Do Nerve Genes Determine Excess Skin Fat?
As any clinician knows, patterns of fat deposition tend to vary greatly even in people with similar amounts of total body fat. Not only are there the typical “male” and “female” patterns (commonly referred to as “apple” and “pear” shape) but there are also important differences in how much of excess fat is stored underneath the skin versus inside the abdomen or in other organs. These patterns of fat distribution have important consequences for the health risks associated with excess fat – excess skin or subcutaneous fat tends to have little impact on cardiometabolic risk (some even claim it may be protective) whereas excess fat stored in muscle or internal organs are linked to a wide range of health problems like diabetes, fatty liver disease, or sleep apnea. Why people differ in their propensity to deposit fat in these different locations is not entirely clear. Some of this is certainly regulated by sex hormones and cortisol but it has long been suspected that there may also be genetic factors at play. In a rather surprising twist, this notion is now supported by a paper just published in PLoS one by Kyung-Tai Lee and colleagues from the National Institute of Animal Science in Suwon, North Korea. Based on previous studies that showed a high heritability for backfat thickness (between 50% and 70%) and intramuscular fat (38% and 67%) content in pigs, Lee and colleagues first sequenced a region of pig chromosome 6 that had been shown to affect fatness traits in these animals. This led to the identification of 13 genes, 8 of which are interestingly also involved in psychiatric disorders and can affect nerve growth and function. All of these genes appeared to be related to back fat thickness (i.e. excess skin fat) rather than to muscle fat. The researchers next examined the relationship between markers of these genes and skin fat thickness in a cohort of 8,842 Korean individuals. Surprisingly 8 of the same genes that were associated with back fat in pigs were also associated with skin fat thickness in this population. (For expert readers, the 8 neuronal genes responsible for subcutaneous fat thickness were: NEGR1, SLC44A5, PDE4B, LPHN2, ELTD1, ST6GALNAC3, ST6GALNAC5, and TTLL7). From these studies the researchers conclude that common variations in these neuronal genes may surprisingly determine not only the genetic risk for obesity but also play an important role in the development of excess… Read More »
Kidney Fat Predicts Kidney Disease?
Yesterday, at the ongoing 2010 European Society of Cardiology, I attended as session focussing on the potential role of excess fat tissue that may surround blood vessels or the heart. Regular readers will recall, that the role of these fat depots have been a focus of my interest in past years. A new study by Olga Lamacchia and colleagues from the University of Foggia, Italy, published online in Nephrology Dialysis and Transplantation, suggests that increased fat deposition around the kidneys may also pose a risk marker for the development of chronic kidney disease in patients with type 2 diabetes. The researchers performed a cross-sectional study in 151 patients with type 2 diabetes that included measurements of kidney function, blood flow and ultrasound assessment of the fat surrounding their kidneys. Despite adjustment for both BMI and waist circumference, the amount of para- and perirenal fat predicted increases in renal resistance index and reduced glomerular filtration rate. Furthermore, in subjects with waist circumference above the diagnostic values of metabolic syndrome kidney function significantly and progressively declined across tertiles of para- and perirenal fat thickness. As explanations for this phenomenon, the authors discuss the potential role of increased intra-abdominal pressure of visceral obesity, direct physical compression of the kidneys, or mechanisms related to the secretion of adipokines and other factors by the surrounding fat tissue that may affect kidney function. For anyone familiar with kidney anatomy, it may also be of interest to recall that as fat deposition grows within the renal sinus, compression of various renal structures, especially of the inner medulla that, unlike the entire kidney, is not protected by the fibrous capsule, may occur. Increases in renal interstitial fluid hydrostatic pressure tends to compress the medullary vasa recta and tubules, reducing blood and tubular flow through the distensible loop of Henle, which could ultimately result in greater fluid, sodium and urate reabsorption. As my colleagues and I have previously suggested for epicardial fat, the authors suggest that measurement and recording of peri-renal fat should perhaps also be part of routine renal ultrasound assessments. Although this recommendation, may be a bit premature, the study nevertheless adds to the continuing literature demonstrating that in obesity and the accumulation of excess fat it is not just the “how much” but rather the “exactly where”, that ultimately determines the development of certain weight-related health problems. AMS Stockholm, Sweden You can now also follow me… Read More »
How Menopause Turns Women Into SWANs
