Biology subjects

Blanco, G. R.

Publications and source records attributed to Blanco, G. R..

3 recordsLinked to original sources

bioRxiv2025

Human brown adipose tissue demonstrates substantial 18F-fluorocholine uptake at room temperature for phosphatidylcholine synthesis

ObjectiveBrown Adipose Tissue (BAT) is composed of mitochondrial-rich, multilocular adipocytes, which dissipate energy to produce heat. Quantification of BAT mass is most commonly performed by 18F-fluorodeoxyglucose positron emission tomography (PET), which requires antecedent cold exposure. We hypothesized that 18F-fluorocholine PET could detect human BAT due to its requirement for considerable phosphatidylcholine synthesis, secondary to brown adipocytes high mitochondrial density and multiple lipid droplets. Methods1) Six healthy men with detectable 18F-fluorodeoxyglucose uptake by BAT were recruited to a randomised crossover study investigating 18F-fluorocholine uptake by BAT during warm and cold exposure. 2) 18F-fluorocholine uptake by supraclavicular adipose tissue was quantified in 76 patients who had undergone 18F-fluorocholine PET/CT scanning. 3) Choline transporter expression was quantified in human BAT and white adipose tissue (WAT), and in brown and white adipocytes. 4) Lipidomics was performed on human brown adipocytes incubated with 15N-choline to determine phospholipid synthesis. Results1) 18F-Fluorocholine uptake by BAT was substantially greater than by WAT during both warm and cold exposure. 2) 18F-Fluorocholine uptake by supraclavicular adipose tissue was higher in the colder seasons, inversely associated with body mass index, and positively associated with tissue radiodensity. 3) Expression of the choline transporter SLC44A3 was higher in human supraclavicular BAT than WAT, while SLC44A2 was expressed more highly in human brown than white adipocytes. 4) 15N-choline tracing in human brown adipocytes identified incorporation into >30 phosphatidylcholine species. Conclusions18F-fluorocholine PET may be a novel method to quantify human BAT at room temperature. HighlightsO_LI18F-Fluorocholine (FCH) PET can detect human BAT without the need for cold exposure. C_LIO_LI18F-FCH uptake by supraclavicular AT is inversely associated with body mass index. C_LIO_LIThe choline transporter SLC44A3 is more highly expressed in BAT than WAT. C_LIO_LIHuman brown adipocytes utilise choline for phosphatidylcholine synthesis. C_LI O_FIG O_LINKSMALLFIG WIDTH=168 HEIGHT=200 SRC="FIGDIR/small/671970v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11e85forg.highwire.dtl.DTLVardef@1aec87forg.highwire.dtl.DTLVardef@1ed3bf3org.highwire.dtl.DTLVardef@1fadbd1_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

physiology↗

bioRxiv2024

Noise Stress induces Cardiovascular Metabolic Shifts

Environmental stressors present in the modern world can fundamentally affect humans physiology and health. Exposure to stressors like air pollution, heat, and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke, and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately leads to activation of the renin-angiotensin-aldosterone system, increasing inflammation and oxidative stress, dramatically affecting the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here we use a murine model system of aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within days of exposing animals to aircraft noise, the heart has a reduced potential for utilising fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain for generating ATP. This is compensated by shifting energy production towards glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Our results demonstrate that within a relatively short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease. Overall, aircraft noise induces rapid, detrimental metabolic shifts in the heart, resembling patterns seen in cardiovascular diseases. These findings underscore the urgent need to comprehend the molecular consequences of environmental stressors, paving the way for targeted interventions aiming at mitigating health risks associated with chronic noise exposure in our modern, noisy environments.

systems biology↗

bioRxiv2021

Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis. HighlightsO_LITCA cycle inhibition promotes GSH synthesis and impairs de novo aspartate and proline synthesis C_LIO_LIDisruption of mitochondrial thiol redox homeostasis phenocopies TCA cycle inhibition by promoting GSH synthesis and impairing proline and aspartate synthesis C_LIO_LIAcute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis C_LIO_LITCA cycle inhibition mimics an amino acid deprivation-type response and activates ATF4 via the integrated stress response to maintain redox and amino acid homeostasis C_LI

biochemistry↗