Monday, August 5, 2013

High Fish, Soy, Lard & Low Fat Diets: How Do They Affect Body Composition, Lipid and Glucose Metabolism? Results From Study on Rats That Don't Get Obese on High Fat Chow

(Un!)Surprising results: The "healthy" soy oil is the only fat in the study at hand that causes NAFLD.
I know, it is not certain whether or not the results of rodent studies will transfer to human beings and believe me, I would rather have seen this study conducted on humans or at least pigs. And while the latter are simply to expensive, the former are unreliable and don't like to be caged in metabolic wards... well, unless they receive a monetary compensation that costs about as much as a whole pigsty ;-)

That being said, let's stick with what we have and take a look at the results, Yoko Hashimoto and her colleagues published in a recent issue of the medical journal Lipids (Hashimoto. 2013).

The "obesity resistant" wistar rat and it's reaction to different dietary fats

I promise, the results are interesting and probably highly relevant, because the strain of Wistar rats (Slc:Wistar/ST) used in this study does not become obese simply because there is some fat in their chow. In fact, this is exactly the reason why the Japanese researchers picked the Wistar/STs. They wanted to examine the effects of various high-fat diets on plasma and hepatic lipid parameters and lipid metabolism in an obesity "resistant" rodent strain (everyone and every rat can become obese, but these don't get obese just by feeding them fatty chow) who were kept on either standard low fat chow or 3 different high-fat diets for 4 weeks (45% of the energy from fat) .
Figure 1: Fatty acid composition of the different diets (Hashimoto. 2013)
The primary outcomes of the study were the body and tissue weights, total food consumption, fatty acid composition, and energy metabolism, as well as the plasma and liver lipid profiles of the rodents.
Figure 2: Food intake, organ/body weight (Hashimoto. 2013)
If you take a look at the first set of results, namely the energy intake and body/organ weights, and focus on the distribution of white and brown fat you will realize that all rats on the high fat chow were significantly fatter than their low fat fed peers. For the fish oil group, however, the fat gain was almost exclusively from metabolically active brown fat.
Figure 3: Serum an liver lipid profiles (Hashimoto. 2013)
Against that background it is actually not surprising that the "fish oil rats" were the ones with the most favorable blood lipid profile. The rats in the soy group, on the other hand carried the highest amount of white fat and that also shows up in their messed up liver lipids.

The changes in the blood lipid levels the researchers observed went hand in hand with a few, but statistically significant differences in the local expression of important epigenetic regulators of fatty acid oxidation Acat1 / Acox1, in particular in the "fish oil rats":
Suggested read on the effects of fish oil on liver fat: "TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants?" (read more)
"Nineteen genes involved in inflammation response genes as well as lipid metabolism-related genes were selected and their mRNA expression levels were measured by qRT-PCR. No significant differences were detected between the groups in the expression levels of genes encoding microsomal triglyceride transfer protein (MTP), ACAT2, 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG- CoA R, EC, and prostaglandin-endoperoxide synthase 1 (PTGS1, COX-1). In contrast, the expression levels of Acat1 and Acox1 mRNAs were the most abundant (p < 0.01) in the livers of the [fish] group." (Hashimoto. 2013)
Interestingly enough, the fish oil group was yet not the only group with metabolically relevant changes in the genetic landscape of the liver:
"Lipogenesis was not significantly increased in the [soy] group [...] Moreover, the level of VLDL secretion in the [soy] group was lower than that in the [lard] group group, because the mRNA expression levels of Apob and Mttp were not up-regulated in the [soy] group. The normal levels of VLDL secretion contributed to hepatic lipid accumulation in the [soy] group"(Hashimoto. 2013)
Overall, the results of the study at hand do not simply highlight the differential effects of various forms of fatty acids on the development of metabolic derangements, they are also testimony to the fact that their effects on the metabolism of obesity-resistant Slc:Wistar/ST rats are much different from those of the obesity-susceptible animals that are usually used in studies like that. The latter become hyperphagic (ravenously hungry => overeating) and acquire hepatic lipid accumulation, almost irrespective of the source of dietary fat. The results of Hashimoto et. al. on the other hand demonstrate that "obesity-resistant Slc:Wistar/ST rats are isocaloric and do not exhibit hepatic lipid accumulation even when consuming high-fat diets, except one that includes soybean oil." (Hashimoto. 2013)

These results remind me of another SuppVersity article with the telling title "If You Go 'High Carb', You Better Go Really High! Seven Meals/Day, More than 800g of Carbs, Less Than 50g of Fat & 1000kcal Over Maintenance and Still Lean Gains!" (read more)
Bottom line: For me there are three messages to take away from this study. (1) The Slc:Wistar/ST rat could be a much better model to study the effects of high fat diets on human metabolism, than the regular rodents that are in fact actually selected for their high susceptibility to become obese on diets with 45% vs. just 11% of the energy in form of fat. (2) In a high fat diet scenario fish oil is the most effective way to keep the liver clean; the increase in body fat on the other hand is identical and the higher brown (=metabolically active) vs. white fat accumulation is probably irrelevant for humans. And what's more, if you take into consideration that all animals weighed the same at the end of the study, you just have to do the math to know that the "low fat rodents" were not just leaner, but also more muscular than their peers. (3) Lastly, there is the issue of omega-3 vs. omega-6 fatty acids where the comparison between the effects of lard and soybean oil do not contradict the importance of ratios, but still underline that the ratio interacts with the total PUFA (and omega-6) intake and that nothing compares to high soybean oil, when it comes to ruining your health deliberately.

  • Hashimoto Y, Yamada K, Tsushima H, Miyazawa D, Mori M, Nishio K, Ohkubo T, Hibino H, Ohara N, Okuyama H. Three Dissimilar High Fat Diets Differentially Regulate Lipid and Glucose Metabolism in Obesity-Resistant Slc:Wistar/ST Rats. Lipids. 2013 Aug;48(8):803-15