Chronic low-grade inflammation is a main pathogenic link between obesity and Type 2 Diabetes (T2D) and a putative target for treatment. While a wide array of pharmacologic agents is available to manage T2D, many patients still face perturbed glycemia and subclinical inflammation. Therefore, complementary nutraceutical strategies that target inflammation, metabolism, and resolution physiology hold promise as adjunctive options to quell the disturbed immuno-metabolic milieu observed in T2D. Omega-3 polyunsaturated fatty acids (PUFAs) and anthocyanins are two dietary components evidenced to mitigate inflammation and improve T2D risk factors, through distinct and similar targets. However, the combined use of such nutraceuticals has not yet been examined in individuals with T2D. This dissertation leveraged data from a larger randomized, double-blind, placebo-controlled trial conducted between January 2022—September 2023 investigating the use of combined supplementation (active treatment; [FOM]) of anthocyanins (600 mg/d maqui berry extract) and omega-3 PUFAs (3 g/day fish oil; 2 g/d EPA, 1 g/d DHA) for 8 weeks on cytokines and mental acuity in individuals with T2D, compared to a placebo (CON). The current study examined the effects of this supplemental strategy on markers of metabolic inflammation, oxidative stress, and cardiometabolic risk. The results indicated that a marker of sustained omega-3 dietary intake and tissue accumulation termed the Omega-3 Index was inversely associated with HbA1c (? = -8.5, 95%CI -15.1, -1.4, p = 0.022) and glucose (? = -12.4, 95%CI -22.9, -0.5, p = 0.042), after adjustment for covariates at baseline across all participants with T2D in this study. However, outcomes from linear mixed model analyses demonstrated that there were no significant differences in change from baseline between FOM and CON groups at week 8 in any of the inflammatory, oxidative stress, glycemic control, or circulating lipid markers assessed in this study. These null effects were observed despite a 93% greater increase from baseline in the Omega-3 Index observed in the FOM group compared to the CON group at week 8. Therefore, the findings do not support significant treatment effects associated with 2 months of combined marine omega-3 PUFAs and maqui berry extract on inflammatory and cardiometabolic outcomes in individuals with T2D.

Asphalt is a widely used mixture in the paving and roofing industries and its sales are expected to increase by 57% in the next eight years alone (Mandaokar, 2024). However, it is known to have highly toxic constituents such as benzo[a]pyrene (BaP) and catechol, (National Institute, 1977, Hazard Review, 2000, Neghab et al., 2015, and Rozewski et al., 2023). Lemon juice, which is an inexpensive and easily accessible natural substance that is shown to have health benefits such as increasing insulin sensitivity, aiding with weight loss, and preventing heart disease (Tejpal et al., 2020), may counteract the effects of asphalt. The question of what the biological effects of asphalt, lemon juice, and the combination of the two on adipocytes was tested via computational analysis and experiments. It was predicted that catechol and lemon juice components will show biological effects in adipocytes that could be opposing, additive, or synergistic. A computational analysis involving the docking of fourteen components of asphalt and thirty-five components of lemon juice constituents to a targetome of 7,529 proteins (Ovanessians et al., 2024) suggests that asphalt and lemon juice components have many possible protein targets. Experiments were carried out with 3T3L1 mouse adipocytes to study five different lemon extracts (crude, hexane organic and aqueous, and ether organic and aqueous), and two components of asphalt (catechol and BaP): 1) Thiazolyl Blue Tetrazolium Bromide (MTT) cell viability and toxicity assay, 2) reactive oxygen species fluorescence assay, 3) Nile red staining assay, 4) red oil o staining assay, and a 5) lipidomics analysis on the hexane and ether organic extracts of lemon juice. This study has shown that asphalt components BaP and catechol and lemon juice components combined have the following biological effects on adipocytes: 1) Of the 5 lemon extracts tested, the organic layer of the hexane extract solubilized in DMSO (LE4) decreases differentiation the most. 2) Nile red staining is inhibited by 0.1 mg/mL of LE4, 1 µM BaP, and 20 µM catechol at a similar level. 3) Cell morphology differs between LE4, BaP, and catechol. Future work will include an insulin sensitivity assay to confirm the indicative inhibitory relationship found between lemon juice and asphalt. Expanding upon the lipidomic results of the lemon juices, as well as maximizing the potential of dockings by connecting results with the experiments, may also prove to be useful in future studies.