Obesity is a chronic multifactorial disease, among which are environmental, nutritional, and genetic factors, characterized by the excessive accumulation of body fat, causing damage to health [
Data from World Health Organization [
In obese subjects there is an increase in the secretion of inflammation-related proteins by adipose tissue, such as cytokines and acute phase proteins, which increase the production and circulation of other inflammatory mediators, contributing to the formation of a low-grade chronic inflammatory state [
In addition, dietary fatty acids are among the important factors of low-grade inflammation. The serum fatty acids in humans can be used as a biomarker of fatty acid intake [
A limited number of studies have verified the association between serum fatty acids composition and acute phase proteins, all of them in nonobese subjects [
Based on the above considerations, the aim of this study was to investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid and Albumin) and serum fatty acids in morbidly obese patients. Our hypothesis is that SFA will be positively correlated with positive acute phase proteins, while PUFA will demonstrate an opposite behavior.
From August to November 2011, a convenience sample of patients who were scheduled to undergo Roux-en-Y gastric bypass (
Inclusion criteria for participation were age >18 years, body mass index (BMI) >40 kg/m² or BMI >35 kg/m² with at least one comorbidity (e.g., hypertension, diabetes), and previously dietary and pharmacological treatment failure. Exclusion criteria for participation were significant intellectual limitations without adequate family support, uncontrolled psychiatric disorder, alcohol or drug dependency, current treatment with antibiotics and/or anti-inflammatory drugs, trauma, surgery or hospitalization in the last 30 days, and presence of cancer and/or genetic diseases.
Patients received interdisciplinary education about risks and changes in habits inherent in a major surgery on the digestive tract and the need for postoperative lifestyle changes. All patients underwent surgical, endocrinological, psychological, and nutritional evaluations before surgery.
This study was approved by the Ethics Committee on Research with Human Beings of this institution, which is in accordance with the Helsinki’s World Medical Declaration [
Blood samples (10 mL) were collected in the morning, before surgery procedure, after overnight fast of 8 to 12 hours. A cubital venipuncture was performed in the region of the forearm by a trained professional. Samples were collected in tubes with serum separator gel. They were left at room temperature for 30 minutes and then centrifuged at 2500 RCF (g) for 10 to 15 minutes to isolate serum. An aliquot was stored in a −80°C freezer until analysis.
Serum concentrations of CRP and ORM were determined by immunonephelometry (Siemens Dade Behring Inc., Newark, DE, USA) [
CRP/Albumin ratio proposed by Correa et al. [
Serum lipids were extracted using chloroform: methanol (2 : 1, vol : vol) according to the method described by Folch et al. [
Presurgical height and weight were obtained with participants wearing light clothing and no shoes, by a nutritionist, following standardized techniques [
The following variables were also evaluated: patient age (years), gender, smoking status, use of medication, comorbidities, length of hospital stay, and need for ventilatory support. All data were collected from medical records. With regard to smoking status, those who had smoked
Qualitative variables were described through absolute and relative frequencies, while quantitative variables were described using mean and standard deviation values or median and interquartile range values. Normality of variables was assessed by Shapiro-Wilks test. The correlation between fatty acid composition and acute phase proteins was investigated by Pearson’s (parametric variables) or Spearman’s (nonparametric variables) correlation analysis. A value of
Of the 28 patients initially recruited, six were excluded for being in treatment with anti-inflammatory/antibiotic drugs (
Table
Characteristics of morbidly obese subjects studied
Female | 18 (81.8) |
Male | 4 (18.2) |
Comorbidities | |
Hypertension | 12 (54.5) |
Diabetes mellitus | 5 (22.7) |
Hypothyroidism | 3 (13.6) |
Cholelithiasis | 1 (4.6) |
Gastritis | 1 (4.6) |
Smoking status | |
Non- | 18 (81.8) |
Former | 3 (13.6) |
Current | 1 (4.5) |
Use of medication | |
Antihypertensive drugs | 9 (40.9) |
Thiazide diuretics | 4 (18.2) |
Oral hypoglycemic agents | 3 (13.6) |
Thyroid hormones | 3 (13.6) |
Insulin | 2 (9.1) |
Proton pump inhibitors | 1 (4.6) |
Biochemical parameters of the subjects studied are shown in Table
Biochemical parameters of morbidly obese subjects studied
Parameter | Mean ± SD | Median | Min–Max |
---|---|---|---|
Albumin (g/dL) | 3.7 | 2.9–4.1 | |
CRP (mg/L) | 14.4 | 3.3–30.7 | |
ORM (mg/dL) | 108.0 | 70.7–158.0 | |
CRP/Albumin | 4.3 | 0.8–8.3 |
CRP: C-Reactive Protein; ORM: Orosomucoid; SD: standard deviation; Min: minimum; Max: maximum.
