5212Impaired function of brown adipose tissue is involved in the pathologies of pressure overload-induced heart failure

Abstract Prognosis of severe heart failure is unacceptably high, and it is our urgent task to find therapies for this critical condition. It has been reported that low body temperature predicts poor clinical outcomes in patients with heart failure, however, underlying mechanisms and pathological implications are largely unknown. Brown adipose tissue (BAT) was initially characterized as a heat generating organ, and studies suggest that BAT has crucial roles for the maintenance of systemic metabolic health. Here we show that BAT dysfunction develops in a murine thoracic aortic constriction (TAC) model, and has a causal role for promoting pathologies in failing heart. TAC operation led to a significant reduction both in intraperitoneal and subcutaneous temperature. TUNEL-positive cells significantly increased in BAT during left ventricular (LV)-pressure overload, and in-vitro studies with differentiated brown adipocytes suggested that the chronic activation of adrenergic signaling promotes apoptosis in these cells. Gain of BAT function model, generated with BAT implantation into peritoneal cavity, improved thermogenesis and ameliorated cardiac dysfunction in TAC. In contrast, genetic model of BAT dysfunction promoted cardiac dysfunction. Metabolomic analyses showed that BAT dysfunction led to an increase of oxidized choline that promoted metabolic dysfunction in the failing heart. Electron microscope study showed that oxidized choline induced mitochondrial dysfunction in vitro as well as in vivo settings. Extracellular flux analyzerindicated that oxidized choline suppresses oxidative phosphorylation in mitochondria. We found that dilated cardiomyopathy patients have lower body temperature, and confirmed by metabolomic study that both choline and oxidized choline are increased in circulation. Maintenance of BAT homeostasis and suppression of oxidized choline would become a novel therapeutic target for heart failure.

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Brown adipose tissue activation in severe heart failure

European Heart Journal ◽

10.1093/eurheartj/ehaa241 ◽

2020 ◽

Vol 41 (25) ◽

pp. 2415-2415

Author(s):

Atsuko Tahara ◽

Nobuhiro Tahara ◽

Shoko Maeda-Ogata ◽

Munehisa Bekki ◽

Yoichi Sugiyama ◽

...

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Severe Heart Failure ◽

Brown Adipose

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Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance

NMR in Biomedicine ◽

10.1002/nbm.3557 ◽

2016 ◽

Vol 29 (7) ◽

pp. 978-984 ◽

Cited By ~ 5

Author(s):

Marcello Panagia ◽

Yin-Ching Iris Chen ◽

Howard H. Chen ◽

Laura Ernande ◽

Chan Chen ◽

...

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Magnetic Resonance ◽

Brown Adipose Tissue ◽

Blood Oxygen Level Dependent ◽

Blood Oxygen ◽

Oxygen Level ◽

Blood Oxygen Level ◽

Brown Adipose

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PO-183 Effect of Treadmill Running on Brown Adipose Tissue of Heart Failure Rats Induced by Abdominal Aortic Constriction

Exercise Biochemistry Review ◽

10.14428/ebr.v1i4.12763 ◽

2018 ◽

Vol 1 (4) ◽

Author(s):

Xuefei Chen ◽

Lingjie Li ◽

Jing Zhang

Keyword(s):

Heart Failure ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Exercise Group ◽

Treadmill Running ◽

Control Group ◽

Mrna Levels ◽

Aortic Constriction ◽

Abdominal Aortic ◽

Brown Adipose

Objective To observe the effect of treadmill exercise on brown adipose tissue of heart failure rats induced by abdominal aortic constriction(AAC). Methods 210g healthy male SD rats were randomly divided into control group and AAC group，after 4 weeks abdominal aortic constriction rats were selected and randomly divided into AAC group and treadmill running group. The exercise rats underwent treadmill running at 12m/s (40 min each, for 4 weeks). Real-time PCR and immunohistochemistry were used to detect the mRNA content and protein expression of cardiac ANP, BNP, and pgc1-a, ucp-1, leptin and adiponectin of the brown adipose tissue respectively. Results The rats with abdominal aortic constriction developed significant heart failure with preserved LV ejection fraction, increased LVAW d and LVID s. Compared with the control group, the myocardium levels of ANP and BNP in AAC group were significantly up-regulated. In the operation group, the function of brown adipose was enhanced. The volume of brown adipose cells decreased, the number of lipid droplet increased. The mRNA levels of UPC-1 and PGC1-a were significantly up-regulated, and the mRNA levels of leptin and adiponectin were down-regulated. In the exercise group, the browning of brown adipose was reduced, and the mRNA levels of UPC-1 and PGC1-a were decreased. Conclusions Exercise can affect the function of brown adipose tissue in heart failure rats induced by abdominal aortic constriction.

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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