Michael Snyder, Postdoctoral Faculty Sponsor
Multi-omics microsampling for the profiling of lifestyle-associated changes in health.
Nature biomedical engineering
Current healthcare practices are reactive and use limited physiological and clinical information, often collected months or years apart. Moreover, the discovery and profiling of blood biomarkers in clinical and research settings are constrained by geographical barriers, the cost and inconvenience of in-clinic venepuncture, low sampling frequency and the low depth of molecular measurements. Here we describe a strategy for the frequent capture and analysis of thousands of metabolites, lipids, cytokines and proteins in 10 μl of blood alongside physiological information from wearable sensors. We show the advantages of such frequent and dense multi-omics microsampling in two applications: the assessment of the reactions to a complex mixture of dietary interventions, to discover individualized inflammatory and metabolic responses; and deep individualized profiling, to reveal large-scale molecular fluctuations as well as thousands of molecular relationships associated with intra-day physiological variations (in heart rate, for example) and with the levels of clinical biomarkers (specifically, glucose and cortisol) and of physical activity. Combining wearables and multi-omics microsampling for frequent and scalable omics may facilitate dynamic health profiling and biomarker discovery.
View details for DOI 10.1038/s41551-022-00999-8
View details for PubMedID 36658343
Toxicity and Metabolomic Impact of Cobalt, Chromium, and Nickel Exposure on HepaRG Hepatocytes.
Chemical research in toxicology
Cobalt, chromium, and nickel are used in orthopedic prostheses. They can be released, accumulate in many organs, and be toxic. The aim of this study is to evaluate the cytotoxicity of these metals on human hepatocytes and to improve our knowledge of their cellular toxicity mechanisms by metabolomic analysis. HepaRG cells were incubated for 48 h with increasing concentrations of metals to determine their IC50. Then, a nontargeted metabolomic study using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was done at IC50 and at a lower concentration (100 nM), near to those found in the blood and liver of patients with prostheses. IC50 were defined at 940, 2, and 1380 muM for Co, Cr, and Ni, respectively. In vitro, Cr appears to be much more toxic than Co and Ni. Metabolomic analysis revealed the disruption of metabolic pathways from the low concentration of 100 nM, in particular tryptophan metabolism and lipid metabolism illustrated by an increase in phenylacetylglycine, a marker of phospholipidosis, for all three metals. They also appear to be responsible for oxidative stress. Dysregulation of these pathways impacts hepatocyte metabolism and may result in hepatotoxicity. Further investigations on accessible biological matrices should be conducted to correlate our in vitro results with the clinical data of prostheses-bearing patients.
View details for DOI 10.1021/acs.chemrestox.1c00429
View details for PubMedID 35442019
Cadmium acute exposure induces metabolic and transcriptomic perturbations in human mature adipocytes.
Obesity is considered as a major public health concern with strong economic and social burdens. Exposure to pollutants such as heavy metals can contribute to the development of obesity and its associated metabolic disorders, including type 2 diabetes and cardiovascular diseases. Adipose tissue is an endocrine and paracrine organ that plays a key role in the development of these diseases and is one of the main target of heavy metal accumulation. In this study, we determined by inductively coupled plasma mass spectrometry cadmium concentrations in human subcutaneous and visceral adipose tissues, ranging between 2.5nM and 2.5M. We found a positive correlation between cadmium levels and age, sex and smoking status and a negative correlation between Cd and body mass index. Based on cadmium adipose tissue concentrations found in humans, we investigated the effects of cadmium exposure, at concentrations between 1nM and 10M, on adipose-derived human mesenchymal stem cells differentiated into mature adipocytes in vitro. Transcriptomic analysis highlighted that such exposure altered the expression of genes involved in trace element homeostasis and heavy metal detoxification, such as Solute Carrier Family transporters and metallothioneins. This effect correlated with zinc level alteration in cells and cellular media. Interestingly, dysregulation of zinc homeostasis and transporters has been particularly associated with the development of obesity and type 2 diabetes. Moreover, we found that cadmium exposure induces the pro-inflammatory state of the adipocytes by enhancing the expression of genes such as IL-6, IL-1B and CCL2, cytokines also induced in obesity. Finally, cadmium modulates various adipocyte functions such as the insulin response signaling pathway and lipid homeostasis. Collectively, our data identified some of the cellular mechanisms by which cadmium alters adipocyte functions, thus highlighting new facets of its potential contribution to the progression of metabolic disorders.
View details for DOI 10.1016/j.tox.2022.153153
View details for PubMedID 35301059