Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria

Fedorenko, Andriy; Lishko, Polina V.; Kirichok, Yuriy

doi:10.1016/j.cell.2012.09.010

Cited by 820 publications

(825 citation statements)

References 46 publications

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“…73). Recently, Fedorenko et al 74 discovered that long-chain fatty acids generated in the inner mitochondrial membrane by phospholipase A2 (Pla2) bind Ucp1 directly and are required for proton transport (Fig. 3).…”

Section: Sympathetic Nerve Control Of Brown and Beige Fatmentioning

confidence: 99%

Brown and beige fat: development, function and therapeutic potential

Harms

Seale

2013

Nat Med

1,999

2,054

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Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.npg

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Section: Sympathetic Nerve Control Of Brown and Beige Fatmentioning

confidence: 99%

Brown and beige fat: development, function and therapeutic potential

Harms

Seale

2013

Nat Med

1,999

2,054

View full text Add to dashboard Cite

show abstract

“…39 In contrast to general chemical uncouplers, such as 2,4-dinitrophenol, UCP1-mediated themogenesis is a highly regulated process that requires physiological stimulation of the cAMP signaling pathway. 40 Hence, modulating UCP1 expression and activity in adipose tissue may constitute a safer avenue to increase energy expenditure.…”

Section: Small-molecule Screening To Identify Pharmacological Activatmentioning

confidence: 99%

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Kajimura

2015

Int J Obes Supp

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Obesity develops from a chronic energy imbalance in which energy intake exceeds energy expenditure. As brown adipose tissue (BAT) dissipates energy and produces heat, increasing energy expenditure via BAT thermogenesis may constitute a novel therapeutic intervention for the treatment of obesity and obesity-related diseases. Studies over the past few years have identified key regulatory molecules of brown and beige adipocyte biogenesis, including a dominant transcriptional co-regulator PRDM16 (PR domain containing 16) and its co-factors, which allows for engineering functional BAT by genetic approaches. A next step toward the goal of promoting BAT thermogenesis by pharmacological approaches necessitates a better understanding of the enzymatic components and signaling pathways for brown and beige adipocyte development. This review covers recent advances regarding this topic, with a special emphasis on the PRDM16 transcriptional pathway.

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“…20 Apart from being the main substrate for the thermogenesis, the released free fatty acids also serve as direct activators of UCP1. 21 Upon activation by cold, the perfusion of BAT also increases markedly, 22,23 serving to supply the tissue with oxygen for thermogenesis and to spread the generated heat to the rest of the body.…”

Section: Bat and Thermogenic Adipocytesmentioning

confidence: 99%

Brown adipose tissue and bone

Lidell

Enerbäck

2015

Int J Obes Supp

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ME Lidell and S EnerbäckBrown adipose tissue (BAT) is capable of transforming chemically stored energy, in the form of triglycerides, into heat. Recent studies have shown that metabolically active BAT is present in a large proportion of adult humans, where its activity correlates with a favorable metabolic status. Hence, the tissue is now regarded as an interesting target for therapies against obesity and associated diseases such as type 2 diabetes, the hypothesis being that an induction of BAT would be beneficial for these disease states. Apart from the association between BAT activity and a healthier metabolic status, later studies have also shown a positive correlation between BAT volume and both bone cross-sectional area and bone mineral density, suggesting that BAT might stimulate bone anabolism. The aim of this review is to give the reader a brief overview of the BAT research field and to summarize and discuss recent findings regarding BAT being a potential player in bone metabolism.

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Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria

Cited by 820 publications

References 46 publications

Brown and beige fat: development, function and therapeutic potential

Brown and beige fat: development, function and therapeutic potential

Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway

Brown adipose tissue and bone

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