Tuesday, December 25, 2012

Beyond Celiac: Study Sheds New Light on Obesogenic Effects of Gluten - Are PPARs & Bacteria Both Involved?

Cornflakes peanut butter cookies - guaranteed not gluten free ;-)
With Christmas Eve being over, and grandma's cookies, Christmas stollen, and all sorts of other stuff from the bakery in front of you (literally), Christmas Day may actually prove to be a way more "dangerous" than Christmas Eve - not just because of the total amount of calories, but also because of the low satiety effect of these sweet treats.

A recent paper by scientists from the Universidade Federal de Minas Gerais in Belo Horizonte in Brazil does now point to another reason you better give those bakery products a wide berth - not just, but especially with the energy overshoot on Christmas day: Gluten!

Study confirms for the first time what scientists and laymen alike have been speculating about

In what the scientists claim is the first well-controlled study of the effects of gluten intake on metabolic health in a non-celiac, but Western-style diet scenario, FabĂ­ola Lacerda Pires Soares and her colleagues put two groups of C57BL/6 mice on identical, iso-caloric high fat (hypercaloric) diets that differed only in terms of the amount of gluten that was added to the chow (0% gluten vs. 4.5% gluten).

Interestingly, the gluten diet did not influence any of the usual suspects, like food intake, total fat-free mass, fecal lipids excretion, blood lipid profile, blood total protein and ectopic (liver and muscle) lipid concentration (if you look closely you will realize that the gluten-free group actually had higher TRIGs, although the difference did not reach statistical significance).
Figure 1: Usual suspects and closer look at the effects 8 weeks gluten supplemented vs. gluten-free diets had on serum markers of metabolic syndrome and visceral fat parameters (Soares. 2012)
The data in figure 1 (right) does yet also show that the gluten content of the diet did nevertheless have a significant impact on the total body mass, visceral fat mass, lipid content and most importantly the adipocyte size.
Figure 2: Absolute adipokine levels (left) and fasting glucose and insulin levels, as well as Homa-IR (Soares. 2012)
Add to that the blunted expression of the anti-inflammatory and anti-diabetic fat hormone adiponectin and the increased the >5x higher expression of leptin (figure 2). And mix that with the reduced expression of PPAR-alpha and gamma of which Soares et al. argue that they may well be the key factor in the detrimental modulatory effect the addition of gluten had on the visceral fat structure and the lowered expression of the fat liberating enzymes LPL and and HSL, as well as reduced levels of the fat burning proteins ACC and CPT-1 (figure 3).
Figure 3: PPAR-alpha, -gamma, LPL, HSL, ACC and CPT-1 expression compared to rodents on regular chow (left); crown like structures in stained slices from visceral fat, inflammatory markers TNF-alpha and IL-6 (Soares. 2012)
So, even if the initially mentioned blood markers (aka the usual suspects) would suggest that both the gluten-consuming and gluten-free rodents were similarly bad off, the profound difference in inflammatory markers within the adipose tissue and the presence of comparatively many necrotic and inflammatory adipocytes in the crown like structures stand in line with increases in HOMA-IR, fasting glucose and insulin and an already compromised glucose clearance which are well-known harbingers of the metabolic syndrome.

These observations do not simply shed a whole new light on a hitherto largely ignored contributer to the etiology of the metabolic syndrome, they do also show that one of the reasons it has not been identified before is an over-reliance on BMI, total fat mass and serum lipids in the early stages of diabesity.

Reardless of whether the gut microbiome is part of the mechanism by which gluten predisposes the development of metabolic syndrome. Eating more inulin- and beta-glucan rich foods like Jerusalem artichokes, agave, bananas, onion, steel cut oats, wild yams, yacon, etc. certainly won't hurt your efforts to get lean, stay lean and leave the role of the obese diabetic to the other (read more)
Bottom line: The study at hand provides a good reason to limit your intake of "healthy whole grains" and other gluten containing foods, regardless of whether you suffer from celiac or not. Whether the established detrimental effects of gluten on the integrity of the intestinal wall and the increased leakage of bacterially produced endotoxins from the highly unfavorably changes in the gut microbiome in response to the high fat diets (Hildebrandt. 2009) are part of, or even the primary cause of these observations still has to be elucidated. The same goes for strategies to counter the translocation of the endotoxins across the gut lining (cf. "Shedding some light on the leaky gut") and the dose response relationship between the total amount of gluten in your diet and its effects on your metabolism. With 7% of pure gluten, it goes without saying that you would basically have to live of wheat in order to get to anywhere similar amounts of gluten in the diet... that said: Is it possible that the effects occur only in the presence of the high fat diet? After all, this alone has been shown to favor a pro-inflammatory gut microbiome.

You see there are enough questions to be answered in 2013 and the SuppVersity is going to be the place you will read the respective answers first ;-)

References:
  • Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009 Nov;137(5):1716-24.e1-2.
  • Soares FL, de Oliveira Matoso R, Teixeira LG, Menezes Z, Pereira SS, Alves AC, Batista NV, de Faria AM, Cara DC, Ferreira AV, Alvarez-Leite JI. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem. 2012 Dec 17.