Uncoupling Protein-1 and Related Messenger Ribonucleic Acids in Human Epicardial and Other Adipose Tissues: Epicardial Fat Functioning as Brown Fat

Sacks, Harold S.; Fain, John N.; Holman, Ben; Cheema, Paramjeet; Chary, Aron; Parks, Frank; Karas, James G.; Optican, Robert J.; Bahouth, Suleiman W.; Garrett, Edward; Wolf, Rodney Y.; Carter, Russell A.; Robbins, Todd; Wolford, David; Samaha, Joseph

doi:10.1210/mend.23.9.9997

Cited by 60 publications

(88 citation statements)

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“…S2 A-C). Human EAT is known to have brown adipose tissue character (1,13), and several BAT-specific genes, as well as pan-adipose genes, were expressed in mouse AV groove fat (Fig. S2D).…”

Section: Resultsmentioning

confidence: 99%

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Yamaguchi

Cavallero

Patterson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

116

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The hearts of many mammalian species are surrounded by an extensive layer of fat called epicardial adipose tissue (EAT). The lineage origins and determinative mechanisms of EAT development are unclear, in part because mice and other experimentally tractable model organisms are thought to not have this tissue. In this study, we show that mouse hearts have EAT, localized to a specific region in the atrial–ventricular groove. Lineage analysis indicates that this adipose tissue originates from the epicardium, a multipotent epithelium that until now is only established to normally generate cardiac fibroblasts and coronary smooth muscle cells. We show that adoption of the adipocyte fate in vivo requires activation of the peroxisome proliferator activated receptor gamma (PPARγ) pathway, and that this fate can be ectopically induced in mouse ventricular epicardium, either in embryonic or adult stages, by expression and activation of PPARγ at times of epicardium–mesenchymal transformation. Human embryonic ventricular epicardial cells natively express PPARγ, which explains the abundant presence of fat seen in human hearts at birth and throughout life.

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“…S2 A-C). Human EAT is known to have brown adipose tissue character (1,13), and several BAT-specific genes, as well as pan-adipose genes, were expressed in mouse AV groove fat (Fig. S2D).…”

Section: Resultsmentioning

confidence: 99%

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Yamaguchi

Cavallero

Patterson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

116

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“…UCP1 protein and its mRNA have recently been demonstrated in human epicardial fat (75) ; mediastinic fat of genetically-obese mice is composed of white adipocytes that are smaller than white adipocytes of subcutaneous fat (A Dover, A Frontini, S Cinti and B Walker, unpublished results). Thus, it is proposed that visceral fat is composed of smaller adipocytes because they derive from transdifferentiation of brown adipocytes.…”

Section: The Adipose Organ Renews Its Cellsmentioning

confidence: 92%

Reversible physiological transdifferentiation in the adipose organ

Cinti

2009

Proc. Nutr. Soc.

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All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.

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“…We and others have reported that UCP1 mRNA is detectable in the human mediastinal depot; however, this expression is at a much lower level relative to epicardial fat. 6,26,73 In addition, UCP1 protein does not seem to be found in abundance in human mediastinal fat depot so far.…”

Section: As a Cardiac Fat Depot Are Thermogenic Properties Exclusivementioning

confidence: 88%

“…However, a direct microcirculatory interconnection between the two has not been established so far. 23,24 Nonetheless, owing to its unique anatomic juxtaposition, numerous plausible physiological roles have been offered to epicardial fat including, but not limited to, that (1) it serves as the anatomic site for the cardiac nervous system, 25 (2) it serves to cushion the coronary arteries against pulse wave torsion, 14 (3) it serves as a heating blanket to protect the myocardium during hypothermia, 26,27 (4) it is an immunological tissue that serves to protect the myocardium and coronaries against pathogens and inflammatory activators 28 and (5) it serves to maintain fatty acid homeostasis in the coronary microcirculation. 5 In a seminal study looking at the anatomy, histology and biochemical properties of epicardial fat across a spectrum of species, epicardial fat was reported to exhibit a higher capacity for breakdown, synthesis and release of fatty acids relative to other intra-abdominal fat depots in guinea pigs.…”

Section: Physiological Relevance Of Human Epicardial Fatmentioning

confidence: 99%

“…62 However, presence of UCP1 mRNA in human epicardial fat was not demonstrated until 2009. 26 In their seminal work, Sacks et al 26 further reported that UCP1 expression associated with the age and BMI of the study participants, and also hypothesized that the thermogenic activity of epicardial brown adipocytes could serve to protect the underlying myocardium from hypothermia during cold challenge. We confirmed the presence of UCP1 mRNA in human epicardial fat in a cohort of CAD patients, and further proposed a more metabolically active role for its brown adipocytes.…”

Section: Human Epicardial Fat: a Thermogenic Tissue?mentioning

confidence: 99%

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Thermogenic potential and physiological relevance of human epicardial adipose tissue

Chechi

Richard

2015

Int J Obes Supp

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Epicardial adipose tissue is a unique fat depot around the heart that shares a close anatomic proximity and vascular supply with the myocardium and coronary arteries. Its accumulation around the heart, measured using various imaging modalities, has been associated with the onset and progression of coronary artery disease in humans. Epicardial adipose tissue is also the only fat depot around the heart that is known to express uncoupling protein 1 at both mRNA and protein levels in the detectable range. Recent advances have further indicated that human epicardial fat exhibits beige fat-like features. Here we provide an overview of the physiological and pathophysiological relevance of human epicardial fat, and further discuss whether its thermogenic properties can serve as a target for the therapeutic management of coronary heart disease in humans.

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Uncoupling Protein-1 and Related Messenger Ribonucleic Acids in Human Epicardial and Other Adipose Tissues: Epicardial Fat Functioning as Brown Fat

Cited by 60 publications

References 0 publications

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Adipogenesis and epicardial adipose tissue: A novel fate of the epicardium induced by mesenchymal transformation and PPARγ activation

Reversible physiological transdifferentiation in the adipose organ

Thermogenic potential and physiological relevance of human epicardial adipose tissue

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