Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat

Lü, Yan; Cui, Xiaona; Chen, Qi; Yang, Xiaoying; Fang, Fude; Zhang, Jun; Liu, Guoqing; Jin, Wanzhu; Chang, Yongsheng

doi:10.1016/j.celrep.2017.06.069

Cited by 108 publications

(118 citation statements)

References 52 publications

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“…PGC-1α and PRDM16, as transcription cofactors, bind to PPARγ to activate brown fat-specific gene expression [11]. Cold exposure and β-adrenergic activation are two best-characterized ways to activate brown fat [12,13]. Upon cold challenge, sympathetic nerve fibers release norepinephrine (NE) onto β-adrenergic receptors (β-ARs) on brown adipocytes and then initiate a signaling cascade in which cyclic AMP-activated protein kinase A (PKA) phosphorylates and activates the p38 mitogenactivated protein kinase (MAPK) pathway.…”

Section: Introductionmentioning

confidence: 99%

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

Fang

et al. 2019

Metabolism

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The thermogenic brown adipose tissue (BAT) has been proposed as a potential target to prevent or treat obesity and related metabolic diseases. BAT secretes adipokines to regulate the thermogenic program in an autocrine or paracrine manner. Follistatin-like 1 (FSTL1), a glycoprotein involved in adipogenesis and obesity, however, the function of FSTL1 in BAT thermogenesis and in the regulation of systemic energy homeostasis are not fully understood. Methods: Whole-body ablation Fstl1 heterozygous mice (Fstl1 +/−) and its littermates control were injected with CL316,243 to assess energy balance. A series of FSTL1 overexpression and knockdown experiments were carried out to evaluate its function in regulating thermogenic gene expression in brown adipocytes. Results: FSTL1 expression was induced upon BAT activation during cold challenge or β3-adrenergic activation. FSTL1 haploinsufficiency in mice led to reduced thermogenic gene expression, impaired BAT recruitment, and decreased heat production. FSTL1 cell-autonomously promoted the β3-adrenergic signaling, which was required to upregulate PPARγ and UCP1 in brown adipocytes. Furthermore, only glycosylated FSTL1 could be secreted from brown adipocytes to induce the β3-adrenergic activation. Conclusions: Our results suggest FSTL1 as a novel stimulator of the β-adrenergic signaling and BAT thermogenesis.

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Section: Introductionmentioning

confidence: 99%

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

Fang

et al. 2019

Metabolism

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“…The membrane was blocked at room temperature in 5% BSA for 2 h, and the membrane was incubated with primary antibodies (UCP1 primary antibody, rabbit 1:1000, Abcam, Cambridge, UK; PGC1α primary antibody, rabbit, 1:1000, Abcam, Cambridge, UK; ACTIN primary antibody, mouse, 1:1000, Cambridge, UK; TUBULIN primary antibody, rabbit, 1:1000, Cambridge, UK) overnight at 4 °C. The following day, the membrane was washed in TBST three times, 10 min each, and the membrane was incubated with secondary antibodies for 2 h. The protein bands were visualized by chemiluminescence (Bio-Rad, Hercules, CA, USA) [34]. …”

Section: Methodsmentioning

confidence: 99%

Trans-Ferulic Acid-4-β-Glucoside Alleviates Cold-Induced Oxidative Stress and Promotes Cold Tolerance

Xue

Liu

et al. 2018

IJMS

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Trans-ferulic acid-4-β-glucoside (C16H20O9, TFA-4β-G) is a monomer extracted from the Chinese medicine called radix aconiti carmichaeli (Fuzi). To date, research on this substance is lacking. Here, we found that trans-ferulic acid-4-β-glucoside effectively promoted cold acclimatization in mice via increased heat production and alleviation of oxidative stress in a cold environment. Thus, our work indicates that ferulic acid-4-β-glucoside is a potential therapeutic candidate for prevention and treatment of cold stress injury.

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“…▶table 1 illustrates the effect of BAT activation via cold exposure and exercise on UCP1 and PGC-1α. In rodents, exposure to 4 °C increased UCP1 mRNA consistently after 3-24 h [17,[27][28][29][72][73][74][75][76][77][78][79][80], an effect that is maintained for up to 7 days [47,72,[81][82][83]. Chronic cold exposure for 4-5 weeks resulted in a new acclimation state characterized by elevated UCP1 content, demonstrating that cold exposure robustly increases UCP1 content in rodent BAT [47,84].…”

Section: Activation Of Ucp1mentioning

confidence: 99%

Is Exercise a Match for Cold Exposure? Common Molecular Framework for Adipose Tissue Browning

2020

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Exercise is commonly utilized for weight loss, yet research has focused less on specific modifications to adipose tissue metabolism. White adipose tissue (WAT) is the storage form of fat, whereas brown adipose tissue (BAT) is a thermogenic tissue whose uncoupling increases energy expenditure. The most established BAT activator is cold exposure, which also transforms WAT into “beige cells” that express uncoupling protein 1 (UCP1). Preliminary evidence in rodents suggests exercise elicits similar effects. The purpose of this review is to parallel and examine differences between exercise and cold exposure on BAT activation and beige induction. Like cold exposure, exercise stimulates the sympathetic nervous system and activates molecular pathways responsible for BAT/beige activation, including upregulation of BAT activation markers (UCP1, proliferator-activated receptor-gamma coactivator-1α) and stimulation of endocrine activators (fibroblast growth factor-21, irisin, and natriuretic peptides). Further, certain BAT activators are altered exclusively by exercise (interleukin-6, lactate). Markers of BAT activation increase from both cold exposure and exercise, whereas effects in WAT are compartment-specific. Stimulation of endocrine activators depends on numerous factors, including stimulus intensity and duration. Evidence of these analogous, albeit not mirrored, mechanisms is demonstrated by increases in adipose activity in rodents, while effects remain challenging to quantify in humans.

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Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat

Cited by 108 publications

References 52 publications

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

Trans-Ferulic Acid-4-β-Glucoside Alleviates Cold-Induced Oxidative Stress and Promotes Cold Tolerance

Is Exercise a Match for Cold Exposure? Common Molecular Framework for Adipose Tissue Browning

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