Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization

Liu, Pei; Huang, Shiyao; Ling, Shifeng; Xu, Shuqin; Wang, Fuhua; Zhang, Wei; Zhou, Rujiang; He, Lin; Xia, Xuan; Yao, Zhengju; Fan, Ying; Wang, Niansong; Hu, Congxia; Zhao, Xiaodong; Tucker, Haley O.; Wang, Jiqiu; Guo, Xizhi

doi:10.1038/s41467-019-12988-8

Cited by 55 publications

(42 citation statements)

References 69 publications

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“…Adipose-specific deletion of FOXP1 leads to an increase in BAT activity and WAT browning. Inversely, overexpression of FOXP1 in adipocytes impairs adaptive thermogenesis and promotes diet-induced obesity [ 36 ].…”

Section: Adipose Tissue Browningmentioning

confidence: 99%

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Kuryłowicz

Puzianowska-Kuźnicka

2020

IJMS

142

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The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.

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Section: Adipose Tissue Browningmentioning

confidence: 99%

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Kuryłowicz

Puzianowska-Kuźnicka

2020

IJMS

142

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“…In the prevailing model, cold temperatures trigger sympathetic discharge, which results in the release of noradrenaline in brown and white adipose tissue that activates β3-adrenergic receptors (β3-AR), 20 noradrenergic signaling induces the expression of thermogenic genes, which is the domain way to increase hBAT activity. CL316243 is a selective β3 agonist that could mimic cold and adrenergic simulation.…”

Section: Discussionmentioning

confidence: 99%

<p>Reduced Beige Adipogenic Potential in Subcutaneous Adipocytes Derived from Obese Chinese Individuals</p>

Li¹,

Shen

Zhang³

et al. 2020

DMSO

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Thermogenesis function has made brown/beige adipocyte an attractive target for obesity. Human brown adipose tissue activity is impaired in obesity in vivo. The present study aims to compare the differences in beige adipocyte differentiation potential of subcutaneous adipose tissue derived from normal weight and obese Chinese individuals in vitro. Methods: Adipose-derived stem cells (ADSCs) isolated from subcutaneous fat tissues of normal weight (NW) and obese (OB) groups were induced to differentiate into mature adipocyte with white adipocyte (WA)-and beige adipocyte (BA)-induction treatment. The expression of beige adipocyte marker protein UCP-1 and specific thermogenic genes was detected in differentiated adipocytes via Western blot and rt PCR, and the adipocyte mitochondrial function and lipolysis ability were also measured by oxygen consumption rate (OCR) and glycerol release rate, respectively. Results: Either with WA-induction or BA-induction, the expression of UCP-1 and beige adipocyte-specific thermogenic genes in differentiated adipocytes was higher in the NW compared to the OB group, followed by higher OCR and lipolysis ability in NW group than OB group. With BAinduction, expression of UCP-1 and thermogenic genes increased significantly, followed by the increasement in adipocytes OCR and lipolysis rate in NW group compared with WA-induction treatment, but no significant difference was observed in OB group. Conclusion: Compromised beige adipocyte differentiation plasticity was found in subcutaneous white adipose tissue derived from obese Chinese individuals, which may be due part to the downregulation of β3-adrenergic receptor expression in adipocytes. Discovery of therapeutic agents to active brown adipose tissue through specific pathways could provide a promising approach for treating obesity in the future.

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“…CDH13 gene encodes a member of the cadherin superfamily and acts as a negative regulator of axon growth during neural differentiation [38]. FOXP1 gene plays an important role in the regulation of tissue and cell type-specific gene transcription during both development and adulthood and controls adipocyte differentiation [39]. Results in GO enrichment analyses further extend to suggest that many genes are involved with growth development.…”

Section: Potential Genomic Regions and Candidate Genes Reveal The Commentioning

confidence: 90%

Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle

Zhuang

Yang

et al. 2020

Genes

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Improving the genetic process of growth traits is one of the major goals in the beef cattle industry, as it can increase meat production and reduce the cost of raising animals. Although several quantitative trait loci affecting growth traits in beef cattle have been identified, the genetic architecture of these economically important traits remains elusive. This study aims to map single nucleotide polymorphisms (SNPs) and genes associated with birth weight (BW), yearling weight (YW), average daily gain from birth to yearling (BYADG), and body weight at the age of 18 months (18MW) in a Chinese Simmental beef cattle population using a weighted, single-step, genome-wide association study (wssGWAS). Phenotypic and pedigree data from 6022 animals and genotypes from 744 animals (596,297 SNPs) were used for an association analysis. The results showed that 66 genomic windows explained 1.01-20.15% of the genetic variance for the four examined traits, together with the genes near the top SNP within each window. Furthermore, the identified genomic windows (>1%) explained 50.56%, 57.71%, 61.78%, and 37.82% of the genetic variances for BW, YW, BYADG, and 18MW, respectively. Genes with potential functions in muscle development and regulation of cell growth were highlighted as candidates for growth traits in Simmental cattle (SQOR and TBCB for BW, MYH10 for YW, RLF for BYADG, and ARHGAP31 for 18MW). Moreover, we found 40 SNPs that had not previously been identified as being associated with growth traits in cattle. These findings will further advance our understanding of the genetic basis for growth traits and will be useful for the molecular breeding of BW, YW, BYADG, and 18MW in the context of genomic selection in beef cattle.

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Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization

Cited by 55 publications

References 69 publications

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

<p>Reduced Beige Adipogenic Potential in Subcutaneous Adipocytes Derived from Obese Chinese Individuals</p>

Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle

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