Gluten and Weight Gain: Part 2

Unfortunately, I do not have a witty, well crafted introduction for this post so we might as well dive right into it.  I planned on making this a two part series but after re-reading the paper I decided I wanted to give this section and the very last section careful and thoughtful attention as there are some powerful implications from the results.  That being said, I have decided to make this a three part series.

(here is a link to the paper if you can’t remember it)


Figure A depicts the difference in gene expression of two different enzymes, hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) between the control group and the GF group.

HSL is an enzyme present within cells that hydrolyzes triaglycerols, and cholesterol esters.  HSL is activated when the body needs to mobilize its fat stores for energy. Put simply, HSL is responsible for freeing fatty acids from adipocytes so they can be burned for energy. In this study we see that GF mice have significantly higher levels of HSL than the control, indicating there may be increased fatty acid oxidation in the GF mice.  This speculation fits with the rest of the results, as we will discuss later.

LPL is an enzyme that catalyzes the hydrolysis of the triaglycerol component of circulating chylomicrons and VLDL.  This function of LPL provides non-esterified fatty acids (NEFA) to cells for substrate utilization.  One can think of LPL as a net or hook that snags fatty acids from passing molecules and brings them into the cell for utilization.   In this study the GF mice displayed higher levels of LPL than did the control mice. At first, I thought this indicates that the GF mice stored more fatty acids in their adipocytes as the cells they analyzed were indeed adipocytes; however, after reading through the whole paper and doing some pondering it appears this increase in LPL may actually beneficial as more fatty acids are being used for energy than in the control mice  due to the increased CPT-1 and PPAR-alpha.

Figure B depicts the difference in gene expression of two more enzymes, AcetylCoA carboxylase (ACC) and carnitine palmitoyl transferase-1 (CPT-1) between the control group and the GF group.  ACC is an intracellular enzyme that catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA (MCA). MCA is a key regulator of whether your cells utilize fatty acids for energy or synthesizes them.  Due to the fact there was no significant difference between the GF and control group, we will not explore the role of ACC much further.

CPT-1 is an enzyme located in the mitochondria, your cells power plant. CPT-1 is responsible for transporting long-chain fatty acids into the mitochondria to be utilized for energy by binding them to carnitine.  Think of CPT-1 this way, your mitochondria is a car and the fatty acid is the gasoline in the pump at the gas station. The nozzle and hose, which bring the gasoline into the car, is carnitine and CPT-1 is, if you live in states like Oregon where they pump your gas for you, the nice guy who puts the nozzle in the car tank and pulls the lever.  Without the nice guy pulling the lever, the gasoline can’t make it into your car.  In this study, the GF mice showed significantly higher levels of CPT-1 than the control.  This indicates there may be more fatty acid oxidation occurring in the GF mice than the control mice.

Now we arrive at my favorite part of the paper, Figure C.  Figure C is showing the difference in peroxisome proliferator-activated receptor alpha (PPAR-alpha) gene expression between the GF and control mice.  PPAR-alpha is a nuclear receptor that plays a major role in the regulation of lipid metabolism, and is often shown to be expressed in ketogenesis (1).  When PPAR-alpha is activated, there is an increase in the uptake, utilization, and catabolism of fatty acids.  When PPAR-alpha activation occurs we also see an upregulation of the genes involved in fatty acid transport (i.e. the CPT-1 mentioned earlier).  Pharmacological therapies that stimulate the upregulation of PPAR-alpha have been used in the treatment of hyperlipidemia (2,3).  In addition to the role PPAR-alpha plays in lipid metabolism, it also is a main contributor to regulating glucose homeostasis and improving insulin sensitivity (4).  For me, this result is the crowning jewel of the whole study. We see more than a two-fold increase in PPAR-alpha gene expression in GF mice than in the control.

What does all this mean?

When we compile all the results together we observe that a GF diet increases fatty acid oxidation, inhibits the buildup of triaglycerols in adipose tissue and improved glucose control.  The authors of the paper came to the same conclusions,

“Our results suggest that a gluten-free diet could inhibit the accumulation of triacylglycerol in adipose tissue by inducing concomitantly lipolysis of intracellular triglycerides (in- creased expression of HSL) and increasing mitochondrial oxidation of the fatty acids (released after HSL action) as suggested by the increased expression of CPT-1. Corroborating those results are the lower lipid accumulation in epididymal fat of GF mice and the similar lipid concentration in blood and liver. Our results also showed the protective effects of a gluten-free diet on glucose homeostasis. Glycaemia, insulinaemia, HOMA-IR and insulin sensitivity were all improved in the GF mice.” (5)

 Summing Up Part 2

The individual results have some powerful implications when they are taken as a whole.  In intentionally fattened mice fed a GF diet we observe what I argue to be “protective” physiological adaptations. The obese state is not optimal in terms of natural fitness and in the absence of preparation for hibernation, our body is designed to protect itself from excessive weight gain.  I believe we are observing this in the current study. The GF mice showed all of the necessary physiological signs of attempting to reduce the amount of weight gain. The GF mouse gained less weight and body fat, showed better blood lipid profiles, increased adiponectin and resistin, better glucose control, higher levels of GLUT-4 and insulin receptors, higher gene expression in hormones regulation and promoting fatty acid oxidation and increased gene expression in PPAR-alpha.  It appears that the addition of gluten in a diet may reduce the capability of an individual’s internal milieu to defend against unwanted weight gain.  The exact mechanism for this is not entirely clear at this point but I believe it starts with the deleterious effects it has on the gut, the role it plays in increasing systematic inflammation and autoimmunity.

The next post will cover the last portion of this study which implicates gluten may play a role in atherosclerosis.

One Response to “Gluten and Weight Gain: Part 2”
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  1. […] 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 inflammation […]

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