What Causes Insulin Resistance? Part I

Insulin is an ancient hormone that influences many processes in the body.  Its main role is to manage circulating concentrations of nutrients (principally glucose and fatty acids, the body's two main fuels), keeping them within a fairly narrow range*.  It does this by encouraging the transport of nutrients into cells from the circulation, and discouraging the export of nutrients out of storage sites, in response to an increase in circulating nutrients (glucose or fatty acids). It therefore operates a negative feedback loop that constrains circulating nutrient concentrations.  It also has many other functions that are tissue-specific.

Insulin resistance is a state in which cells lose sensitivity to the effects of insulin, eventually leading to a diminished ability to control circulating nutrients (glucose and fatty acids).  It is a major contributor to diabetes risk, and probably a contributor to the risk of cardiovascular disease, certain cancers and a number of other disorders. 

Why is it important to manage the concentration of circulating nutrients to keep them within a narrow range?  The answer to that question is the crux of this post. 

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New York Times Magazine Article on Obesity

For those of you who haven't seen it, Tara Parker-Pope write a nice article on obesity in the latest issue of NY Times Magazine (1).  She discusses  research showing  that the body "resists" fat loss attempts, making it difficult to lose fat and maintain fat loss once obesity is established.
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High-Fat Diets, Obesity and Brain Damage

Many of you have probably heard the news this week:

High-fat diet may damage the brain
Eating a high-fat diet may rapidly injure brain cells
High fat diet injures the brain
Brain injury from high-fat foods

Your brain cells are exploding with every bite of butter!  Just kidding.  The study in question is titled "Obesity is Associated with Hypothalamic Injury in Rodents and Humans", by Dr. Josh Thaler and colleagues, with my mentor Dr. Mike Schwartz as senior author (1).  We collaborated with the labs of Drs. Tamas Horvath and Matthias Tschop.  I'm fourth author on the paper, so let me explain what we found and why it's important.  

The Questions

Among the many questions that interest obesity researchers, two stand out:

1. What causes obesity?
2. Once obesity is established, why is it so difficult to treat?

Our study expands on the efforts of many other labs to answer the first question, and takes a stab at the second one as well.  Dr. Licio Velloso and collaborators were the first to show in 2005 that inflammation in a part of the brain called the hypothalamus contributes to the development of obesity in rodents (2), and this has been independently confirmed several times since then.  The hypothalamus is an important brain region for the regulation of body fatness, and inflammation keeps it from doing its job correctly.

The Findings

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Junk Free January

Last year, Matt Lentzner organized a project called Gluten Free January, in which 546 people from around the world gave up gluten for one month.  The results were striking: a surprisingly large proportion of participants lost weight, experienced improved energy, better digestion and other benefits (1, 2).  This January, Lentzner organized a similar project called Junk Free January.  Participants can choose between four different diet styles:

1. Gluten free
2. Seed oil free (soybean, sunflower, corn oil, etc.)
3. Sugar free
4. Gluten, seed oil and sugar free

Wheat, seed oils and added sugar are three factors that, in my opinion, are probably linked to the modern "diseases of affluence" such as obesity, diabetes and coronary heart disease.  This is particularly true if the wheat is eaten in the form of white flour products, and the seed oils are industrially refined and used in high-heat cooking applications.

If you've been waiting for an excuse to improve your diet, why not join Junk Free January?

A Sign of the Times

Every now and then, I venture out to go shopping at mainstream chain clothing stores.  Although I find it onerous, there are certain things I can't get at thrift stores.  For example, I can never find nice jeans.

The last time I set foot in these stores was about two years ago.  It was tough to find pants my size at that time-- many stores simply didn't sell pants with a 30 inch waist.  This year, it was even harder, since some of the stores that formerly carried 30W pants no longer did.  I managed to find my usual 30W 30L size in two stores, but I had a bizarre experience in both cases.   I put them on, and they were falling off my waist.  Since my waist size hasn't changed in two years, and my old 30W 30L pants of the same brand still fit the same as they did when I bought them two years ago, I have to conclude that both stores have changed their definition of "30 inches".  My new size is 28W 30L, which is tough to find these days.
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60 Minutes Report on the Flavorist Industry

A reader sent me a link to a recent CBS documentary titled "Tweaking Tastes and Creating Cravings", reported by Morley Safer.

Safer describes the "flavorist" industry, entirely dedicated to crafting irresistible odors for the purpose of selling processed and restaurant food.  They focused on the company Givaudin.  Dr. David Kessler, author of The End of Overeating, makes an appearance near the end.

Here are a few notable quotes:

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New Review Papers on Food Reward

As research on the role of reward/palatability in obesity continues to accelerate, interesting new papers are appearing weekly.  Here is a roundup of review papers I've encountered in the last three months.  These range from somewhat technical to very technical, but I think they should be mostly accessible to people with a background in the biological sciences. 

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction
Written by Dr. Nora D. Volkow and colleagues.  This paper describes the similarities between the mechanisms of obesity and addiction, with a focus on human brain imaging studies.  Most researchers don't think obesity is an addiction per se, but the mechanisms (e.g., brain areas important for reward) do seem to overlap considerably.  This paper is well composed and got a lot of media attention.  Dr. Volkow is the director of the National Institute on Drug Abuse, a branch of the National Institutes of Health.  The NIH is the main source of biomedical research funding in the US, and also conducts its own research.

Here's a quote from the paper:

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