Fatty Acids, Amphiregulin Production, and Lung Function in a Cohort of Midwestern Veterans

Corrine Hanson; Jana Ponce; Mia Isaak; Art Heires; Tara Nordgren; Chris Wichman; Jeremy D Furtado; Tricia LeVan; Debra Romberger

doi:10.3389/fresc.2022.773835

Fatty Acids, Amphiregulin Production, and Lung Function in a Cohort of Midwestern Veterans

Front Rehabil Sci. 2022 Mar 4:3:773835. doi: 10.3389/fresc.2022.773835. eCollection 2022.

Authors

Corrine Hanson¹, Jana Ponce¹, Mia Isaak¹, Art Heires^{2

3}, Tara Nordgren⁴, Chris Wichman⁵, Jeremy D Furtado⁶, Tricia LeVan^{2

3}, Debra Romberger^{2

3}

Affiliations

¹ Department of Medical Sciences, Division of Medical Nutrition, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, United States.
² Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
³ VA Nebraska Western Iowa Healthcare System, Omaha, NE, United States.
⁴ Colorado State University, Fort Collins, CO, United States.
⁵ Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States.
⁶ Harvard T. H. Chan School of Public Health, Boston, MA, United States.

Abstract

Rationale: The relationship between many fatty acids and respiratory outcomes remains unclear, especially with regard to mechanistic actions. Altered regulation of the process of lung repair is a key feature of chronic lung disease and may impact the potential for pulmonary rehabilitation, but underlying mechanisms of lung repair following injury or inflammation are not well-studied. The epidermal growth factor receptor agonist amphiregulin (AREG) has been demonstrated to promote lung repair following occupational dust exposure in animals. Studies suggest the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) may enhance the production of AREG. The objective of this study was to determine the relationship between fatty acids and lung function in a population of veterans and determine if fatty acid status is associated with concentrations of AREG.

Materials and methods: Data were collected from a cross-sectional study of veterans within the Nebraska-Western Iowa Health Care System. Whole blood assays were performed to quantify AREG concentrations via a commercially available ELISA kit. Fatty acids from plasma samples from the same patients were measured using gas-liquid chromatography. Intakes of fatty acids were quantified with a validated food frequency questionnaire. Linear regression models were used to determine whether plasma fatty acids or intakes of fatty acids predicted lung function or AREG concentrations. A p < 0.05 was considered statistically significant.

Results: Ninety participants were included in this analysis. In fully adjusted models, plasma fatty acids were associated with AREG production, including the PUFA eicosapentaenoic acid (EPA) (β = 0.33, p = 0.03) and the monounsaturated fatty acid octadecenoic acid: (β = -0.56, p = 0.02). The omega-3 PUFA docosapentaenoic acid (DPA) was positively associated with lung function (β = 0.28, p = 0.01; β = 26.5, p = 0.05 for FEV₁/FVC ratio and FEV₁ % predicted, respectively), as were the omega-6 PUFAs eicosadienoic acid (β = 1.13, p < 0.001; β = 91.2, p = 0.005 for FEV₁/FVC ratio and FEV₁ % predicted, respectively) and docosadienoic acid (β = 0.29, p = 0.01 for FEV₁/FVC ratio). Plasma monounsaturated and saturated fatty acids were inversely associated with lung function.

Conclusion: Opposing anti- and pro-inflammatory properties of different fatty acids may be associated with lung function in this population, in part by regulating AREG induction.

Keywords: DHA; EPA; amphiregulin; fatty acid (composition); geriatric; lung function; omega 3 fatty acid; pulmonary rehabilitation.