Although many advanced biosensing techniques have been purposed for cytokine profiling, there are no clinically available methods that integrate high-resolution immune cell monitoring and in situ multiplexed cytokine detection together in a biomimetic tissue microenvironment. The primary challenge arises due to the lack of suitable label-free sensing techniques and difficulty for sensor integration. In this work, we demonstrated a novel integration of a localized-surface plasmon resonance (LSPR)-based biosensor with a biomimetic microfluidic ‘adipose-tissue-on-chip’ platform for an in-situ label-free, high-throughput and multiplexed cytokine secretion analysis of obese adipose tissue. Using our established adipose-tissue-on-chip platform, we were able to monitor the adipose tissue initiation, differentiation, maturation and simulate the hallmark formation of crown-like structures (CLS) during pro-inflammatory stimulation. With integrated antibody-conjugated LSPR barcode sensor arrays, our platform enables simultaneous multiplexed measurements of pro-inflammatory (IL-6, and TNF-α) and anti-inflammatory (IL-10, and IL-4) cytokines secreted by the adipocytes and macrophages. As a result, our adipose-tissue-on-chip platform is capable of identifying stage-specific cytokine secretion profiles from a complex milieu during obesity progression, highlighting its potential as a high-throughput preclinical readout for personalized obesity treatment strategies.

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Introduction Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides). Materials and methods Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus [HIV]) were enrolled in a case-control study nested within the Women’s Interagency HIV Study. Stored blood samples (1–2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata. Results Seven features differed by DM case status (all false discovery rate-adjusted q<0.05). Three flavonoids (two flavanones, one isoflavone) were respectively associated with lower odds of DM (all q<0.05), and sorbic acid was associated with greater odds of DM (all q<0.05). Conclusion Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM.

Introduction: Individuals with obesity and diabetes have increased risk for atherosclerosis; contributed by chronic systemic inflammation and elevated glycemic variability (GV). Bariatric surgery reduces circulating inflammatory markers. We aimed to determine the differences in GV and the expression of inflammatory genes from circulating white blood cells (WBC) after sleeve gastrectomy (SG) in those with and without non-insulin dependent diabetes. Methods: We conducted a prospective cohort study in subjects with obesity and type 2 diabetes (n=10) and subjects with obesity and no diabetes (n=11). Research visits occurred before SG and 6 months postoperatively. Elevated GV was defined by oral glucose tolerance test derived 1-h plasma glucose ≥155 mg/dL and elevated continuous glucose monitor derived GV index-MAGE (reference range 0-2.8 mmol/l). Bulk RNA-sequencing was performed on total WBCs, isolated neutrophils, monocytes, and lymphocytes to analyze genetic expression changes in chronic 6-month weight loss from baseline. Results: At 6 months, SG caused equivalent weight loss from baseline in both groups (22%). However, HbA1c, 1-h plasma glucose, and MAGE levels were different after SG between both groups. HbA1c decreased by 3.0±1.3% in the diabetes group (p<0.01) but was in the prediabetes range at 6 months. The mean 1-h plasma glucose levels was 228.7± 74.6 mg/dL in the diabetes group versus 137.8 ± 30.5 mg/dL in the no diabetes group, and MAGE remained elevated (4.9 ±1.5 mmol/l) only in the diabetes group at 6 months. Also, total WBC counts decreased significantly at 6 months in both groups (p<0.05). RNA sequencing analysis of these WBCs revealed that SG induced weight loss changed the expression of fewer total and WBCs subset genes in the diabetes group, and the majority of these gene expression changes (>94% of total genes) were different between both groups. Furthermore, our gene set analysis showed downregulated expression of WBC genes enriched in inflammatory pathways primarily in subjects without diabetes. Conclusion: Diabetes dampens the weight-loss induced changes to transcriptomes from WBC subsets that contribute to cardiovascular disease. Elevated GV after SG may contribute to these attenuated changes.