Biology subjects

Cortez, B. N.

Publications and source records attributed to Cortez, B. N..

3 recordsLinked to original sources

bioRxiv2023

Adrenergic Reprogramming of Preexisting Adipogenic Trajectories Steer Naive Mural Cells Toward Beige Differentiation

In adult white adipose tissue, cold or {beta}3-adrenoceptor activation promotes the appearance of thermogenic beige adipocytes. Our comprehensive single-cell analysis revealed that these cells arise through the reprogramming of existing adipogenic trajectories, rather than from a single precursor. These trajectories predominantly arise from SM22-expressing vascular mural progenitor cells. Central in this transition is the activation of Adrb3 in mature adipocytes, leading to subsequent upregulation of Adrb1 in primed progenitors. Under thermoneutral conditions, synergistic activation of both Adrb3 and Adrb1 recapitulates the pattern of cold-induced SM22+ cell recruitment. Lipolysis-derived eicosanoids, specifically docosahexaenoic acid (DHA) and arachidonic acid (AA) prime these processes and in vitro, were sufficient to recapitulate progenitor cells priming. Collectively, our findings provide a robust model for cold-induced beige adipogenesis, emphasizing a profound relationship between mature adipocytes and mural cells during cold acclimation, and revealing the metabolic potential of this unique cellular reservoir.

cell biology↗

bioRxiv2022

DNA methylation supports accelerated biological age in Type 2 Diabetes which can be reversed with pharmacological treatments: Retrospective Cohort Study

BackgroundBiological age (BA) closely depicts age-related changes at a cellular level. Type 2 Diabetes mellitus (T2D) accelerates BA when calculated using clinical biomarkers. However, there is a large spread of individual BA within these groups and it is unclear what clinical biomarkers correlate with different speeds of aging and whether pharmacological treatment of diabetes alter BA. We hypothesized that accelerated BA would be seen at the DNA methylation (DNAm) level, the gold standard to determine BA, and biomarkers and treatments would correlate the rate of BA in T2D. MethodsPublicly available DNAm samples were obtained from the GEO NCBI database and the NHANES 2017-2018 and ACCORD Cohorts were used for our analysis. We used the DNA Methylation Phenotypic Age algorithm and the Klemera and Doubal (KDM) methods to calculate BA with DNA methylation and clinical biomarkers, respectively. ResultsDNAm showed increased BA in whole blood and pancreatic islets in T2D in aging-related pathways, such as DNA damage and inflammation. Using the NHANES and ACCORD Trial cohorts, we found that avoidance of fried and fatty foods, and vigorous activity correlated with decreased BA in T2D. Cardiovascular, glycemic, and inflammatory biomarkers associated with the rate of aging in DM. Intensive blood pressure and T2D treatment associated with a greater deceleration in the speed of aging as compared to the standard. ConclusionsOverall, we show that certain tissues age faster in people with T2D and this strongly associates with blood glucose control, inflammation and cardiovascular health. Effective treatment of the disease can decelerate aging and decrease BA suggesting the latter as a novel and integrated index to evaluate and follow people with T2D. FundingThis study was supported by Institutional Startup Funds to C.A.M. (Joslin Diabetes Center) and NIH grants P30 DK036836 Joslin Diabetes Research Center (Bioinformatic Core).

physiology↗

bioRxiv2020

Single cell atlas of beige remodeling of white adipose tissue reveals a myeloid to lymphoid shift during cold exposure compared to beta 3 adrenergic stimulation

White adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its related metabolic complications. Within the cell mixture that constitutes the stromal vascular fraction (SVF), WAT beiging is initiated through expansion and differentiation of adipocytes progenitor cells, however, the extent of the SVF cellular changes is still poorly understood. Additionally, direct beta 3 adrenergic receptor (Adrb3) stimulation has been extensively used to mimic physiological cold- induced beiging, yet it is still unknown whether Adrb3 activation induces the same WAT remodeling as cold exposure. Here, by using single cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling within white adipose tissue. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold exposure induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis, showed that Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cells recruitment. These findings provide new insight into the cellular dynamics during WAT beige remodeling and could ultimately lead to novel strategies to identify translationally-relevant drug targets to counteract obesity and T2D.

cell biology↗