Okay, I just couldn’t resist this headline – I hope my female readers will forgive this tongue-in-cheek title after they read the rest of the story. The acronym “SWAN” simply refers to the Study of Women’s health Across the Nation (SWAN) Fat Patterning Study, results of which are now published in a paper by Imke Janssen and colleagues from the Rush University Medical Centre in Chicago, in this month’s issue of OBESITY. This study examined the relationship between the male hormone testosterone and the accumulation of visceral fat (VF) in 359 women (47.2% black), aged 42-60 years randomly selected from the community. VF was measured using computer tomography. Bioavailable testosterone levels were strongly associated with the amount of VF independent of age, race, percent total body fat, and other cardiovascular risk factors. This study suggests that the previously described tendency for women to develop visceral adiposity as they go through menopause is probably related to an increase in biologically active testosterone levels that happens during the menopausal transition. As readers of these postings are probably well aware, male-pattern abdominal or belly fat deposition is a strong risk factor for the development of diabetes, hypertension, and other cardiometabolic risk factors. In contrast, female-pattern or lower-body obesity appears to be less dangerous and has even been associated with reduced risk of metabolic disease. This study links the increased bioavailability of the male hormone testosterone to the change in fat patterning observed during menopause. Interestingly, these higher levels of bioavailable (or bioactive) testosterone after menopause are not due to an increase in testosterone production but rather due to a decrease in sex-hormone binding-globulin (SHGB), possibly resulting from the menopausal decline in estrogen levels (a powerful stimulator of SHBG). (SHBG, as the name implies, normally binds testosterone, thereby rendering it biologically inactive – the less SHBG there is to bind testosterone, the more free testosterone there is around to do its thing) Of course, as a cross-sectional study, it is not possible to completely rule out the fact that other factors may lead to the accumulation of visceral fat, which in turn may lead to hormonal changes like higher insulin levels, which can also reduce SHBG levels. However, given the fact that fat precursor cells are known to have androgen (testosterone) receptors, the testosterone hypothesis certainly merits consideration. Whatever the precise mechanism, it certainly appears that menopause increases the risk of visceral fat accumulation… Read More »
Big Butts and Thighs Equals Lower Risk?
Regular readers are certainly familiar with my many posts on the limitations of BMI and on the idea that not all fat is bad and that different fat depots may have quite different effects on cardiometabolic risk. You can now find much more on this topic in a comprehensive review article by Konstantinos Manolopoulos and colleagues at Oxford University, UK, published in this month’s issue of the International Journal of Obesity. The review not only concludes that there is now ample evidence to support the notion that not just the amount of body fat, but rather its distribution is an important determinant of the metabolic and cardiovascular risk associated with obesity. In fact there is now increasing evidence that being too skinny may well be bad for you and that carrying a few extra pounds of fat on your hips and thighs may actually be protective. Thus, studies show that increased hip and thigh fat is independently associated with protective lipid and glucose profiles. This protective effect may be in part due to the fact that gluteofemoral fat can absorb and store excess fatty-acids, thereby removing them from the circulation. In addition, leptin and adiponectin levels tend to be positively associated with gluteofemoral fat while the level of inflammatory cytokines is negatively associated. As the authors point out, the loss of gluteofemoral fat, as observed in Cushing’s syndrome and lipodystrophy is in fact associated with an increased metabolic and cardiovascular risk. This may not be good news for people seeking medical help to reduce the size of their hips and thighs – I would probably have to advise them against it – definitely not a message many of my patients want to hear. On the other hand, if the excess fat is largely located around your midsection, then, this excess “belly” fat is probably the biggest driver of your risk for type 2 diabetes and heart disease. So really, not much new for regular readers of my blog, but certainly a noteworthy article that nicely summarizes what is currently known about this issue. Wonder what it’ll take to make large butts and thighs more socially acceptable? AMS Edmonton, Alberta
Metainflammation Determines Obesity Complications?
I am currently attending the 8th Academic Board Members Meeting of the International Chair on Cardiovascular Risk here in Boston. As always, Jean-Pierre Després (Université Laval), the Scientific Director of this chair, together with the local host, Peter Libby (Brigham and Womens, Harvard), have put together a remarkable program on the role of abdominal obesity in cardiometabolic disease – this time the focus is on inflammation. Readers of these pages, will be familiar with previous posts on the possible role of inflammation in the development of obesity related complications. This state of low-grade chronic inflammation is particularly found in people with visceral or ectopic fat. In his presentation, Gokan Hotamisligil (Harvard School of Public Health) used the term “metainflammation” to describe this state of low-grad inflammation that leads to inflammatory response in many tissues and has been postulated to play an important role in the many metabolic alterations like insulin resistance, type 2 diabetes, but also atherogenesis in blood vessels that can ultimately precipitate a stroke or heart attack. I was particularly enamored by the Jean Vague/Per Bjorntorp Award Lecture presented by Wilfred Y. Fujimoto, Professor Emeritus of Medicine, University of Washington, who talked about his remarkable long-term studies on Japanese Americans in which, using sequential computer tomography, his group was able to demonstrate the important role of visceral fat for the striking propensity to develop type 2 diabetes in this ethnic group. Clearly, this is an area of research, where much remains to be done before we fully understand why some people are more prone to the cardiometabolic complications of obesity than others. Click here for more on the various activities of the International Chair on Cardiometabolic Risk. AMS Boston, MA
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