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Obesity, cardiovascular disease, and role of vitamin C on inflammation: a review of facts and underlying mechanisms

Ellulu MS

Inflammopharmacology, 2017 Jun;25(3):313-328.
PMID: 28168552 DOI: 10.1007/s10787-017-0314-7

Obesity means the accumulation of excessive fat that may interfere with the maintenance of optimal state of health. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type-2 diabetes mellitus, and dyslipidemia, but there are evidences for other mediators such as chronic inflammation, oxidative stress, and thrombosis. The decreased levels of antioxidants factors and nitric oxide predispose to further cardiovascular adverse events. To reduce the risks, antioxidants can help by neutralizing the free radicals and protecting from damage by donating electrons. Having the capacity, vitamin C protects from oxidative stress, prevention of non-enzymatic glycosylation of proteins, and enhances arterial dilation through its effect on nitric oxide release. It also decreases lipid peroxidation, and alleviates inflammation. The anti-inflammatory property of vitamin C could be attributed to ability to modulate the NF-kB DNA binding activity and down-regulation in the hepatic mRNA expression for the interleukins and tumor factors.
Fulltext Gene-environment Interaction: The Causes of High Obesity Incidence

Ellulu MS, Jalambo MO

Kathmandu Univ Med J (KUMJ), 2018 2 16;15(57):91-93.
PMID: 29446373

Urbanization has provided experimental settings for testing the interactive relationship between genetic background and changes in lifestyle and dietary patterns. The concept of gene-environment interaction was described by epidemic of obesity along with urbanization. Genome-wide association has identified several genes such as melanocortin-4 receptor that associates with environmental influences of obesity. Gene environment (GxE) interaction refers to modification by an environmental factor of the effect of a genetic variant on a phenotypic trait. GxE interactions can serve to modulate the adverse effects of a risk allele, or can exacerbate the genotype-phenotype relationship and increase risk.
Fulltext Melissopalynological Study, Phenolic Compounds, and Antioxidant Properties of Heterotrigona itama Honey from Johor, Malaysia

Majid M, Ellulu MS, Abu Bakar MF

Scientifica (Cairo), 2020;2020:2529592.
PMID: 32655967 DOI: 10.1155/2020/2529592

Six honey samples produced by the stingless bee Heterotrigona itama were analyzed for their plant sources, phenolic compositions, and antioxidant activities. The honey samples were acetolyzed and identified microscopically, and the phenolic compounds were identified by using HPLC-DAD. The antioxidant activities were evaluated using three different assays (FRAP, DPPH, and ABTS) by spectrophotometry. The melissopalynological analysis showed that 26 pollen types from 14 plant families were identified in the honey. Cocos nucifera and Rhizophora mucronata presented as predominant pollen. A total of 6 phenolic acids such as catechin, chlorogenic acid, epicatechin, protocatechuic acid, p-coumaric acid, and rutin were identified. Rhizophora mucronata honey possessed the highest antioxidant activity in all assays. The result showed the influence of plant sources on the phenolic compounds and the antioxidant properties of stingless bee honey. These findings could be significant contributions for the sustainability of stingless bee industry as well as to promote Malaysian stingless bee honey worldwide.
Obesity can predict and promote systemic inflammation in healthy adults

Ellulu MS, Khaza'ai H, Rahmat A, Patimah I, Abed Y

Int J Cardiol, 2016 Jul 15;215:318-24.
PMID: 27128554 DOI: 10.1016/j.ijcard.2016.04.089

BACKGROUND: To find out the differences on biomedical data between obese and non-obese participants, and to identify risk factors associated with systemic inflammation in healthy Palestinian adults.
METHODOLOGY: A cross-sectional study involved 105 apparently healthy adults. Interview questionnaire was used to collect personal information. Participants were excluded if they suffered from acute or chronic inflammatory diseases, or continued using medicines, which might affect the biomedical results.
RESULTS: In association with increased Body Mass Index (BMI), the obese group displayed significant higher markers including: interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Obese group in association with increased waist circumference (WC) was higher significantly in inflammatory markers (IL-6, hs-CRP), lipid profile (TC) and triglyceride (TG), and blood pressure (SBP, DBP). A tertile of a feature of systemic inflammation (hs-CRP) was created, by Ordinal Logistic Regression, after adjusting for the age, gender, smoking habits, physical activity pattern, father and mother's health history; risk factors were the increased BMI [OR: 1.24] (95% CI: 1.005-1.548, P=0.050), IL-6 [OR: 3.35] (95% CI: 1.341-8.398, P=0.010), DBP [OR: 1.19] (95% CI: 1.034-1.367, P=0.015), and reduced Adiponectin [OR: 0.59] (95% CI: 0.435-0.820, P=0.001). Finally, BMI correlated with IL-6 and hs-CRP (r=0.326, P=0.005; r=0.347, P<0.001; respectively), and hs-CRP correlated with IL-6 (r=0.303, P=0.010), and inversely with Adiponectin (r=-0.342, P=0.001).
CONCLUSION: The increased level of IL-6 and reduced Adiponectin, which strongly associated with obesity, indicated that having high BMI is a useful marker in association with IL-6 and further developed systemic inflammation.
Fulltext Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial

