Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4).  Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity.  Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects.  This immediately raises two questions:

1. Does metabolically healthy obesity exist?
2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

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Ancestral Health Symposium 2012

I recently returned from AHS12 and a little side trip to visit family.  The conference was hosted at Harvard University through the Harvard Food Law Society.  Many thanks to all the organizers who made it happen.  By and large, it went smoothly.

The science as expected ranged from outstanding to mediocre, but I was really encouraged by the presence and enthusiastic participation of a number of quality researchers and clinicians. The basic concept of ancestral health is something almost anyone can get behind: many of our modern health problems are due to a mismatch between the modern environment and what our bodies "expect".  The basic idea is really just common sense, but of course the devil is in the details when you start trying to figure out what exactly our bodies expect, and how best to give it to them.  I think our perspective as a community is moving in the right direction.

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New Review Paper by Yours Truly: High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease

My colleagues Drs. Mario Kratz, Ton Baars, and I just published a paper in the European Journal of Nutrition titled "The Relationship Between High-Fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease".  Mario is a nutrition researcher at the Fred Hutchinson Cancer Research Center here in Seattle, and friend of mine.  He's doing some very interesting research on nutrition and health (with an interest in ancestral diets), and I'm confident that we'll be getting some major insights from his research group in the near future.  Mario specializes in tightly controlled human feeding trials.  Ton is an agricultural scientist at the University of Kassel in Germany, who specializes in the effect of animal husbandry practices (e.g., grass vs. grain feeding) on the nutritional composition of dairy.  None of us have any connection to the dairy industry or any other conflicts of interest.

The paper is organized into three sections:

1. A comprehensive review of the observational studies that have examined the relationship between high-fat dairy and/or dairy fat consumption and obesity, metabolic health, diabetes, and cardiovascular disease.
2. A discussion of the possible mechanisms that could underlie the observational findings.
3. Differences between pasture-fed and conventional dairy, and the potential health implications of these differences.

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Is Sugar Fattening?

Buckle your seat belts, ladies and gentlemen-- we're going on a long ride through the scientific literature on sugar and body fatness.  Some of the evidence will be surprising and challenging for many of you, as it was for me, but ultimately it paints a coherent and actionable picture.

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What Causes Insulin Resistance? Part VII

In previous posts, I outlined the factors I'm aware of that can contribute to insulin resistance.  In this post, first I'll list the factors, then I'll provide my opinion of effective strategies for preventing and potentially reversing insulin resistance.

The factors

These are the factors I'm aware of that can contribute to insulin resistance, listed in approximate order of importance.  I could be quite wrong about the order-- this is just my best guess. Many of these factors are intertwined with one another. 
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The Brain Controls Insulin Action

Insulin regulates blood glucose primarily by two mechanisms:

1. Suppressing glucose production by the liver
2. Enhancing glucose uptake by other tissues, particularly muscle and liver

Since the cells contained in liver, muscle and other tissues respond directly to insulin stimulation, most people don't think about the role of the brain in this process.  An interesting paper just published in Diabetes reminds us of the central role of the brain in glucose metabolism as well as body fat regulation (1).  Investigators showed that by inhibiting insulin signaling in the brains of mice, they could diminish insulin's ability to suppress liver glucose production by 20%, and its ability to promote glucose uptake by muscle tissue by 59%.  In other words, the majority of insulin's ability to cause muscle to take up glucose is mediated by its effect on the brain. 

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Fast Food, Weight Gain and Insulin Resistance

CarbSane just posted an interesting new study that fits in nicely with what we're discussing here.  It's part of the US Coronary Artery Risk Development in Young Adults (CARDIA) study, which is a long-term observational study that is publishing many interesting findings.  The new study is titled "Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis" (1).  The results speak for themselves, loud and clear (I've edited some numbers out of the quote for clarity):
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Food Reward: a Dominant Factor in Obesity, Part III

Low-Fat Diets

In 2000, the International Journal of Obesity published a nice review article of low-fat diet trials.  It included data from 16 controlled trials lasting from 2-12 months and enrolling 1,910 participants (1).  What sets this review apart is it only covered studies that did not include instructions to restrict calorie intake (ad libitum diets).  On average, low-fat dieters reduced their fat intake from 37.7 to 27.5 percent of calories.  Here's what they found:
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Oltipraz

Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.

Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.

A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.

The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.

This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.