In relation to serum fatty acid composition, one sample was discarded due to problems in its analysis; therefore only 21 samples were processed. Serum proportions of fatty acids are presented in Table
Serum fatty acid composition (%) of morbidly obese subjects studied
Fatty acid | Mean ± SD | Min–Max |
---|---|---|
SFA | ||
C12:0 (lauric acid) | 8.7–22.3 | |
C14:0 (myristic acid) | 2.9–6.0 | |
C16:0 (palmitic acid) | 16.8–23.9 | |
C17:0 (margaric acid) | 0.4 (0.3–1.0)a | 0.1–1.0 |
C18:0 (stearic acid) | 2.3–6.5 | |
MUFA | ||
C16:1 n-7 (palmitoleic acid) | 14.2–25.3 | |
C18:1 n-9 (oleic acid) | 11.2–16.6 | |
n-3 PUFA | ||
C20:5 n-3 (EPA) | 1.2 (1.1–1.7)a | 0.9–1.9 |
C22:6 n-3 (DHA) | 1.9–3.1 | |
n-6 PUFA | ||
C18:2 n-6 (linoleic acid) | 3.8 (3.0–4.4)a | 2.4–4.8 |
C20:4 n-6 (AA) | 5.1–8.9 | |
n-6/n-3 | 1.5–5.0 | |
AA/EPA | 3.4–12.5 | |
PUFA/SFA | 0.2–0.5 |
AA: arachidonic acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; MUFA: monounsaturated fatty acids; PUFA: polyunsaturated fatty acids; SFA: saturated fatty acids SD: standard deviation. Min: minimum; Max: maximum.
Correlations between fatty acid composition and acute phase proteins (ORM, CRP, Albumin, and CRP/Albumin ratio) were analyzed (Table
Correlations between the relative contents of serum fatty acids and acute phase proteins in morbidly obese subjects studied
Fatty acids | ORM | CRP | Albumin | CRP/ |
---|---|---|---|---|
SFA | ||||
C12:0 (lauric acid)a | 0.07 | |||
C14:0 (myristic acid)a | ||||
C16:0 (palmitic acid)a | 0.20 | 0.10 | 0.14 | |
C17:0 (margaric acid)b | ||||
C18:0 (stearic acid)a | 0.03 | 0.11 | 0.03 | |
MUFA | ||||
C16:1 n-7 (palmitoleic acid)a | 0.24 | 0.08 | 0.18 | |
C18:1 n-9 (oleic acid)a | 0.14 | 0.23 | 0.19 | |
n-3 PUFA | ||||
C20:5 n-3 (EPA)b | ||||
C22:6 n-3 (DHA)a | 0.06 | |||
n-6 PUFA | ||||
C18:2 n-6 (linoleic acid)b | 0.19 | 0.41 | 0.39 | |
C20:4 n-6 (AA)a | 0.01 | 0.01 | ||
n-6/n-3a | 0.26 | 0.25 | ||
AA/EPAa | 0.22 | 0.23 | ||
PUFA/SFAa | 0.42 | 0.22 | 0.20 |
AA: arachidonic acid; CRP: C-reactive Protein; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; ORM: orosomucoid; MUFA: monounsaturated fatty acids; PUFA: Polyunsaturated fatty acids; SFA: saturated fatty acids.
