Shree, N. | Search bioRxiv

bioRxiv2024

Adipogenic differentiation and inflammatory response is orchestrated by regulating euchromatic histone methyltransferases.

Euchromatic histone methyltransferases (EHMT1/2) play a key role in adipogenesis by regulating gene expression. While the downstream gene functions of EHMTs in adipogenic differentiation have been studied, their regulation and precise individual contributions remain elusive. We discovered the existence of a regulatory mechanism, wherein EHMT1 governs the interdependent expression of itself and the master regulator PPAR during the early phase of adipogenesis. In later stages, EHMT2 levels decline along with reduction in H3K9 dimethylation. Alteration of above sequence of events alone or in the presence of saturated-fatty acids lead to precocious induction of high levels of PPAR, accelerated adipogenesis and hypertrophic adipocytes with a pro-inflammatory phenotype. Countering the decrease in EHMTs effectively abrogated the inflammatory response of the adipocytes. Accordingly, induction of obesity by a high fat diet was sufficient to downregulate H3K9me2 levels and expression of EHMTs along with enhanced IL-6 generation. Taken together, our studies reveal a critical regulatory role played by EHMTs, which coordinates adipogenesis and obesity-induced inflammation.

cell biology↗

bioRxiv2022

Multiple Postsynaptic Protein Levels Are Maintained in a Delayed Form of Compensatory, Experience-Dependent Plasticity in Adult Superior Colliculus

Visual deprivation by dark rearing in kittens and monkeys delays visual pathway development and prolongs the critical period. In contrast, receptive fields (RFs) in superior colliculus (SC) of Syrian hamsters (Mesocricetus auratus) refine normally with spontaneous activity alone, requiring only brief juvenile visual experience to maintain refined RFs in adulthood (Carrasco et al., 2005). Extending dark rearing past puberty leads to lower GAD and GABA levels due to reduced BDNF-TrkB signaling, resulting in RF re-enlargement (Carrasco et al., 2011; Mudd et al., 2019). Previous studies in kittens and monkeys have reported that dark rearing is associated with changes in both GABA ligand and GABAA receptor levels. Given the reduced GABA levels in SC of dark reared adult hamsters, we asked if dark rearing also causes changes in GABAA receptor levels. We examined expression of GABAA receptor subunits, their anchoring protein gephyrin, and the cation-chloride co-transporters KCC2 and NKCC1 in dark reared hamsters. Surprisingly, we found that dark rearing from birth until puberty had no effect on the levels of any of these postsynaptic elements, revealing a new form of maladaptive, presynaptic only inhibitory plasticity in which, rather than extending the critical period as seen in kittens and monkeys, hamster receptive fields refine normally and then lose refinement in adulthood. These results suggest that attempts to increase plasticity in adulthood for rehabilitation or recovery from injury should consider the possibility of unintended negative consequences. In addition, our results demonstrate the interesting finding that changes in neurotransmitter levels are not necessarily coordinated with changes in postsynaptic components.

neuroscience↗