In vivo emergence of beige-like fat in chickens as physiological adaptation to cold environments

Sotome, Rina; Hirasawa, Akira; Kikusato, Motoi; Amo, Taku; Furukawa, Kyohei; Kuriyagawa, Anna; Watanabe, Kouichi; Collin, Anne; Shirakawa, Hitoshi; Hirakawa, Ryota; Tanitaka, Yuta; Takahashi, Hideki; Wu, Guoyao; Nochi, Tomonori; Shimmura, Tsuyoshi; Warden, Craig H; Toyomizu, Masaaki

doi:10.1007/s00726-021-02953-5

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…Furthermore, avian uncoupling protein (avUCP), which shares high homology with human UCP3, has been suggested as an important protein for thermogenesis in avian species such as chicken, hummingbirds, and king penguins [64,65]. In another study on chicken, the avUCP was activated by cold exposure and ADRB stimulation using isoproterenol, contributing to the induction of beige-like adipose tissue [66,67]. These results suggested that the functional role of UCP3 may vary based on the presence of BAT or UCP1 among different animals, and UCP3 may have the ability of browning.…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Kim,

Yazawa,

Koide

et al. 2024

Biology

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Adipose tissue plays an important role in regulating body temperature and metabolism, with white adipocytes serving as storage units for energy. Recent research focused on the browning of white adipocytes (beige adipocytes), causing thermogenesis and lipolysis. The process of browning is linked to the activation of uncoupling protein (UCP) expression, which can be mediated by the β3 adrenergic receptor pathway. Transcriptional factors, such as peroxisome proliferator activated receptor γ (PPARγ) and PPARγ coactivator 1 alpha, play vital roles in cell fate determination for fat cells. Beige adipocytes have metabolic therapeutic potential to combat diseases such as obesity, diabetes mellitus, and dyslipidemia, owing to their significant impact on metabolic functions. However, the molecular mechanisms that cause the induction of browning are unclear. Therefore, research using animal models and primary culture is essential to provide an understanding of browning for further application in human metabolic studies. Pigs have physiological similarities to humans; hence, they are valuable models for research on adipose tissue. This study demonstrates the browning potential of pig white adipocytes through primary culture experiments. The results show that upregulation of UCP3 gene expression and fragmentation of lipid droplets into smaller particles occur due to isoproterenol stimulation, which activates beta-adrenergic receptor signaling. Furthermore, PPARγ and PGC-1α were found to activate the UCP3 promoter region, similar to that of UCP1. These findings suggest that pigs undergo metabolic changes that induce browning in white adipocytes, providing a promising approach for metabolic research with potential implications for human health. This study offers valuable insights into the mechanism of adipocyte browning using pig primary culture that can enhance our understanding of human metabolism, leading to cures for commonly occurring diseases.

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Section: Discussionmentioning

confidence: 99%

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Kim,

Yazawa,

Koide

et al. 2024

Biology

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“…In the case that the observed stimulatory effect of diclazuril occurred in treated poultry, this could result in elevated tissue energy expenditure and metabolism by increasing TH-dependent gene expression in the muscle and liver. While it has been thought that BAT-dependent thermogenesis is absent in the chicken, this has been recently questioned by demonstrating the emergence of beige-like fat as a physiological adaptation to cold [ 49 ]. This induction of BAT TH signaling by diclazuril could contribute to non-shivering thermogenesis and energy loss also in the chicken, but further studies are required to directly prove this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A and Diclazuril Evoke Tissue-Specific Changes of Thyroid Hormone Signaling in Male Thyroid Hormone Action Indicator Mice

Sinkó

Rada

Kollár

et al. 2022

IJMS

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Thyroid hormone (TH) signaling is a prerequisite of normal tissue function. Environmental pollutants with the potential to disrupt endocrine functions represent an emerging threat to human health and agricultural production. We used our Thyroid Hormone Action Indicator (THAI) mouse model to study the effects of tetrabromobisphenol A (TBBPA; 150 mg/bwkg/day orally for 6 days) and diclazuril (10.0 mg/bwkg/day orally for 5 days), a known and a potential hormone disruptor, respectively, on local TH economy. Tissue-specific changes of TH action were assessed in 90-day-old THAI mice by measuring the expression of a TH-responsive luciferase reporter in tissue samples and by in vivo imaging (14-day-long treatment accompanied with imaging on day 7, 14 and 21 from the first day of treatment) in live THAI mice. This was followed by promoter assays to elucidate the mechanism of the observed effects. TBBPA and diclazuril impacted TH action differently and tissue-specifically. TBBPA disrupted TH signaling in the bone and small intestine and impaired the global TH economy by decreasing the circulating free T4 levels. In the promoter assays, TBBPA showed a direct stimulatory effect on the hdio3 promoter, indicating a potential mechanism for silencing TH action. In contrast, diclazuril acted as a stimulator of TH action in the liver, skeletal muscle and brown adipose tissue without affecting the Hypothalamo-Pituitary-Thyroid axis. Our data demonstrate distinct and tissue-specific effects of TBBPA and diclazuril on local TH action and prove that the THAI mouse is a novel mammalian model to identify TH disruptors and their tissue-specific effects.

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“…Luijten et al [ 49 ] reported that chronic GC-induced obesity develops independently of UCP1. Recently, Sotome et al [ 50 ] demonstrated that abdominal fat exhibits increased lipolysis probably without increased thermogenesis in white leghorn chickens. Therefore, even though chronic CORT exposure increased browning marker gene expression, white adipose browning could not influence the visceral fat deposition.…”

Section: Discussionmentioning

confidence: 99%

m6A-Mediated PPARA Translational Suppression Contributes to Corticosterone-Induced Visceral Fat Deposition in Chickens

Zhou

Zhang

Liu

et al. 2022

IJMS

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Excess fat deposition in broilers leads to great economic losses and is harmful to consumers’ health. Chronic stress in the life cycle of chickens could be an important trigger. However, the underlying mechanisms are still unclear. In this study, 30-day-old chickens were subcutaneously injected with 2 mg/kg corticosterone (CORT) twice a day for 14 days to simulate long-term stress. It was shown that chronic CORT exposure significantly increased plasma triglyceride concentrations and enlarged the adipocyte sizes in chickens. Meanwhile, chronic CORT administration significantly enlarged the adipocyte sizes, increased the protein contents of FASN and decreased HSL, ATGL, Beclin1 and PPARA protein levels. Moreover, global m6A methylations were significantly reduced and accompanied by downregulated METTL3 and YTHDF2 protein expression by CORT treatment. Interestingly, the significant differences of site-specific m6A demethylation were observed in exon7 of PPARA mRNA. Additionally, a mutation of the m6A site in the PPARA gene fused GFP and revealed that demethylated RRACH in PPARA CDS impaired protein translation in vitro. In conclusion, these results indicated that m6A-mediated PPARA translational suppression contributes to CORT-induced visceral fat deposition in chickens, which may provide a new target for the treatment of Cushing’s syndrome.

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In vivo emergence of beige-like fat in chickens as physiological adaptation to cold environments

Cited by 9 publications

References 58 publications

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway

Tetrabromobisphenol A and Diclazuril Evoke Tissue-Specific Changes of Thyroid Hormone Signaling in Male Thyroid Hormone Action Indicator Mice

m6A-Mediated PPARA Translational Suppression Contributes to Corticosterone-Induced Visceral Fat Deposition in Chickens

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