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Transgenerational Transmission of Metabolic Disease

sharma-obesity-dna_molecule9If  anyone ever tells you that the current obesity epidemic can have nothing to do with genetics because “genes don’t change in a couple of generations”, it is completely fair to let them know that they probably do not know what they are talking about.

Indeed, there is now overwhelming evidence showing that a variety of health problems, particularly related to metabolic diseases including obesity, can well be transmitted from generation to generation as a result of epigenetic modifications that persist in subsequent generations, even if these are no longer exposed to the “trigger” environment.

Anyone who is interested in learning about how much we know about these intergenerational mechanisms, will probably want to read a recent review article on this subject by Rachel Stegemann and David Buchner, published in Seminars in Cell & Developmental Biology.

In this papers the authors review examples of transgenerational inheritance of metabolic disease in both humans and model organisms and how these can be triggered by both genetic and environmental stimuli.ors

As the authors note,

“A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation.”

They also discuss example of therapeutically targeting the epigenome (e.g. through dietary modification or exercise) to prevent the transgenerational transmission of metabolic disease.

These findings have substantial implications for our attempts to prevent or even reverse the development of obesity in future generations.

@DrSharma
Vancouver, BC

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Liraglutide 3 mg For Obesity: The SCALE Trial

saxendaThis week, the New England Journal of Medicine publishes the results of the SCALE Trial, a 56-week randomised controlled trial of liraglutide 3.0 mg vs. placebo (both groups got advice on diet and exercise), on weight loss and other metabolic variables.

The study, that enrolled about 3,700 subjects (70% of who completed the trial), showed greater clinically relevant weight loss in participants treated with liraglutide than with placebo.

Overall, at 56 weeks,

– 2 in 3 individuals on liraglutide achieved a 5% weight loss (compared to 1 in 4 on placebo).

– 1 in 3 individuals on liraglutide achieved a 10% weight loss (compared to 1 in 10 on placebo).

– 1 in 6 individuals on liraglutide achieved a 15% weight loss (compared to fewer than 1 in 20 on placebo).

The adverse effect profile was as expected from a GLP-1 analogue (mainly gastrointestinal and gall bladder related issues).

While liraglutide 3.o mg has now been approved as an anti-obesity agent in the US, Canada and Europe, its key downsides will likely be cost and the fact that it consists of a once-daily injection.

Obviously, as with any obesity treatment, discontinuation will likely result in weight regain (which is not unexpected, given that obesity, once established, becomes a chronic disease).

While in the US, where there are now 4 novel prescription medications for obesity, liraglutide 3.o mg will be the only novel anti-obesity drug available in Canada – a rather sorry state of affairs for those who need medical treatment for this condition.

Where exactly liraglutide will establish itself in the treatment of obesity in clinical practice remains to be seen (time will tell) – but for some patients at least (especially the high-responders), it will hopefully offer a useful adjunct to behavioural treatments.

@DrSharma
Edmonton, AB

Disclaimer: I have received honoraria for consulting and speaking from Novo Nordisk, the makers of liraglutide

 

 

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Canadian Obesity Network’s Toronto Chapter Takes Off

CON-Toronto Chapter Executive

CON-Toronto Chapter Executive

As regular readers may know, the Canadian Obesity Network is currently promoting the creation of local chapters across Canada. This is part of the Network’s strategy to continue growing and engaging researchers, health professionals, and others with an interest in obesity prevention and management to network and break down silos.

Following the very successful launch of local Obesity Network chapters in Calgary and Hamilton, last night saw the inaugural meeting of the Toronto Chapter (CON-YYZ), which got together to appoint their new executive and to exchange ideas on local activities that this chapter can pursue in the future.

I had the opportunity of joining in for part of this meeting via Skype and was delighted to see the diversity of attendees and their enthusiasm – certainly a promise of great things to come.

For anyone interested in learning more about how to start your own local CON chapter, more information is available here.

I look forward to seeing a number of new Obesity Network chapters created across Canada, as we continue to seek better ways to fight weight-bias, discrimination and find better ways to prevent and manage obesity.

@DrSharma
Edmonton, AB

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How Bariatric Surgery Improves Fatty Liver Disease

Fatty Liver

Fatty Liver

Last week I posted on the importance of non-acoholic fatty liver disease as one of the most common yet insidious consequences of obesity.

Now, a paper by Bower and colleagues from Imperial College London, published in Obesity Surgery, provides a systematic review of the impact of bariatric surgery on liver biochemistry and histology.

The review clearly shows that bariatric surgery is associated with a significant reduction in the steatosis, fibrosis, hepatocyte ballooning and lobular inflammation. Surgery is also associated with a reduction in liver enzyme levels, with statistically significant reductions in ALT, AST, ALP and gamma-GT.

However, there is considerable variability in these outcomes and between different types of interventions – clearly suggesting that more research on this issue is needed.

Nevertheless, at this time it appears that bariatric surgery may well be the most effective treatment for fatty liver disease.

@DrSharma
Edmonton, AB

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Do Preferences In Diet Matter For Weight Loss

sharma-obesity-fat-dietingAs regular readers are well aware, obesity is a chronic disease which simply means that any treatment you decide to pursue needs to be one you can stick with in the long-term (this applies as much to your diet as it does to taking an anti-obesity drug or, for that matter having surgery – when the treatment stops the weight comes back!).

That said, it would be easy to assume that if you chose (or otherwise have a say) in the kind of diet you think will help you manage your weight, you’d a) lose more weight and b) be more likely to keep it off.

As a randomised controlled study by William Yancy Jr. and colleagues from Duke University Medical Center, Durham, North Carolina, published in the Annals of Internal Medicine, neither of these assumptions may be true.

The researchers randomised 207 participants to two groups – a choice group in which participants had the choice of going either on a low-carbohydrate (less than 20 g/day) or low-fat diet (less than 30% energy from fat).

The non-choice group was not given this choice but were randomly assigned to either of these diets. Both groups were provided with group and telephone counseling for 48 weeks.

Of the 105 choice participants, 58% chose low-carb and 44% chose low-fat – 83% completed the study – and lost on average 5.7Kg.

Of the 102 non-choice participants, 52 % were assigned to low-carb and 48% to low-fat – 86% completed the study – and lost on average 6.7 Kg.

Of note, the actual reported intake of carb in the low-carb groups ranged between 45-80 g of carbs per day (down from about 200 g/day) while fat intake in this group increased from about 40 to 55% of total energy); In the low-fat group, actual fat intake, fell from about 40% at baseline to about 35% on the diet.

There were no difference in dietary adherence, physical activity or quality of life.

This study illustrates that whether or not you get to chose your preferred diet or not doesn’t matter – what does is that you stick with it.

Or as the authors put it,

“The double-randomized preference design of our study allowed us to determine that preference did not meaningfully affect weight loss. Moreover, the range of estimated weight differences between groups in the 95% CIs does not contain a clinically meaningful difference in favor of the choice group.”

Both findings may not be exactly what one may have predicted – which is exactly why we need these types of studies.

@DrSharma
Edmonton, AB

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