Insights into brown adipose tissue evolution and function from non-model organisms

Jastroch, Martin; Oelkrug, Rebecca; Keipert, Susanne

doi:10.1242/jeb.169425

Cited by 47 publications

(27 citation statements)

References 90 publications

(97 reference statements)

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“…UCP1 gene was inactivated in numerous placental mammal clades (e.g. horses, whales, elephants, sea cows, hyraxes, sloths) and a number of these groups have species that are extremely cold tolerant, suggesting the existence of alternate NST mechanisms [111,112]. The whole swine family lost the UCP1 protein due to disruptions in the gene about 20 Ma [113].…”

Section: (B) Sarcolipin-based Thermogenesis In Mammals Lacking Brown mentioning

confidence: 99%

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

Bal

Periasamy

2020

Phil. Trans. R. Soc. B

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Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca 2+ -cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca 2+ transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

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Section: (B) Sarcolipin-based Thermogenesis In Mammals Lacking Brown mentioning

confidence: 99%

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

Bal

Periasamy

2020

Phil. Trans. R. Soc. B

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“…The expression of UCP1 causes a proton leak in the mitochondrial respiratory chain leading to energy dissipation as heat rather than in the form of adenosine triphosphate (ATP), therefore; it is mainly associated with energy expenditure and metabolism. 9 Other key proteins associated with brown fat phenotype include; cell-deathinducing DNA fragment factor 45-like effector A (CIDEA) and elongation of very long fatty acids 3 (ELOVL3). 10,11 The main biological function of CIDEA has not been fully defined but has been mainly implicated in lipid and energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

The expression of brown fat‐associated proteins in colorectal cancer and the relationship of uncoupling protein 1 with prognosis

Alnabulsi

Cash

et al. 2019

Intl Journal of Cancer

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Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer related death. The aberrant expression of a brown fat‐like phenotype in cancer cells has been previously implicated in tumour growth. Therefore, the expression of brown fat‐associated proteins in colorectal cancer could be associated with tumour prognosis. Monoclonal antibodies to brown fat‐associated proteins CIDEA, ELOVL3, ELOVL5, and UCP1 were developed. The antibodies were used to profile the expression of protein targets by immunohistochemistry in a discovery cohort comprising 50 normal colonic mucosa samples and 274 primary colorectal cancers and a validation cohort comprising 549 colorectal cancers. Immunostaining for UCP1 was observed in the majority of colorectal tumours while no immunostaining was observed in normal colonic mucosa (p < 0.001). The expression of UCP1 was significantly associated with better overall survival in both the discovery cohort (HR = 0.615, 95%CI = 0.416–0.909, χ2 = 6.119, p = 0.013) and the validation cohort (HR = 0.629, 95%CI = 0.480–0.825, χ2 = 11.558, p = 0.001). Furthermore, UCP1 was independently prognostic in multivariate analysis (p = 0.004). This study has identified the brown fat‐like phenotype as a novel pathway associated with survival in colorectal cancer. The expression of UCP1 was identified as a significant prognostic biomarker for colorectal cancer.

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“…Moreover, treatment with 25 µM GN up-regulated mRNA levels of FAO genes, such as peroxisome proliferator-activated receptor alpha (Pparα), peroxisome proliferator-activated receptor delta (Pparδ), carnitine palmitoyltransferase 1 (Cpt1) and carnitine palmitoyltransferase 2 (Cpt2). A recent study suggested that UCP1 in mitochondria inner membranes plays an important role in energy consumption [30,31]. We analyzed differentiated cells treated with GN using immunostaining.…”

Section: Gn Enhances Thermogenic and Fao Markers In 3t3-l1 Cellsmentioning

confidence: 99%

Gomisin N from Schisandra chinensis Ameliorates Lipid Accumulation and Induces a Brown Fat-Like Phenotype through AMP-Activated Protein Kinase in 3T3-L1 Adipocytes

Lee

Kim

et al. 2020

IJMS

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Obesity results from an imbalance between energy intake and energy expenditure, in which excess fat is stored as triglycerides (TGs) in white adipocytes. Recent studies have explored the anti-obesity effects of certain edible phytochemicals, which suppress TG accumulation and stimulate a brown adipocyte-like phenotype in white adipocytes. Gomisin N (GN) is an important bioactive component of Schisandra chinensis, a woody plant endemic to Asia. GN has antioxidant, anti-inflammatory and hepatoprotective effects in vivo and in vitro. However, the anti-obesity effects of GN in lipid metabolism and adipocyte browning have not yet been investigated. In the present study, we aimed to determine whether GN suppresses lipid accumulation and regulates energy metabolism, potentially via AMP-activated protein kinase (AMPK), in 3T3-L1 adipocytes. Our findings demonstrate that GN inhibited adipogenesis and lipogenesis in adipocyte differentiation. Also, GN not only increased the expression of thermogenic factors, including uncoupling protein 1 (UCP1), but also enhanced fatty acid oxidation (FAO) in 3T3-L1 cells. Therefore, GN may have a therapeutic benefit as a promising natural agent to combat obesity.

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Insights into brown adipose tissue evolution and function from non-model organisms

Cited by 47 publications

References 90 publications

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

The expression of brown fat‐associated proteins in colorectal cancer and the relationship of uncoupling protein 1 with prognosis

Gomisin N from Schisandra chinensis Ameliorates Lipid Accumulation and Induces a Brown Fat-Like Phenotype through AMP-Activated Protein Kinase in 3T3-L1 Adipocytes

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