Ellulu MS, Khaza'ai H, Patimah I, Rahmat A, Abed Y

Food Nutr Res, 2016;60:29268.
PMID: 26829184 DOI: 10.3402/fnr.v60.29268

Obesity is a degree of excess weight that predisposes people to metabolic syndromes via an inflammatory mechanism. Hypertensive and diabetic people have higher risks of developing systemic inflammation. Long chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs) can reduce the cardiovascular events and help against inflammation.
Fulltext Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial

Ellulu MS, Rahmat A, Patimah I, Khaza'ai H, Abed Y

Drug Des Devel Ther, 2015;9:3405-12.
PMID: 26170625 DOI: 10.2147/DDDT.S83144

Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.
Fulltext Obesity and inflammation: the linking mechanism and the complications

Ellulu MS, Patimah I, Khaza'ai H, Rahmat A, Abed Y

Arch Med Sci, 2017 Jun;13(4):851-863.
PMID: 28721154 DOI: 10.5114/aoms.2016.58928

Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.
Role of fish oil in human health and possible mechanism to reduce the inflammation

Ellulu MS, Khaza'ai H, Abed Y, Rahmat A, Ismail P, Ranneh Y

Inflammopharmacology, 2015 Jun;23(2-3):79-89.
PMID: 25676565 DOI: 10.1007/s10787-015-0228-1

The roles of Omega-3 FAs are inflammation antagonists, while Omega-6 FAs are precursors for inflammation. The plant form of Omega-3 FAs is the short-chain α-linolenic acid, and the marine forms are the long-chain fatty acids: docosahexaenoic acid and eicosapentaenoic acid. Omega-3 FAs have unlimited usages, and they are considered as omnipotent since they may benefit heart health, improve brain function, reduce cancer risks and improve people's moods. Omega-3 FAs also have several important biological effects on a range of cellular functions that may decrease the onset of heart diseases and reduce mortality among patients with coronary heart disease, possibly by stabilizing the heart's rhythm and by reducing blood clotting. Some review studies have described the beneficial roles of Omega-3 FAs in cardiovascular diseases (CVDs), cancer, diabetes, and other conditions, including inflammation. Studies of the effect of Omega-3 FAs gathered from studies in diseased and healthy population. CVDs including atherosclerosis, coronary heart diseases, hypertension, and metabolic syndrome were the major fields of investigation. In studies of obesity, as the central obesity increased, the level of adipocyte synthesis of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were increased and the level of anti-inflammatory adiponectin was decreased indicating a state of inflammation. The level of C reactive protein (CRP) synthesized from hepatocyte is increased by the influence of IL-6. CRP can be considered as a marker of systemic inflammation associated with increased risks of CVDs. In molecular studies, Omega-3 FAs have direct effects on reducing the inflammatory state by reducing IL-6, TNF-α, CRP and many other factors. While the appropriate dosage along with the administrative duration is not known, the scientific evidence-based recommendations for daily intake are not modified.
Atherosclerotic cardiovascular disease: a review of initiators and protective factors

Ellulu MS, Patimah I, Khaza'ai H, Rahmat A, Abed Y, Ali F

Inflammopharmacology, 2016 Feb;24(1):1-10.
PMID: 26750181 DOI: 10.1007/s10787-015-0255-y

Atherosclerotic cardiovascular disease (CVD) is a collective term comprising of a group of disorders of the heart and blood vessels. These diseases are the largest cause of morbidity and premature death worldwide. Coronary heart disease and cerebrovascular disease (stroke) are the most frequently occurring diseases. The two major initiators involved in the development of atherosclerotic CVD are vascular production of reactive oxygen species (ROS) and lipid oxidation. In atherosclerosis development, ROS is associated with rapid loss of anti-inflammatory and anti-atherogenic activities of the endothelium-derived nitric oxide (NO(·)) resulting in endothelial dysfunction. In part involving activation of the transcription factor NF-κB, ROS have been involved in signaling cascades leading to vascular pro-inflammatory and pro-thrombotic gene expression. ROS is also a potent activator of matrix metalloproteinases (MMPs), which indicate plaque destabilization and rupture. The second initiator involved in atherosclerotic CVD is the oxidation of low-density lipoproteins (LDL). Oxidation of LDL in vessel wall leads to an inflammatory cascade that activates atherogenic pathway leading to foam cell formation. The accumulation of foam cells leads to fatty streak formation, which is the earliest visible atherosclerotic lesion. In contrast, the cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and hepatic apolipoprotein E (apoE) expression can improve cardiovascular function. SERCA2a regulates the cardiac contractile function by lowering cytoplasmic calcium levels during relaxation, and affecting NO(·) action in vascular cells, while apoE is a critical ligand in the plasma clearance of triglyceride- and cholesterol-rich lipoproteins.