Effects of 1α,25 Dihydroxyvitamin <i>D</i><sub>3</sub> on Pro‐inflammatory Cytokines of Palmitic Acid Treated Thp‐1 Cells

Background: The effects of iron deficiency (ID) during infancy extend beyond the hematologic compartment and include short- and long-term adverse effects on many tissues including the brain. However, sensitive biomarkers of iron-dependent brain health are lacking in humans. Objective: To determine whether serum and CSF biomarkers of ID-induced metabolic dysfunction are concordant in the pre/early anemic stage of ID prior to anemia in a nonhuman primate model of infantile IDA. Methods: Paired serum and CSF specimens were collected from iron-sufficient (IS; n = 12) and ID (n = 7) rhesus infants at 4-months (pre-anemic period) and 6-months of age (anemic). Hematological, metabolomic, and proteomic profiles were generated via HPLC/MS at both time points to discriminate serum bio markers of ID-induced brain metabolic dysfunction. Results: We identified 227 metabolites and 205 proteins in serum. Abnormalities indicating altered liver function, lipid dysregulation, and increased acute phase reactants were present in ID. In CSF, we measured 210 metabolites and 1,560 proteins with changes in ID infants indicative of metabolomic and proteomic differences indexing disrupted synaptogenesis. Systemic and CSF proteomic and metabolomic changes were present and concurrent in the pre-anemic and anemic periods. Conclusions: Multiomic serum and CSF profiling uncovered pathways disrupted by ID in both the pre-anemic and anemic stages of infantile IDA, including evidence for hepatic dysfunction and activation of acute phase response. Parallel changes observed in serum and CSF potentially provide measurable serum biomarkers of ID that reflect at-risk brain processes prior to progression to clinical anemia.

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Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Sandri

Kim

Lubach

et al. 2022

American Journal of Physiology-Regulatory, Integrative and Comp

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Hydroethanolic Extract of Lampaya Medicinalis Phil. (Verbenaceae) Decreases Proinflammatory Marker Expression in Palmitic Acid-exposed Macrophages

Ormazábal

Cifuentes

Varı̀³

et al. 2020

EMIDDT

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Background: Obesity is a major health problem associated with increased comorbidities, which are partially triggered by inflammation. Proinflammatory macrophage infiltration in adipose tissue of individuals with obesity increases chronic inflammation. Obesity is associated with elevated plasma levels of saturated fatty acids, such as palmitic acid (PA), which promotes inflammation in vivo and in vitro models. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Northern Chile to counteract inflammation of rheumatic diseases. Hydroethanolic extract of lampaya (HEL) contains spectrophotometrically defined compounds that may contribute to the observed effect on inflammation. Methods: We evaluated the phytochemical composition of HEL by high-performance liquid chromatography coupled to diode array detection (HPLC-DAD) and liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS). We assessed whether the exposure to HEL affects PA-induced expression of proinflammatory factors in THP-1 macrophages. Results: HPLC-DAD and LC-ESI-MS/MS analyses showed the presence of considerable amounts of flavonoids in HEL. The PA-induced phosphorylation of the inflammatory pathway mediators IKK and NF-κB, as well as the elevated expression and secretion of proinflammatory cytokines (IL-6, TNF-α), were reduced in cells pre-exposed to HEL. Conclusion: These findings give new insights about the effect of HEL reducing IKK/NF-κB proinflammatory pathway, likely explained by the number of flavonoid contained in the extract. More studies would be needed to define the possible role of Lampaya as a preventive approach in subjects with obesity whose circulating PA might contribute to chronic inflammation.

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Effects of 1α,25 Dihydroxyvitamin D₃ on Pro‐inflammatory Cytokines of Palmitic Acid Treated Thp‐1 Cells

Cited by 2 publications

References 79 publications

Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Hydroethanolic Extract of Lampaya Medicinalis Phil. (Verbenaceae) Decreases Proinflammatory Marker Expression in Palmitic Acid-exposed Macrophages

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Effects of 1α,25 Dihydroxyvitamin D3 on Pro‐inflammatory Cytokines of Palmitic Acid Treated Thp‐1 Cells

Cited by 2 publications

References 79 publications

Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Hydroethanolic Extract of Lampaya Medicinalis Phil. (Verbenaceae) Decreases Proinflammatory Marker Expression in Palmitic Acid-exposed Macrophages

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Effects of 1α,25 Dihydroxyvitamin D₃ on Pro‐inflammatory Cytokines of Palmitic Acid Treated Thp‐1 Cells