The findings in the present study are consistent with the hypothesis that EPA (n-3 PUFA) has anti-inflammatory properties while AA (n-6 PUFA) showed an opposite behavior [
The results are consistent with other studies that found high concentrations of CRP in obese subjects [
Regarding Albumin, Schweiger et al. [
With regard to ORM, due to the slow increase in the synthesis after a stimulus and its immunomodulatory activity in situations of prolonged stress (e.g., obesity), this marker can be used as an indicator of chronic inflammation [
About the fatty acid composition in human subjects, Hodson et al. [
Nevertheless, the proportions of lauric acid and palmitoleic acid observed are unusual and require discussion. The first reason why these acids showed high proportions could be due to the fact that fatty acids were expressed as relative amounts (as proportions of the total amount of fatty acids). As a result, if the relative content of one fatty acid decreases, the relative content of other fatty acids will increase. Because PUFA showed the lowest proportion in the study (16.1%) compared to the proportions of SFA (48%) and MUFA (35.9%), it is possible that the relative content of lauric and palmitoleic acids has increased. The second reason could be due to the desaturation processes that synthesise a variety of fatty acid species. Stearoil CoA Desaturase 1 (SCD-1) is a enzyme that catalyzes the biosynthesis of MUFA from dietary or de novo synthesized SFA precursors. High SCD-1 expression is directly correlated with metabolic diseases, such as obesity [
Regarding the role of fatty acids in inflammation, controversial data are available regarding the proinflammatory role of SFA. It has been shown that lauric acid directly stimulates toll-like receptors 2/4 [
Among the fatty acids analyzed, margaric acid showed the highest correlation coefficients. Evidence is limited in obese patients regarding the associations of margaric acid with inflammatory markers. Warensjö et al. [
As expected, EPA was found to be inversely correlated with ORM and directly correlated with albumin. Differently, AA and n-6/n-3 and AA/EPA ratios were positively correlated with ORM. With regard to EPA, previous studies have described a variety of mechanisms by which EPA may influence inflammatory pathways and exert protective effects [
Similar to CRP/Albumin ratio, fatty acids were expressed as ratios. No significant relationship was found between the PUFA/SFA ratio and proteins evaluated, probably because these lipid classes include many fatty acids which have different properties. On the other hand, n-6/n-3 ratio and AA/EPA ratio were positively correlated with ORM, suggesting a pro-inflammatory role of n-6 PUFA. In fact, high serum proportions of n-6 PUFA and n-6/n-3 ratio are associated with the development of many diseases, including cardiovascular diseases, cancer, and inflammatory and autoimmune diseases [
About the study’s limitations, it should be taken into account that the analysis is limited by the cross-sectional design, which does not allow the determination of temporal relationships. Moreover, we recognize that studies with greater sample size would be appropriate, controlling for potential confounding factors such as sex, smoking status, and age.
In conclusion, our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients. Given that most significant associations have occurred with ORM, this protein may be the preferable marker to use in studies investigating relationships between serum fatty acids and low-grade inflammation. Despite these findings, further studies are also needed to confirm and explain the associations with acute phase proteins and total serum fatty acid composition, particularly in morbidly obese patients.
No conflict of interests needs to be reported. The University Hospital had no role in the analysis or interpretation of the data or in the decision to submit the report for publication.
Conception and study design: Ricardo Fernandes and Erasmo Benício Santos de Moraes Trindade. Acquisition of data: Ricardo Fernandes and Raphael Salles Granato Cunha. Analysis and interpretation of data: Ricardo Fernandes, Carolina de Quadros Camargo, Bruna Teles Soares Beserra, Elaine Hillesheim, Raphael Salles Granato Cunha and Erasmo Benício Santos de Moraes Trindade. Drafting of the manuscript: Ricardo Fernandes and Bruna Teles Soares Beserra. Statistical analysis: Ricardo Fernandes, Bruna Teles Soares Beserra and Elaine Hillesheim. Critical review of the intellectual content and final approval of the version to be published: Everson Araújo Nunes and Erasmo Benício Santos de Moraes Trindade. Material, technical and administrative support: Ricardo Fernandes, Raphael Salles Granato Cunha, Elaine Hillesheim, Danielle Cristina Tonello Pequito, Isabela Coelho, Luiz Cláudio Fernandes and Erasmo Benício Santos de Moraes Trindade. Study supervision: Ricardo Fernandes, Raphael Salles Granato Cunha, Elaine Hillesheim and Erasmo Benício Santos de Moraes Trindade.
The authors are grateful to the Multidisciplinary Integrated Residency Program in Health at the University Hospital of Federal University of Santa Catarinaby for the assistance with patients and blood sample logistic. This work was supported by the University Hospital of Federal University of Santa Catarina.