Arya M. Sharma

Obesity prevalence from a European perspective: a systematic review

BackgroundObesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss current epidemiological data on the prevalence of obesity in European countries.MethodsWe identified relevant published studies by means of a MEDLINE search (1990–2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each countrys overall population.ResultsIn Europe, the prevalence of obesity (body mass index ≥ 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe.ConclusionIn Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.

Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.

A growing amount of evidence suggests that regional fat distribution plays an important part in the development of an unfavorable metabolic and cardiovascular risk profile. Epicardial fat is a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function. This small, visceral fat depot is now recognized as a rich source of free fatty acids and a number of bioactive molecules, such as adiponectin, resistin and inflammatory cytokines, which could affect the coronary artery response. The observed increases in concentrations of inflammatory factors in patients who have undergone coronary artery bypass grafting remain to be confirmed in healthy individuals. Furthermore, epicardial adipose mass might reflect intra-abdominal visceral fat. Therefore, we propose that echocardiographic assessment of this tissue could serve as a reliable marker of visceral adiposity. Epicardial adipose tissue is also clinically related to left ventricular mass and other features of the metabolic syndrome, such as concentrations of LDL cholesterol, fasting insulin and adiponectin, and arterial blood pressure. Echocardiographic assessment of epicardial fat could be a simple and practical tool for cardiovascular risk stratification in clinical practice and research. In this paper, we briefly review the rapidly emerging evidence pointing to a specific role of epicardial adipose tissue both as a cardiac risk marker and as a potentially active player in the development of cardiac pathology.

Periadventitial fat releases a vascular relaxing factor

Virtually all blood vessels are surrounded by adventitial fat. Adipocytes produce a host of vasoactive substances that may influence vascular contraction. We tested whether or not perivascular adipose tissue modulates contraction of aortic ring preparations. We studied aortic rings surrounded by periadventitial adipose tissue from adult Sprague‐Dawley rats. At a maximum concentration of 300 nM angiotensin II, 6.5 μM serotonin, and 5 μM phenyleph‐rine, the contractile response of intact rings was 95%, 80%, and 30% lower than that of vessels without periadventitial fat. The anticontractile effect of periad‐ventitial fat was reduced by inhibition of ATP‐dependent K+ channels with glibenclamide (3 μM) and by the tyrosine kinase inhibitor genistein (10 μM). Blocking NOS, cyclo‐oxygenase, cytochrome P450, or adenosine receptors did not restore the vascular response in intact vessels. The anticontractile effect of perivascular fat was present in Zucker fa/fa rats, suggesting that leptin receptors were not responsible. Transferring the bath solution from intact vessels, isolated periadventitial tissue, and cultured rat adipocytes to precontracted vessels lacking periadventitial fat resulted in a rapid relaxation. We suggest that perivascular adventitial adipose tissue releases a transferable adventitium‐derived relaxing factor that acts by tyrosine kinase‐dependent activation of K+ channels in vascular smooth muscle cells..—Löhn, M., Dubrovska, G., Lauterbach, B., Luft, F. C., Gollasch, M., Sharma, A. M. Periadventitial fat releases a vascular relaxing factor. FASEB J. 16, 1057–1063 (2002)

The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin-angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin-angiotensin system in the metabolic syndrome.

Angiotensin Blockade Prevents Type 2 Diabetes by Formation of Fat Cells

Obesity is the prime risk factor for the development of type 2 diabetes. Recent clinical trials have shown that blockade of the renin-angiotensin system, either by inhibiting the angiotensin-converting enzyme or blocking the angiotensin type 1 receptor, may substantially lower the risk for type 2 diabetes. The mechanism underlying this effect is unknown. Based on our recent observation that angiotensin II markedly inhibits adipogenic differentiation of human adipocytes via the angiotensin type I receptor and that expression of angiotensin II-forming enzymes in adipose tissue is inversely correlated with insulin sensitivity, we propose the hypothesis that blockade of the renin-angiotensin system prevents diabetes by promoting the recruitment and differentiation of adipocytes. Increased formation of adipocytes would counteract the ectopic deposition of lipids in other tissues (muscle, liver, pancreas), thereby improving insulin sensitivity and preventing the development of type 2 diabetes.

