NLRP3 inflammasome activation as well as IL-1β secretion, attenuates β3-adrenoreceptor-induced beige adipocyte formation via oxidative stress and mitochondrial dysfunction. Our findings provide insights into targeting innate inflammatory system for enhancement of the adaptive thermogenesis against obesity.

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How Does Fat Transition from White to Beige?

Cited by 28 publications

References 10 publications

Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet‐Induced Obesity

Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet‐Induced Obesity

Of mice and men – environmental temperature, body temperature, and treatment of obesity

Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1β on White Adipocyte Browning

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