Hindsight: Epicardial Fat and Cardiovascular Risk
In 2005 I was joined by Gianluca Iacobellis at McMaster, with whom I published a paper in Nature Clinical Practice: Cardiovascular Medicine on the anatomic, biomolecular and clinical role of epicardial fat. In this paper we reviewed the growing evidence that epicardial fat is a metabolically active organ that generates various bioactive molecules, which could well affect cardiac function. We speculated that, although relatively small, this ‘visceral’ fat depot is 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. We also noted that epicardial fat mass might reflect intra-abdominal visceral fat and proposed that echocardiographic assessment of this tissue could serve as a reliable marker of visceral adiposity. Furthermore, epicardial adipose tissue is 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. Thus, we suggested that echocardiographic assessment of epicardial fat could serve as a simple and practical tool for cardiovascular risk stratification in clinical practice and research. While assessment of epicardial fat is not yet part of routine clinical assessment, since we published this paper, interest in this tissue has grown substantially and new research on the function of this tissue are now a recurring topic of interest at cardiovascular conferences around the world. AMS Edmonton, Alberta
All About The 3rd ‘M’
Regular readers will be quite familiar with the 4Ms of obesity (which incidentally feature quite strongly in the Obesity Network 5As of Obesity Management™). These are the four domains that need to be explored in every assessment for obesity and stand for Mental, Mechanical, Metabolic, and Monetary health. Last week, I co-hosted the International Hot Topics Conference on Obesity and Mental Health, which was all about the 1st M. This week, I am attending a conference that is all (and only about) the 3rd M, namely the Metabolic complications of obesity. As these are largely related to the presence of visceral and ‘ectopic’ fat, the conference is aptly named the International Congress on Abdominal Obesity (ICAO), and is currently being held in Quebec City. Despite this rather mono-dimensional view of obesity, ICAO nevertheless covers some of the most important complications of this condition – everything from diabetes and dyslipidemia to hypertension and heart disease (with a little bit of sleep apnea thrown in for good measure). The oral presentations are by a rather distinguished panel of speakers, and there are even a couple of satellite symposia sponsored by Danone, the Dairy Farmers of Canada, Pfizer, and Hoffman LaRoche. There is also a healthy dose of posters from attendees around the world – again focussed largely on metabolic health. I am certain that I will come away from this conference with plenty of new insights into the relationship between abdominal obesity and metabolic health – whether or not, I also come away with a better understanding of what to do about it, I guess, will remain to be seen. AMS Quebec City, Quebec
The Significance of Excess Fat in Non-Obese Individuals
Regular readers will be well aware that excess body weight, or even excess body fat, is not always associated with health risks. In contrast, it is now increasingly recognised that excess body fat (especially visceral fat), may constitute an important health risk even in individuals well below the conventional BMI cutoffs for obesity. Readers wishing to learn more about the nature of these so-called ‘lean-but-fat’ (LBF), ‘thin-on-the-outside fat-on-the-inside’ (TOFI) or ‘metabolically obese but normal-weight’ (MONW) individuals are directed to an excellent review article by Louise Thomas and colleagues from Imperial College London, UK published in Nutrition Research Reviews. As the article stems from the Metabolic and Molecular Imaging Group at Hammersmith Hospital, it contains a nice selection of MRI images depicting these different phenotypes. As the authors note, lean individuals with the typical metabolic phenotype more commonly associated with obesity “…have been shown to have reduced insulin sensitivity, increased abdominal adiposity, a more atherogenic lipid profile, and raised blood pressure, accompanied by physical inactivity and a low VO2max. The combination of these factors is thought to predispose ‘metabolically obese but normal-weight’ subjects to an increased risk of type 2 diabetes and CVD. This phenotype has been further refined using MRI to show disproportionate deposition of visceral adipose tissue, with many lean subjects having more visceral adipose tissue than overweight or obese subjects. This TOFI (thin-on-the-outside fat-on-the-inside) sub-phenotype has been observed in both male and female subjects, and increases an individual’s risk of metabolic disease.” As they further note, “Identifying subjects classified as TOFI may be important, since they may be at increased risk of metabolic disease compared with more obese subjects with less visceral fat. Incidence of ‘metabolically-obese but normal-weight’ has been reported to be between 13 and 18 %, which is similar to the incidence of TOFI (12 % women, 14 % men).” Overall, these finding are in line with our own observations that EOSS Stage 0 overweight and obese individuals, which comprise about 5-10% of the obese population, do not appear to have an increased risk for cardiovascular mortality, while over 50% of individuals in the BMI 25-30 range can meet the criteria for EOSS Stage 2 and 3 and with the same risk of cardiovascular complications as their obese counterparts. Unfortunately, despite the lower total amount of body fat, it appears that sustainably reducing body fatness is no less difficult in lean folks with excess body fat… Read More »
Hindsight: Angiotensin Blockade Prevents Type 2 Diabetes By Formation of Fat Cells?
