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

Abstract

Mammalian hibernators store fat extensively in white adipose tissues (WATs) during pre-hibernation period (Pre-HIB) to prepare for hibernation. However, the molecular mechanisms underlying the pre-hibernation remodeling of WAT have not been fully elucidated. Syrian hamsters, a food-storing hibernator, can hibernate when exposed to a winter-like short day photoperiod and cold ambient temperature (SD-Cold). Animals subjected to prolonged SD-Cold had smaller white adipocytes and beige-like cells within subcutaneous inguinal WAT (iWAT). Time-course analysis of gene expression with RNA-sequencing and quantitative PCR demonstrated that the mRNA expression of not only genes involved in lipid catabolism (lipolysis and beta-oxidation) but also lipid anabolism (lipogenesis and lipid desaturation) was simultaneously up-regulated prior to hibernation onset in the animals. The enhanced capacity of both lipid catabolism and lipid anabolism during hibernation period (HIB) is striking contrast to previous observations in fat-storing hibernators that only enhance catabolism during HIB. The mRNA expression of mTORC1 and PPAR signaling molecules increased, and pharmacological activation of PPARs indeed up-regulated lipid metabolism genes in iWAT explants from Syrian hamsters. These results suggest that the Syrian hamster rewires lipid metabolisms while preparing for hibernation to effectively utilize body fat and synthesize it from food intake during HIB.

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

“…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).…”

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

“…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.…”

“…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.…”

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

“…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.…”