Dr. Sharma's Obesity Notes

Nikhil Dhurandar, PhD

Yes, the rapid spread of obesity around the world is reminiscent of the spread of an infectious diseases (albeit in slow motion), but is an obesity infection even possible?

Well, yesterday’s obesity news in the media was once again all about the obesity virus. These media reports were prompted by a new paper by Miloni Rathod and colleagues from Wayne State University, Detroit and the Pennington Biomedical Research Centre, Baton Rouge, published in Obesity.

This report is a follow-up to the many excellent studies from Nikhil Dhurandar’s group, which first suggested that the rather common human Ad36 virus may play a role in adipogenesis (formation of fat cells).

In the present study, using cultured mouse preadipocytes, the researchers demonstrated the following:

1) That the adenovirus Ad36 but not Ad2 stimulates fat accumulation as well as the expression of specific early, intermediate and late adipogenic marker genes in cultured mouse preadipocytes.

2) That treatment of adenovirus Ad36-infected cells with an antiadenoviral agent reduces fat accumulation in preadipocytes, demonstrating that viral mRNA expression is required for the process.

3) That although infection with adenovirus Ad36 amplifies the adipogenic response to a differentiation cocktail (containing insulin and other promoters of adipogenesis), this cocktail is not essential for Ad36 to induce formation of fat cells.

Thus, clearly, this human adenovirus can infect mouse cells to promote fat cell formation and it certainly appears worth the effort to try to elucidate exactly how this virus has this effect.

But what does this mean for human obesity?

Firstly, the Ad36 virus is extremely common and many people probably carry it - whether or not carrying this virus actually means that you are likely to gain more weight remains to be seen.

Secondly, it is important to remember that formation of fat cells in itself may not be a bad thing. After all, fat cells are the safest place to store extra calories. It is indeed widely believed that failure to accomodate excess calories in fat tissue (as a result of limited fat-cell formation) may promote fat deposition in other tissues (liver, muscle, heart), thereby promoting the development of metabolic risk factors like insulin resistance. Thus, infection with Ad36 may cause you to grow more fat cells, but may very well also turn out to actually decrease your risk for diabetes and other metabolic problems.

Thus, it will certainly be a while before antiviral treatments or even vaccinations will make it into our clinical armamentum for obesity prevention or management.

Nevertheless, it certainly is a good story and illustrates the fact that the study of obesity (and its origin) is anything but as simple or straightforward as many people believe.

AMS
Edmonton, Alberta

Regular readers of these pages are by now probably well aware of the fact that increased waist circumference (a rather crude measure of visceral fat) is considered a risk factor for coronary heart disease.

Nevertheless it may be worthwhile pointing out that the coronary artieries are not the only arteries affected - the same is true for peripheral arteries including the carotid vessels.

We are reminded of this by two recent papers in this month’s issue of the International Journal of Obesity.

In the first paper by Kim and colleagues from Pochon CHA University, Korea, common carotid artery intima-media thickness (IMT), waist circumeference (WC) and visceral fat thickness (VFT - measured by ultrasound) were measured in 368 men with type 2 diabetes.

Among the 174 subjects with abdominal obesity (WC >90 cm ), 35 subjects did not have visceral obesity (VFT<47.6 mm). In contrast, among the subjects without abdominal obesity (n=194), 88 patients had visceral obesity. Although there were no differences in age, glucose control, lipid profile and treatment modalities, subjects without abdominal obesity, but who had visceral obesity, had a higher carotid IMT compared with subjects with abdominal obesity, but without visceral obesity.

The authors conclude that in men with established type 2 diabetes, having visceral obesity, regardless of a normal WC, is a risk factor for increased carotid IMT, a measure of atherosclerotic burden.

In the second paper Maher and colleagues from Meath and National Children’s Hospital, Tallaght, Dublin, Ireland, studied 100 never smoking subjects (71 women, 29 men) without vascular events, with normal blood pressure, LDL cholesterol and glucose levels. Subjects underwent vascular measurements (Carotid intima-media thickness (IMT) using duplex ultrasonography, vascular stiffness assessment (Augmentation Index) by applanation tonometry and brachial artery reactivity tests).

Only age, waist-to-height-ratios and BMI were significant correlates of IMT in a multivariate analysis that included age, sex, systolic BP, HDLc and HOMA index. Augmentation Index correlated with age, waist-to-height-ratio and waist circumference, whereas brachial reactivity did not correlate with any anthropometric or metabolic parameters.

The authors concluded that even in in ‘healthy individuals’, anthropometric parameters and metabolic risk factors correlated with each other, but anthropometric parameters were the only significant correlates of carotid IMT.