Readers may recall last week’s Hindsight post on our paper in which we described our finding that angiotensin II inhibits the adipogenic differentiation of fat cells, and conversely, blocking the AT 1 receptor resulted in an accelerated differentiation of adipocyte precursor cells. While many would think that growing more fat cells may be a bad thing, it is important to remember that in a state of positive energy balance, the best place to store those extra calories is indeed in your fat tissue. Not being able to expand your fat tissue to accommodate excess calories may lead to the deposition of the extra fat in other tissues, which in turn, may prompt many of the metabolic problems associated with excess weight. This, at least, was the main tenor of a ‘hypothesis’ paper, we published in HYPERTENSION in 2002, in which we proposed the notion that blockade of the renin-angiotensin system may prevent the development of diabetes by promoting the recruitment and differentiation of adipocytes. This was based on our reasoning that the 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. Interestingly enough, this mechanism of diabetes prevention and treatment was harnessed by the use of thiazolidinediones also known as glitazones, a class of medications used in the treatment of type 2 diabetes. According to Google Scholar, this paper has been cited 257 times. AMS Edmonton, Alberta
South Asians Have Larger Fat Cells and Higher Risk
I am currently in Cambridge, UK, as part of the faculty of SCOPE (Specialist Certification of Obesity Professional Education), the official inter-professional educational program of the International Association for the Study of Obesity (IASO). This year’s participants include a significant delegation from India, which is in the midst of its very own obesity epidemic. While it is rare to see severe obesity (BMI levels over 40) in people of South Asian origin, there is now ample evidence suggesting that this population is particularly prone to the cardiometabolic complications of obesity even at a rather moderate increase in BMI. In a study I co-authored with Sonia Anand and other colleagues from McMaster University, Hamilton, ON, published online today in PLoS one, we show that this increased risk may be attributable to adipocyte hypertrophy and increased ectopic fat deposition. For this study, we recruited 108 healthy South Asians (defined as parents and grandparents who originated from India, Pakistan, Sri Lanka, or Bangladesh) and white Caucasians (ancestors originated from Europe) into one of three BMI strata: ≤25 kg/m2, 26–29 kg/m2, ≥30 kg/m2, matched for sex and age. Measurements included body composition, adipocyte size, abdominal fat area (MRI studies), and hepatic adiposity (MRI-spectroscopy) were assessed and related to fasting glucose, insulin, lipids and adiponectin levels. After adjustment for age, sex, and BMI, South Asians had more body fat, lower lean muscle mass, increased waist to hip ratio, less superficial subcutaneous abdominal adipose tissu, more deep/visceral to superficial adipose tissue ratio, and more liver fat than their Caucasian counterparts. South Asians also had higher fasting insulin, lower HDL cholesterol, and lower adiponectin levels. Most interestingly, fat cell size, measured as adipocyte area, was increased in South Asians compared to white Caucasians, and this difference in adipocyte size accounted for almost all of the observed differences in metabolic parameters and fat distribution. Thus, this form of ‘ethnic’ lipodystrophy’ may well play an important role in the increased risk of South Asians even at lower BMI levels. Although, this is a small cross-sectional study, the consistency of our findings with other reports in the literature, lead us to consider the following clinical implications: 1) Young, apparently healthy South Asians have greater metabolic impairment compared to white Caucasians who tend to develop metabolic changes at higher levels of obesity and at a more advanced age, supporting earlier screening for abdominal adiposity and elevated glucose among South Asians. 2)… Read More »
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