Zinc Finger Transcription Factor Zbtb16 Coordinates the Response to Energy Deficit in the Mouse Hypothalamus

Abstract

The central nervous system controls feeding behavior and energy expenditure in response to various internal and external stimuli to maintain energy balance. Here we report that the newly identified transcription factor zinc finger and BTB domain containing 16 (Zbtb16) is induced by energy deficit in the paraventricular (PVH) and arcuate (ARC) nuclei of the hypothalamus via glucocorticoid (GC) signaling. In the PVH, Zbtb16 is expressed in the anterior half of the PVH and co-expressed with many neuronal markers such as corticotropin-releasing hormone (Crh), thyrotropin-releasing hormone (Trh), oxytocin (Oxt), arginine vasopressin (Avp), and nitric oxide synthase 1 (Nos1). Knockdown (KD) of Zbtb16 in the PVH results in attenuated cold-induced thermogenesis and improved glucose tolerance without affecting food intake. In the meantime, Zbtb16 is predominantly expressed in agouti-related neuropeptide/neuropeptide Y (Agrp/Npy) neurons in the ARC and its KD in the ARC leads to reduced food intake. We further reveal that chemogenetic stimulation of PVH Zbtb16 neurons increases energy expenditure while that of ARC Zbtb16 neurons increases food intake. Taken together, we conclude that Zbtb16 is an important mediator that coordinates responses to energy deficit downstream of GCs by contributing to glycemic control through the PVH and feeding behavior regulation through the ARC, and additionally reveal its function in controlling energy expenditure during cold-evoked thermogenesis via the PVH. As a result, we hypothesize that Zbtb16 may be involved in promoting weight regain after weight loss.

Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids

“…Among the large number of downregulated DEGs, it is notable the presence of genes related with GC such as FKBP5 , a cochaperone that modulates GC receptor (GR) activity, ZBTB16 , transcriptional factor contributing to energy balance after GR activation and HPGD which encondes a dehydrogenase expressed on dexamethasone (online supplemental table 31). 29–32 Accordingly, mitochondrial metabolic process characteristic of drug metabolism, specifically GC, were significantly enriched (figure 4E and online supplemental table 33). In addition, we also found enrichment in negative regulation of the type I interferon production and the innate response as well as metabolic pathways like oxidative phosphorylation or glucose metabolic process.…”

Sex-specific transcriptomic and epitranscriptomic signatures of PTSD-like fear acquisition

“…In addition to impaired cortical morphology, these mice also show dysregulation in genes associated with myelination and neurogenesis ( Usui et al., 2021 ). Functional expression of this gene in the adult hypothalamus has been recently linked to regulation of metabolism ( Cheng et al., 2020 ). Lhx9 and Isl1 are transcription factors that also have roles in neurodevelopment ( Garcia-Calero and Puelles, 2021 ; Zhuang et al., 2013 ).…”

Bioinformatics Analysis of ZBTB16 as a Prognostic Marker for Ewing’s Sarcoma

“…Zinc-finger and BTB domain-containing 16 (ZBTB16), also known as promyelocytic leukemia zinc finger protein (PLZF), was first found in t(11;17) chromosome translocation, and fusion with retinoic acid receptor α (RARa) was identified [17]. ZBTB16 is an important mediator that regulates the expression of neuropeptides [18], ion channels [19], or various receptors [20], to influence the response to incoming signals and/or downstream neuron signals. 6 BioMed Research International ZBTB16 is expressed in various tissues and plays a variety of biological functions through the regulation of tissue-specific target genes, which is related to adipogenesis [21], myocardial remodeling [22], osteoblast differentiation [23], and obesity [24].…”