Adipose Snail1 Regulates Lipolysis and Lipid Partitioning by Suppressing Adipose Triacylglycerol Lipase Expression

Sun, Chengxin; Jiang, Lin; Liu, Yan; Shen, Hong; Weiss, Stephen J.; Zhou, Yifa; Rui, Liangyou

doi:10.1016/j.celrep.2016.10.070

Cited by 33 publications

(28 citation statements)

References 42 publications

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“…Organic fractions were dried in a chemical hood, resuspended in a KOH (3 M)/ethanol solution, incubated at 70°C for 1 hour, and mixed with MgCl 2 (0.75 M). Aqueous fractions were used to measure TAG levels using Free Glycerol Reagent (MilliporeSigma) (25).…”

Section: Discussionmentioning

confidence: 99%

“…Chromatin immunoprecipitation. Chromatin immunoprecipitation (ChIP) assays were described previously (25). Briefly, liver samples were treated with 1% formaldehyde for 10 minutes to cross-link DNA protein complexes.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, Snail1 emerges as a transcriptional regulator of nutrient metabolism. Adipocyte Snail1 suppresses expression of adipose triacylglycerol lipase (Atgl), thereby inhibiting lipolysis and lipid trafficking (25). Hepatocyte Snail1 suppresses hepatic Fasn expression and lipogenesis (26).…”

Section: Introductionmentioning

confidence: 99%

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Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes

Liu¹,

Lin²,

Jiang³

et al. 2020

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes

Liu¹,

Lin²,

Jiang³

et al. 2020

Journal of Clinical Investigation

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“…Unpublished observations from our laboratory also suggest that tumorigenic progression correlates with reduced ATGL activity in different types of cancer. Although no definite molecular mechanism has been revealed yet, reduced ATGL expression may associate with certain oncogenes like Snail1, to block lipolysis in malignancy [ 186 , 187 ]. Furthermore, FoxO1, an established regulator of ATGL expression, is consistently reduced in many types of cancer [ 27 , 188 , 189 ].…”

Section: What We Have Learnt From Mouse Models and Patientsmentioning

confidence: 99%

Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)

Schreiber

Xie

Schweiger

2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

129

106

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Adipose triglyceride lipase (ATGL) has been discovered 14 years ago and revised our view on intracellular triglyceride (TG) mobilization – a process termed lipolysis. ATGL initiates the hydrolysis of TGs to release fatty acids (FAs) that are crucial energy substrates, precursors for the synthesis of membrane lipids, and ligands of nuclear receptors. Thus, ATGL is a key enzyme in whole-body energy homeostasis. In this review, we give an update on how ATGL is regulated on the transcriptional and post-transcriptional level and how this affects the enzymes' activity in the context of neutral lipid catabolism. In depth, we highlight and discuss the numerous physiological functions of ATGL in lipid and energy metabolism. Over more than a decade, different genetic mouse models lacking or overexpressing ATGL in a cell- or tissue-specific manner have been generated and characterized. Moreover, pharmacological studies became available due to the development of a specific murine ATGL inhibitor (Atglistatin®). The identification of patients with mutations in the human gene encoding ATGL and their disease spectrum has underpinned the importance of ATGL in humans. Together, mouse models and human data have advanced our understanding of the physiological role of ATGL in lipid and energy metabolism in adipose and non-adipose tissues, and of the pathophysiological consequences of ATGL dysfunction in mice and men.

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“…These findings suggest that ATGL-mediated lipolysis is a regulatory node of BAT and beige fat thermogenesis and energy expenditure. We recently reported that Snail1, a transcriptional repressor, potently suppresses ATGL expression and ATGL-mediated lipolysis in adipocytes (292). ATGL activity is regulated by both positive (e.g.…”

Section: Brown and Beige Fat Thermogensismentioning

confidence: 99%

Brown and Beige Adipose Tissues in Health and Disease

Rui

2017

Comprehensive Physiology

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146

113

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Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white-to-brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells. White adipocytes can be reprogramed and transdifferentiated into beige adipocytes. Brown and beige adipocytes display many similar properties, including multilocular lipid droplets, dense mitochondria, and expression of UCP1. UCP1-mediated thermogenesis is a hallmark of brown/beige adipocytes, albeit UCP1-independent thermogenesis also occurs. Development, maintenance, and activation of BAT/beige fat are guided by genetic and epigenetic programs. Numerous transcriptional factors and coactivators act coordinately to promote BAT/beige fat thermogenesis. Epigenetic reprograming also influences expression of brown/beige adipocyte-selective genes. BAT/beige fat is regulated by neuronal, hormonal, and immune mechanisms. Hypothalamic thermal circuits define the temperature setpoint that guides BAT/beige fat activity. Metabolic hormones, paracrine/autocrine factors, and various immune cells also play a critical role in regulating BAT/beige fat functions. BAT and beige fat defend temperature homeostasis, and regulate body weight and glucose and lipid metabolism. Obesity is associated with brown/beige fat deficiency, and reactivation of brown/beige fat provides metabolic health benefits in some patients. Pharmacological activation of BAT/beige fat may hold promise for combating metabolic diseases.

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Adipose Snail1 Regulates Lipolysis and Lipid Partitioning by Suppressing Adipose Triacylglycerol Lipase Expression

Cited by 33 publications

References 42 publications

Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes

Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes

Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)

Brown and Beige Adipose Tissues in Health and Disease

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