Both studies together remind us of the importance of fat distribution, particularly the deposition of visceral fat, as a risk factor for cardiovascular risk.

AMS
Edmonton, Alberta

Smoking is well known to suppress appetite and many young smokers, especially women, smoke to control their weight.

Paradoxically, however, it turns out that smoking, at least in teenagers, strongly promotes the development of abdominal obesity - the dangerous fat that leads to diabetes, dysplipidemia and heart disease.

This at least is the observation reported by Suoma Saarni, University of Helsinki, Finland published in the American Journal of Public Health.

Using the FinnTwin16 sample, a prospective, population-based questionnaire study of 5 consecutive and complete birth cohorts of Finnish twins born between 1975 and 1979 (N=4296), studied at four points between the ages of 16 and 27 years, Saarni and colleagues analyzed the effect of adolescent smoking on abdominal obesity and overweight in early hood.

Smoking at least 10 cigarettes daily when aged 16 to 18 years increased the risk of abdominal obesity by around 30% for all participants. However, for women, the risk of becoming overweight after adjustment for possible confounders, including baseline BMI was almost 75% higher.

The authors conclude that teenage smoking is a risk factor for abdominal obesity among both genders but especially in women.

How smoking leads to abdominal obesity is not entirely clear. Are smokers prone to developing metabolic changes like insulin resistance or high sympathetic activity that may lead to abdominal fat? Are smokers more likely to become “addicted” eaters as they grow older (and stop smoking)? Are smokers less physically active than non-smokers, thereby becoming more prone to abdominal fat deposition? Do smokers make poorer food choices (e.g. more transfats)?

It appears that more work needs to be done before we fully understand the link - however, a clear message to those who smoke to control their weight - smoking is unhealthy, period.

Using tobacco to control weight makes no sense - a few pounds gained with smoking cessation are nowhere near the risk posed by continued smoking.

Quit now!

AMS
Jasper, Alberta

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Fatty Liver

Yesterday, I blogged about NAPEs, which are molecules secreted by the gut that affect food intake. Today, I draw attention to another newly discovered molecule called adropin (encoded by a gene called Enho), which is secreted by the liver in response to a high fat meal (adropin is also expressed in parts of the brain that regulate energy metabolism).

In this study, just out in CELL METABOLISM, Ganesh Kumar and colleagues from the Pennington Biomedical Research Centre (PBRC), Baton Rouge, LA, fed mice with a high-fat diet, resulting in increased secretion of adropin. However, as animals gained weight on the high-fat diet and developed insulin resistance and fatty livers, adropin levels dropped. 

Interestingly, in genetically altered mice that expressed high levels of adropin or with administration of exogenous adropin, animals were less likely to develop insulin resistance and fatty livers.

Together, the findings from this study suggest that adropin generation in the liver may play a role in the metabolic adaptation to high dietary fat intake.

Previous studies have shown that obese individuals show impaired metabolic flexibility and do not efficiently match fat oxidation with consumption. If adropin is indeed a metabolic signal to adapt substrate metabolism with fat intake, then the decline in adropin synthesis with obesity may be a factor in the impaired ability to match lipid metabolism with dietary fat intake, leading to the development of fatty livers, dyslipidemia, and glucose intolerance.

Given their findings, the authors conclude that adropin (or its target) may lead to new treatments for obesity-related metabolic disorders.

Obviously, it is still a long way from these findings in mice to treatments that are safe and effective in humans. Nevertheless, this study could be another stepping stone towards better understanding obesity and finding treatments that work.

AMS
Edmonton, Alberta
Hat Tip to Dennis Vance for bringing this study to my attention.

Non-Alcoholic Fatty Liver Disease (NAFLD), a common and widespread metabolic complication of obesity, is now the most common form of liver disease in the Western world. It is also an increasingly common cause of liver fibrosis, that can ultimately progress to cirrhosis and liver failure.

Currently, the accurate diagnosis of fibrosis requires a liver biopsy. Now researchers at the Mayo Clinic have reported that a new non-invasive technology called magnetic resonance elastography (MRE) can diagnose fibrosis with 97% accuracy in patients with NAFLD.

According to the Mayo Clinic press release:

“The technology, called magnetic resonance elastography (MRE), produces color-coded images known as elastograms that indicate how internal organs, muscles and tissues would feel to the touch. Red is the stiffest; purple, the softest. Other imaging techniques do not provide this information.” 

For the full press release, including access to a video demonstrating this novel technology click here.

AMS, Edmonton, Alberta