European Heart Journal Advance Access originally published online on October 25, 2007
European Heart Journal 2007 28(23):2953-2954; doi:10.1093/eurheartj/ehm472
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Obesity and its relationship to coronary heart disease
UND Life Sciences 13800 Fairhill Road, #321 Shaker Heights, OH 44120, USA
Tel: +1 216 231 5548 Fax: 928-833-0316 E-mail address: undurti{at}hotmail.com
There is reasonable evidence to believe that obesity and its associated conditions such as hypertension, dyslipidemia, type 2 diabetes mellitus, atherosclerosis, and coronary heart disease are low-grade systemic inflammatory conditions.1,2 Although adipose tissue distribution is dependent on genetic, environmental, and hormonal factors, there are distinct functional differences among adipose cells depending on their location. For instance, gluteal–femoral fat cells in females have a higher lipoprotein lipase (LPL) activity, higher insulin receptor binding, and higher rates of non-insulin-stimulated and maximally insulin-stimulated rates of glucose transport and glucose metabolism, whereas omental adipose tissue contains more number of glucocorticoid receptors (GR) compared with subcutaneous adipose tissue with similar Kd values, whereas LPL activity in subcutaneous adipose tissue is lower compared with omental adipose tissue. Leptin mRNA expression is higher in abdominal subcutaneous adipocytes compared with omental adipocytes, and subcutaneous adipose tissue produces less interleukin-6 (IL-6) and corticosterone and more tumor necrosis factor-
(TNF-) compared with mesenteric adipose tissue.3,4 In view of this, it is no surprise that there exists a controversy regarding the definition of obesity, the relationship between obesity and body mass index (BMI) and coronary heart disease (CHD), and other adverse events. On the basis of the cross-sectional study by Romero-Corral et al.,5 it was suggested that BMI does not have the discriminatory power to distinguish between lean mass and percentage of body fat, especially in those whose BMI is < 30 kg/m2.
Adipose cells produce a variety of adipokines. Since obesity is a low-grade systemic inflammatory condition and is commonly associated with CHD, it is important to know whether the obesity detected in a given subject is really significant or not. Previously, I suggested that those who appear to be obese (which ever definition is used to define it) if show normal plasma levels of various adipokines including adiponectin and abdominal adipose cell 11ß-HSD-1 (11ß-hydroxysteroid dehydrogenase type-1 enzyme) could be considered to have constitutional obesity, whereas obese with abnormal levels of these biological markers can be considered to be at high risk of developing other features of metabolic syndrome X and CHD and hence is considered pathological.6,7 It is likely that subjects at high risk of developing CHD, even when they appear to be apparently normal at the time of evaluation (such as those with strong family history of hypertension, type 2 diabetes mellitus, CHD, and hyperlipidemias), are more likely to have elevated IL-6, TNF-, macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine whose levels are regulated by TNF), and low IL-4, IL-10, adiponectin in their plasma, and elevated adipose tissue content of 11ß-HSD-1 compared with normal. A series of measurements of these biological markers (say once every year) may be necessary to know whether a particular individual continues to be normal or not. When these markers become abnormal it suggests that they are likely candidates to develop CHD and metabolic syndrome X in future.
In view of the functional differences among adipose cells based on their location, I propose that a functional study is more relevant and appropriate to label a subject as obese or not. Thus, those who are apparently obese or have high BMI but do not show changes in the levels of various indices such as hs-CRP, IL-6, TNF-, MIF, IL-10, IL-4, adiponectin, and 11-ß HSD-1 are likely to have constitutional obesity, whereas those who show changes in the concentrations of some, if not all, of these factors probably have pathological obesity and are at risk of developing CHD and other diseases associated with obesity such as hypertension, type 2 diabetes mellitus, dyslipidemia, and CHD. Hence, it is suggested that a detailed study is needed to define the characteristics of constitutional and pathological obesity that would help to resolve the association between obesity, BMI, and CHD.
References
- Das UN. A defect in the activity of
6 and 5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins Leukot Essen Fatty Acids (2007) 76:251–268.[CrossRef][Web of Science][Medline] - Das UN. Is metabolic syndrome X a disorder of the brain with the initiation of low-grade systemic inflammatory events during the perinatal period? J Nutr Biochem. (in press).
- Das UN. Sex differences in the number of adipose cells. XX vs. XY (2003) 1:132–133.
- Ramos EJB, Xu Y, Romanova I, Middleton F, Chen C, Quinn R, Inui A, Das UN, Meguid MM. Is obesity an inflammatory disease? Surgery (2003) 134:329–335.[CrossRef][Web of Science][Medline]
- Romero-Corral A, Somers VK, Sierra-Johnson J, Jensen MD, Thomas RJ, Squires RW, Allison TG, Korinek J, Lopez-Jimenez F. Diagnostic performance of body mass index to detect obesity in patients with coronary artery disease. Eur Heart J (2007) 28:2087–2093.
[Abstract/Free Full Text] - Das UN. Pathophysiology of metabolic syndrome X and its links to the perinatal period. Nutrition (2005) 21:762–773.[CrossRef][Web of Science][Medline]
- Das UN. Metabolic syndrome X is a low-grade systemic inflammatory condition with its origins in the perinatal period. Curr Nutr Food Sci. (in press).
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