Haplotypes of Angiotensinogen in Essential Hypertension

The M235T polymorphism of the angiotensinogen gene (AGT) has been associated with essential and pregnancy-induced hypertension. Generation of haplotypes can help to resolve whether the T235 allele itself predisposes to the development of hypertension or acts as a marker of an unknown causal molecular variant. We identified 10 diallelic polymorphisms at the AGT locus and genotyped both a series of 477 probands of hypertensive families and 364 controls, all French Caucasians, as well as a series of 92 hypertensives and 122 controls from Japan. Despite a large ethnic difference in gene frequency, a significant association of T235 with hypertension was observed both in Cancasians (.46 vs. .38, P = .004) and in Japanese (.91 vs. .76, P = .002). In both groups, the G-->A substitution located at position -6 upstream of the initial transcription site occurred at the same frequency and in complete linkage disequilibrium with the T235 allele. No other polymorphism was found to be consistently associated with hypertension. Five informative haplotypes subdividing the T235 allele were generated. Whereas two of them were associated with hypertension in Caucasians, none of these two haplotypes (H3 and H4) reached statistical significance in Japanese. The analysis of the AGT-GT repeat revealed marked linkage disequilibriums between each of the diallelic polymorphisms and some (GT)n alleles, with similar patterns in the two populations. The strong disequilibrium between M235 and (GT)16 explained the increased frequency of that particular allele in French controls compared with hypertensives (.42 vs. .36, P < .01). The haplotype combining the M235T and G-6A polymorphisms appears as the ancestral allele of the human AGT gene and as the one associated with hypertension.

Hypothesis: β-Adrenergic Receptor Blockers and Weight Gain

One of the arguments put forward against the primary use of β-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted ≥6 months, body weight was higher in the β-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range −0.4 to 3.5 kg). A regression analysis suggested that β-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of β-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of β-blocker treatment.

Association between the angiotensinogen 235T-variant and essential hypertension in whites a systematic review and methodological appraisal

Recently, an allelic variant of the angiotensinogen gene (AGT 235T) has been associated with increased risk of hypertension. However, this finding has not been confirmed by all investigators. A meta-analysis was performed to examine the association between the AGT 235T-allele and hypertension in whites and to identify potential reasons for the controversial results. All relevant articles published between 1992 and 1996 were identified through multiple sources. The studies were methodologically appraised, and the frequency of the AGT 235T-allele was extracted. The 235T-allele frequency was pooled using the common odds ratio (OR) estimator by Mantel-Haenszel. Homogeneity was assessed using the Breslow-Day test. Together these studies present data on 5493 patients. The AGT 235T-allele was significantly associated with hypertension (OR: 1.20; 95% [CI]: 1.11 to 1.29; P<.0001). This association increased in studies with positive family history (OR: 1.42; 95% CI: 1.25 to 1.61, P<.0001), recruitment of cases from referral centers (OR: 1.39; 95% CI: 1.20 to 1.62, P<.0001), and more severe hypertension (OR: 1.34; 95% CI: 1.22 to 1.47, P<.0001). However, the presence of methodological problems in all studies gives rise to serious concerns regarding bias and confounding. Despite a statistically significant, albeit weak, association between the AGT 235T variant and hypertension that has been confirmed through sensitivity analysis, this finding has to be interpreted with caution, as the methodological weaknesses of the individual studies are likely to have biased the outcome of the meta-analysis. Clearly, more rigorous methods need to be applied in association studies on the genetics of human hypertension.

Hormonal regulation of the human adipose-tissue renin-angiotensin system: relationship to obesity and hypertension.

Objective Adipose tissue secretes vasoactive substances which may contribute to the development of obesity-related hypertension. The aim of this work was to study the expression of renin–angiotensin system genes in adipose tissue of obese hypertensive subjects and the hormonal regulation of these genes. Design Differential expression of renin–angiotensin system genes in subcutaneous abdominal adipocytes of 12 lean normotensive, eight obese normotensive, and 10 obese hypertensive women was determined in a cross-sectional study. In vitro hormonal regulation of these genes was studied in primary human adipocytes obtained by breast reduction from healthy women. Methods In the clinical study, 24-h ambulatory blood pressure measurement and anthropometry were used to characterize the volunteers, and adipocytes were obtained by subcutaneous needle biopsy. The in vitro regulation of renin–angiotensin system genes by hydrocortisone, insulin, thyroxin, estradiol and angiotensin II on primary cultured human mammary adipocytes was studied by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results While expression of the angiotensinogen gene was significantly lower in adipocytes from both obese groups, the renin, angiotensin-converting enzyme and angiotensin II type 1 receptor genes were significantly upregulated in obese hypertensives. Hydrocortisone increased angiotensin II type 1 receptor gene and protein expression in a time- and dose-dependent manner in human adipocytes, but had no significant influence on other renin–angiotensin system genes. Expression of these genes was not significantly affected by any of the other tested hormones. Conclusions Renin–angiotensin system genes are differentially regulated in human obesity and hypertension. The role of the adipose-tissue renin–angiotensin system in the development of obesity-associated hypertension or metabolic disease clearly warrants further study.

Threshold Values of High-risk Echocardiographic Epicardial Fat Thickness

Objective: Echocardiographic epicardial adipose tissue is a new index of cardiac and visceral adiposity with great potential as a diagnostic tool and therapeutic target. In this study, we sought to provide threshold values of echocardiographic epicardial fat thickness associated with metabolic and anthropometric risk factors.