The influence of CLA on obesity, lung function, adipokines and inflammation

Abstract

Obesity is currently widespread in the world; the epidemic and pathogenesis of the disease negatively affect several body systems including cardiovascular, endocrine and respiratory systems. Obesity influences the respiratory functions and this effect could be challenging for women, because the air way and lungs are smaller in women compared to men, as well as obesity itself exerts a negative mechanical effect on the women’s airway. Since inflammation was proposed asthe main link between obesity and lung functions, a natural supplement like conjugated linoleic acid (CLA), which has been proposed as an antiinflammatory and anti-obesity food component, could be a potential supplement that can improve the lung functions in obese women. Therefore, the aim of this thesis is to explore the effect of CLA on obesity, lung function, adipokines and inflammation. Additionally, the effect of CLA on inflammation in the current thesis was explored using novel inflammatory markers, such as adhesion molecules (CD11b and CD62L) and heat shock proteins (HSPA1A and HSPB1). Investigating the evidence about the effect of CLA supplementation on obesity in women was conducted via a systematic review with meta-analysis. The meta- analysis searched randomised control trials (RCTs) supplemented CLA mixture in form of oral capsules for less than 6 months. Two search strategies were applied, and eight eligible trials were included with 330 women. CLA significantly reduced body weight (BW; 1.2±0.26 kg, p<0.001), body mass index (BMI; 0.6 ±0.13 kg/ m², p <0.001) and total body fat (TBF; 0.76± 0.26 kg, p=0.003) when it was supplemented for short durations (6- 16 weeks). Moreover, subgroups meta-analyses were conducted which were based on obesity level, menopausal age and life style of the participants. This meta-analysis suggested a mild anti-obesity effect of CLA. However, it was not clear whether the anti-obesity effect is enough to modulate obesity-induced inflammation and lung functions. Therefore, initially a crosssectional trial was conducted to assess the direct associations between the circulating level of CLA and obesity markers, lung functions and inflammations. To the best of Knowledge, this was the first cross-sectional trial that explored these direct associations. The cross-sectional trial recruited 77 women with average age 39 years old with forced expiratory volume in one-second (FEV1) ≥70%. The level of CLA in plasma was assessed by gas chromatography; the expression of the CD markers and HSPs were assessed using flow cytometry; body composition was assessed using bioelectric impedance; and lung functions were assessed using spirometer. Interestingly, the trial revealed significant positive associations between CLA and BW (R=0.4, p<0.001), BMI (R=0.4, P<0.001) and TBF (R=0.34, P<0.001) in the overall population, and in perimenopause women. A significant inverse correlation between t10, c12-CLA and TBF was detected in overweight women (R=- 0.42, p<0.05). A significant positive association (R=0.45, P<0.04) was detected between the c9, t11-CLA and percentage peak of flow predicted (PEF %) in postmenopausal women, meanwhile t10, c12-CLA was negatively associated with peak of flow (R=-0.44, P<0.04). CLA was inversely associated with adiponectin in both obese (R=-0.55, p<0.1) and morbidly obese (R=0.48, P<0.004) women. C9, t11-CLA was positively associated with the expression of HSPA1A inside the lymphocytes in postmenopausal women (R=0.58, p=0.04). HSPB1 expression in the monocytes were associated with both c9, t11-CLA (R=0.58, p<0.05) and total CLA (R=0.71, p<0.001). The level of expression of CD11b on the pro-inflammatory monocytes (CD14++ CD16+ ) was negatively associated with CLA (R=-0.36, p<0.05). Ultimately, the study did not provide strong evidence regarding the direct relationship between CLA and obesity markers or lung functions. However, it showed a potential immunomodulatory effect of CLA on obesity-induced chronic inflammation, which subsequently could influence multiple obesity compilations. The lack of strong evidencewas primarily due to the nature of the study design (observational study). Therefore, in chapter 5 a randomised double-blind placebo control trial was conducted, for more powerful evidence based. The aim of the RCT was to look at the effect of 12-week CLA supplementation on obesity, lung function, adipokines and inflammation in obese and overweight women. The RCT recruited 56 overweight and obese women with a mean age of 42 years old, participants were randomly assigned either to receive 4.5gm/day of CLA or placebo (High Oleic Safflower oil). Participants had to attend three clinics at base line, after 6 weeks and after 12 weeks. In each clinic body composition, lung functions and inflammatory markers were assessed. The study revealed a significant 1.8% reduction in %BF in the CLA group compared to the baseline. No significant effect of CLA on the lung functions was detected, however, this study found a significant reduction in the expression of CD11b on the stimulated pro-inflammatory monocytes after 12 weeks compared to baseline in the CLA group. CLA caused a significant reduction in the expression of intracellular HSPA1A in PBMCs at week 12 compared to baseline. The results might suggest a limited anti-obesity effect of CLA, and a potential positive effect on obesity induced chronic inflammation. Ultimately, no evidence was demonstrated on the direct effect of CLA on lung functions or adipokines. The effect of CLA on adhesion molecules and HSPA1A could suggest an indirect impact on the lung function, but more research in clinically diagnosed patients with pulmonary dysfunctions could help to confirm the effect of CLA on the lung function and adipokines