The Role of Gluten in Weight Gain: Part 1


If you have read the book “Wheat Belly” you are likely familiar with the idea that wheat is a cause of weight gain and that it is “as sugary as a Snicker’s Bar” metabolically speaking. While I believe there are some interesting points in that book I do not agree with everything stated in it. I do however believe that wheat is not the “health-food” it has been labelled to be.  I am of the opinion that the main protein in wheat, gluten, has some interesting and nasty effects on our gut health, systemic inflammation, and our overall internal milieu.

There has been a lot of debate on the role of gluten in autoimmune disorders and whether or not those individuals who do not present with coeliac disease are at risk for autoimmune diseases due to dietary gluten intake. I believe this debate is being won by those supporting the role of gluten in a wide range of autoimmune disorders in non-celiac individuals.  Dr. Alessio Fasano, at the University of Maryland has indeed implicated wheat gluten in the causation of “Leaky Gut” and the autoimmune disorders that follow. The post today however is on a different topic, the role of gluten in weight gain.

Is it possible for gluten to contribute to weight gain/obesity and can the addition of gluten in your have a deleterious effect on your metabolism? The short answer is yes, it appears that gluten plays a role in causing inflammation, which in turn increases insulin resistance, glucose homeostasis, insulin resistance, fat oxidation, and even in promoting an atherosclerotic environment in vitro (1).  Typically I try to cover multiple papers in one post and amass the evidence to support an argument. This post is going to focus on one paper as it is the first of its kind and presents some exciting information and strong evidence for the role of gluten in weight gain and metabolic dysfunction. This paper “Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression” has been all over the Twitter/blogosphere and warrants a close look.

The paper is rather technical, so please bear with me as I try and explain their findings and the implications of what they found.

A group of Brazilian researchers conducted a study designed to examine the effect of gluten on weight gain, inflammation, glucose homeostasis, fat oxidation, leukocyte rolling and adhesion, and macrophage infiltration.  Essentially, these researchers purposefully over-fed mice for 8 weeks to increase their body weight (mimicking what is happening in America today) using a gluten free diet and a gluten containing diet and examined the effect it had one creating an internal milieu similar to metabolic syndrome and one that is “pro-atherosclerotic”.


The researchers did quite a comprehensive battery of tests to examine their metabolic and physiological states. The measurements included the following: fat mass, blood glucose, triaglycerol, total cholesterol, insulin, leptin, adiponectin, and resistin, Il—6, IL-10,  and TNF-alpha (inflammatory cytokines). They also measured leukocyte rolling and adhesion in vitro (how your white blood cells stick to your blood vessels and artery walls) and calculated a homeostasis model assessment of basal insulin resistance (HOMA-IR).  The last portion of their data collection was the most interesting to me and it measured the gene expression of specific genes that control glucose and fatty acid metabolism including, lipoprotein lipase (LPL), PPAR-alpha and gamma, hormone sensitive lipase (HSL), GLUT-4, and insulin receptor, as well as the gene expression of the previously mention cytokines and hormones.

That was a lot of data and maybe a little too technical for some people but here is the big picture of what they did. They were trying to take a “snap shot” of the metabolic and inflammatory status of these mice, which I feel they did an excellent job at accomplishing.


The results of the study are eye opening and do a great deal to explain the role gluten may play in exacerbating weight gain.  Instead of throwing numbers at you I will use the graphs from the study as they are quite clear and to the point.

Pic 1

What do we take away from these results?  Both groups, gluten free (GF) and the gluten consuming control (control) gained weight, had increased fat percent, increased total fat content, and fat cell area.  This was their goal as they intentionally attempted to fatten the mice. The interesting finding here is that the GF mice had lower weight gain, a lower increase in epididymal fat percent, lower total fat accumulation and a lower increase in fat cell area.  To summarize, the mice on a gluten free diet gained less weight and fat than those on a gluten containing diet.

 Pic 2

This graphic also has some interesting findings and implications on weight gain.  Mice on a GF diet had lower gene expression and serum concentration of the hormone Leptin.  This presents more data to the argument that increased leptin can lead to leptin resistance, which in turn can cause your body to lose control of accurately monitoring and assessing its own fat stores. The lower levels of leptin seen in the GF mice may help explain why they gained less weight. They were able to better control their weight gain through better regulation of their adipostat. Stephan Guyenet has an excellent presentation on this concept that can be found (here).

We also see greater gene expression and serum concentration of adiponectin in the GF mice compared to the control. Based upon the results of the weight gain this makes sense, as adiponectin levels are inversely associated with adiposity. As adiponectin plays a protective role in metabolic syndrome through regulation of glucose metabolism, increases insulin sensitivity and fatty acid oxidation as well as suppressing adhesion molecule suppression and cytokine release from macrophages (2).

The result of the resistin measure also follows the trend of the other measures in this graph with GF mice having lower serum levels of resistin.  Resistin is known to play a role in inflammation, LDL accumulation (this is especially problematic as accumulated lipoproteins in an inflammatory environment increases LDL oxidation), and insulin resistance (3).

  Pic 3

Did the difference in weight gain and hormone levels between the mice have any effect on metabolism and glucose control? This graphic strongly supports that conclusion. In the GF mice we observe lower fasting glucose, lower fasting insulin, lower HOMA-IR (a measure of insulin resistance), increased insulin and GLUT-4 receptor expression, and an increase in PPAR-gamma expression. The last measure, PPAR-gamma, is less well known in the general populous compared to glucose, insulin, and GLUT-4 so I will explain its function. PPAR-gamma is a nuclear receptor, a receptor found inside a cell, which stimulates lipid uptake and metabolism.  PPAR-gamma agonist drugs have been used to help treat hyperlipidemia and hyperglycemia. These drugs are commonly referred to as TZD’s and are a medication commonly used in the treatment of Type II diabetes.


This covers the first part of the paper.  As you can see this study presents some promising results and implications for a gluten free diet in attenuating weight gain.  This wraps up part 1 of this blog post and next week I will cover the last part of the paper and try and tie it all together as well as present my thoughts on the implications of this type of research as well as some critiques I have on the paper (no paper or study is ever perfect).  I will leave you with a few take home messages from what we have covered so far.

  • A gluten free (GF) diet in mice has shown to attenuate weight gain and fat accumulation when compared to a gluten containing diet
  • A GF diet results in lower leptin and resistin levels concomitantly with increased adiponectin levels when compared to a gluten containing diet. This indicates that a GF diet may help attenuate leptin resistance, inflammation, and metabolic control than a gluten containing diet.
  • Fasting glucose, insulin, and insulin resistance are lower in mice fed a GF diet than mice on a gluten containing diet. Fatty acid intake and metabolism are also increased in GF mice as shown by increased PPAR-gamma in those mice.  It appears that a GF diet maintains better glucose homeostasis and a better metabolic environment during weight gain than a gluten containing diet.
  • This does not clearly mean that gluten causes you to gain weight or be fat, but it does imply that a GF diet attenuates weight gain and the inflammation and compromised metabolic control that is associated with weight gain/obesity
One Response to “The Role of Gluten in Weight Gain: Part 1”
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  1. […] and HSL), along with nuclear receptor activity (PPAR).  To view my comments on these results see part 1 and part 2.  The last portion of the paper, and the topic of this post, is the role of gluten on […]

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