Molecular Basis of White Adipose Tissue Remodeling That Precedes and Coincides With Hibernation in the Syrian Hamster, a Food-Storing Hibernator

Chayama, Yuichi; Ando, Lisa; Sato, Yuya; Shigenobu, Shuji; Anegawa, Daisuke; Fujimoto, Takayuki; Hiroki, Taii; Tsutsumi, Yutaka; Miura, Masayuki; Yamaguchi, Yoshifumi

doi:10.3389/fphys.2018.01973

Cited by 24 publications

(22 citation statements)

References 97 publications

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“…However, when exposed to cold (Barbatelli et al, 2010) and β3-adrenergic activators (Himms-Hagen et al, 2000), these beige cells acquire characteristics similar to brown adipocytes including expression of UCP1 and presence of small multilocular lipid droplets. Recruitment of beige adipocytes within WAT leads to the acquisition of thermogenic capacity in WAT, just like that of BAT (Chayama et al, 2019). Beige adipocytes can also be differentiated de novo from the dedicated white precursor cells, whenever stimuli such as β3-adrenergic activators or exposure to cold are met (Figure 1) (Harms and Seale, 2013;Rosen and Spiegelman, 2014;Merlin et al, 2016).…”

Section: Biology Of White Brown and Beige Adipose Tissuesmentioning

confidence: 99%

Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Ahmad¹,

Serpell²,

Fong³

et al. 2020

Front. Mol. Biosci.

151

112

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Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis -it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics.

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Section: Biology Of White Brown and Beige Adipose Tissuesmentioning

confidence: 99%

Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Ahmad¹,

Serpell²,

Fong³

et al. 2020

Front. Mol. Biosci.

151

112

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“…It is possible that the GD begins to increase PPAR activities and display a profile favoring lipid catabolism, possibly with preferential utilization of certain lipid types, across the entire hibernation season. If this were the case DNA-binding activity would likely show significant differences when comparing a euthermic GD during the active season, as seen in other hibernating species (Kabine et al, 2004;Chayama et al, 2018) although this comparison is out of the scope of the present study. Future studies should also address potential differences in peroxisomal lipid-metabolism in the hibernating GD given the mitochondria is less reliant on PPAR transcriptional activation, which was maintained across diets and torpor.…”

Section: Discussionmentioning

confidence: 91%

“…PPAR also regulates lipid and energy metabolism by inducing the expression of downstream genes such as fatty-acid binding protein (FABP), a key protein involved in facilitating lipid mobilization. Finally, PPAR protein and downstream gene expression is also relevant to the recruitment and activation of beige-like cells in white adipose tissue (WAT) ( Chayama et al, 2018 ). In summary, PPARs are intricately involved in a variety of essential processes owing to the importance of this regulatory network in the context of mammalian hibernation.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

et al. 2020

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Differential levels of n-6 and n-3 essential polyunsaturated fatty acids (PUFAs) are incorporated into the hibernator’s diet in the fall season preceding prolonged, multi-days bouts of torpor, known as hibernation. Peroxisome proliferator-activated receptor (PPAR) transcriptional activators bind lipids and regulate genes involved in fatty acid transport, beta-oxidation, ketogenesis, and insulin sensitivity; essential processes for survival during torpor. Thus, the DNA-binding activity of PPARα, PPARδ, PPARγ, as well as the levels of PPARγ coactivator 1α (PGC-1α) and L-fatty acid binding protein (L-FABP) were investigated in the hibernating garden dormouse (Eliomys quercinus). We found that dormice were hibernating in a similar way regardless of the n-6/n-3 PUFA diets fed to the animals during the fattening phase prior to hibernation. Further, metabolic rates and body mass loss during hibernation did not differ between dietary groups, despite marked differences in fatty acid profiles observed in white adipose tissue prior and at mid-hibernation. Overall, maintenance of PPAR DNA-binding activity was observed during torpor, and across three n-6/n-3 ratios, suggesting alternate mechanisms for the prioritization of lipid catabolism during torpor. Additionally, while no change was seen in L-FABP, significantly altered levels of PGC-1α were observed within the white adipose tissue and likely contributes to enhanced lipid metabolism when the diet favors n-6 PUFAs, i.e., high n-6/n-3 ratio, in both the torpid and euthermic state. Altogether, the maintenance of lipid metabolism during torpor makes it likely that consistent activity or levels of the investigated proteins are in aid of this metabolic profile.

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“…This approach allowed us to characterize isoforms that are changing between active and hibernation states, even when the gene itself shows no significant change in expression levels. While studies of differentially expressed genes have provided much of our current understanding in hibernation biology [15,[26][27][28][29][30][31], determining genes where functionally distinct isoforms change between seasons is the next essential biological mechanism to uncover.…”

Section: Discussionmentioning

confidence: 99%

Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos)

Tseng

et al. 2021

Preprint

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Understanding hibernation in brown bears (Ursus arctos) can provide insight into many human diseases. During hibernation, brown bears experience states of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic human diseases such as type 2 diabetes, muscle atrophy, renal and heart failure, cachexia, and obesity. The reversibility of these states from hibernation to active season allows for the identification of novel mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, we performed full-length RNA-sequencing (Iso-Seq) on three tissue types from three individuals sampled during both active and hibernation seasons. We combined the long-read data with the reference annotation for an improved transcriptome and mapped RNA-seq data from six individuals to the improved transcriptome to quantify differential isoform usage between tissues and seasons. We identified differentially expressed isoforms in all study tissues and showed that adipose has a high level of differential isoform usage with isoform switching, regardless of whether the genes were differentially expressed. Our analyses provide a comprehensive evaluation of isoform usage between active and hibernation states, revealing that differential isoform usage, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.

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Molecular Basis of White Adipose Tissue Remodeling That Precedes and Coincides With Hibernation in the Syrian Hamster, a Food-Storing Hibernator

Cited by 24 publications

References 97 publications

Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos)

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