New Powers of Brown Fat: Fighting the Metabolic Syndrome

Nedergaard, Jan; Bengtsson, Tore; Cannon, Barbara

doi:10.1016/j.cmet.2011.02.009

Cited by 170 publications

(160 citation statements)

References 10 publications

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“…BAT thermogenesis is underpinned by high energy consumption, suggesting that defective BAT may contribute causally to obesity and that BAT activation may have therapeutic potential for weight control [8,9]. These possibilities have been substantiated by rodent studies demonstrating that BAT contributes ≥50% of total glucose and triacylglycerol clearance after gavage feeding [10,11] and ∼50% of adrenergically stimulated energy consumption above basal levels [12] in wild-type mice housed at room temperature. Furthermore, after prolonged cold exposure, BAT, via adaptive thermogenesis, is directly responsible for more than doubling whole-body energy expenditure [13].…”

Section: Introductionmentioning

confidence: 70%

Ephedrine activates brown adipose tissue in lean but not obese humans

et al. 2012

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Aims/hypothesis Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. Methods We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22±1 kg/m 2 ) and nine obese (BMI 36±1 kg/m 2 ) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [ 18 F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging.

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Section: Introductionmentioning

confidence: 70%

Ephedrine activates brown adipose tissue in lean but not obese humans

et al. 2012

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“…Browning is of remarkable pathophysiological interest, because it could be harnessed to tackle obesity and metabolic syndrome (45,46,47,48). Indeed, ectopic UCP1 expression (49) and expression in white adipocytes of key molecules involved in brown adipocyte differentiation, such as Prdm16 (50), induce obesity resistance and ameliorate insulin sensitivity.…”

Section: White-brown Plasticitymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

Giordano

Smorlesi

Frontini

et al. 2014

European Journal of Endocrinology

224

177

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In mammals, adipocytes are lipid-laden cells making up the parenchyma of the multi-depot adipose organ. White adipocytes store lipids for release as free fatty acids during fasting periods; brown adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the pink adipocyte, has recently been characterised in mouse subcutaneous fat depots during pregnancy and lactation. Pink adipocytes are mammary gland alveolar epithelial cells whose role is to produce and secrete milk. Emerging evidence suggests that they derive from the transdifferentiation of subcutaneous white adipocytes. The functional response of the adipose organ to a range of metabolic and environmental challenges highlights its extraordinary plasticity. Cold exposure induces an increase in the 'brown' component of the organ to meet the increased thermal demand; in states of positive energy balance, the 'white' component expands to store excess nutrients; finally, the 'pink' component develops in subcutaneous depots during pregnancy to ensure litter feeding. At the cell level, plasticity is provided not only by stem cell proliferation and differentiation but also, distinctively, by direct transdifferentiation of fully differentiated adipocytes by the stimuli that induce genetic expression reprogramming and through it a change in phenotype and, consequently function. A greater understanding of adipocyte transdifferentiation mechanisms would have the potential to shed light on their biology as well as inspire novel therapeutic strategies against metabolic syndrome (browning) and breast cancer (pinking).

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“…Classical BAT, found most prominently in the interscapular region of rodents, is critical for TG clearance, glucose disposal, and for nonshivering thermogenesis. BAT has an enormous effect on metabolic rate; small alterations in BAT activity can impact multiple metabolic variables ( 207 ). Thus, understanding the effect of BAT is essential for complete metabolic phenotyping in mice.…”

Section: In Vitro Adipogenesis Assaysmentioning

confidence: 99%

Improved methodologies for the study of adipose biology: insights gained and opportunities ahead

Wang

Scherer

Gupta

2014

Journal of Lipid Research

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greater caution must be taken in interpreting studies of adipogenesis and adipocyte metabolism.In this review, we offer a consolidated view of the wideranging approaches that can be taken to study adipose biology and discuss important considerations and pitfalls associated with each method. We divide the discussion into three sections; the fi rst section describes model systems, ways to understand where and when molecules of interest may play a role in the adipose lineage, and recent insights gained from these approaches. The second and third sections provide guidelines for the study of adipocyte biology in vivo and in cellular systems, respectively. Along the way, we highlight improved genetic and cellular models that can aid researchers interested in studying the role of their favorite protein in the adipose tissue and discuss the insights gained from each approach. IS MY FAVORITE GENE EXPRESSED IN THE ADIPOSE LINEAGE? WHERE DO I LOOK?The establishment and maintenance of adipocytes in principle involves key regulatory steps ( 3 ). First, multipotent progenitor cells must commit to the adipocyte lineage, a process referred to as preadipose cell determination. Next, in response to appropriate spatial and temporal cues, committed preadipose cells undergo adipocyte differentiation, a morphological and biochemical transition into mature adipocytes. Finally, mechanisms must exist that function to maintain the differentiated state of the mature adipocyte (adipocyte maintenance). This includes factors critical for regulating the functional properties of Abstract Adipocyte differentiation and function have become areas of intense focus in the fi eld of energy metabolism; however, understanding the role of specifi c genes in the establishment and maintenance of fat cell function can be challenging and complex. In this review, we offer practical guidelines for the study of adipocyte development and function. We discuss improved cellular and genetic systems for the study of adipose biology and highlight recent insights gained from these new approaches. -Wang, Q. A., P. E. Scherer, and R. K. Gupta. Improved methodologies for the study of adipose biology: insights gained and opportunities ahead. J. Lipid Res. 2014. 55: 605-624. Supplementary key words energy metabolism • adipogenesis • obesitySince the 1970s, fat cell differentiation of immortalized fi broblast cell lines has been an extensively studied model of cellular differentiation ( 1 ). The ability to study this process in a tissue culture dish has allowed cellular biologists and biochemists to explore general mechanisms of cell fate determination and cellular differentiation, and to isolate novel regulatory proteins and signaling cascades that initiate these processes . However, it is now clear that adipocytes represent critical regulators of nearly all aspects of energy balance. Adipose tissues exhibit high plasticity with a tremendous capacity for expansion and contraction in response to the energy demands of an organism. The alarming rise in obesity and obesity-l...

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New Powers of Brown Fat: Fighting the Metabolic Syndrome

Cited by 170 publications

References 10 publications

Ephedrine activates brown adipose tissue in lean but not obese humans

Ephedrine activates brown adipose tissue in lean but not obese humans

MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ

Improved methodologies for the study of adipose biology: insights gained and opportunities ahead

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