Thursday, May 7, 2020

Is There More To Obesity Than N-6 PUFA?

Peter at Hyperlipid has a series of posts [1, 2, 3] looking at the Surwit diet, an obesogenic rodent diet from Research Diets (D12330). [4]
"There is more to obesity than [n-6] PUFA (gasp)." [1]
Not so fast!

I was of course curious to see what Surwit et al were up to here. They have a very fat-agnostic view of diet: fat is fat. He changes the formulation of his high-fat, high sucrose (HH) diet from F1850 [5] to D12330 in 1992, but still uses the old studies as references for the new ones, despite switching from lard to hydrogenated coconut oil plus soybean oil.

Fat is fat. Or is it?
"...we used mice and precisely defined isocaloric diets to compare the metabolic effects of saturated fat from coconut oil, unsaturated fats from soybean oil and fructose. To our knowledge, this is the first study not only to compare the effects of these three dietary factors in mice, but also to perform genome-wide expression profiling and metabolomics analysis of livers from animals fed a soybean-oil enriched diet." [6]
"Four isocaloric diets with 4.87 kcal/gm (5.56 kcal total) (Table 1) were formulated in conjunction with Research Diets, Inc. (New Brunswick, NJ). The diets are based on the Surwit diet..."
1.2 kcal% (control) vs 2.2 kcal% vs 10 kcal% from n-6 linoleic acid (LA).

The title says it all: [6]
"Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver"
She was subsequently hired to show that low-LA GMO soybean oil (Plenish) is less obesogenic than regular soybean oil. [7] Which she did. [8]

Neat bit:
"One of these genes, Pdk4, which was upregulated in SO-HFD livers, is known to inhibit the pyruvate dehydrogenase complex that links the TCA cycle with glucose and fatty acid metabolism. Repression of the pyruvate dehydrogenase complex shifts the balance towards gluconeogenesis which could result in hyperglycemia [76]. Consistent with our findings are reports that PDK4 expression is increased in diabetics [122] and that Pdk4-/- mice are resistant to HFD-induced hepatic steatosis and are more glucose tolerant [123,124]. Thus Pdk4 upregulation may be a contributing factor to both lipid accumulation in the liver and the development of diabetes and glucose ntolerance in SO-HFD mice." [6]
That could be a problem...

Lots more interesting findings. Pity Surwit didn't have a more nuanced view of fat.

There's definitely more to obesity than just n-6 fats. But they do seem to play a central role.

(I was looking for some sort of explanation as to why Surwit had switched from F1850 to D12330, and changed the fat used but still added soybean oil. Couldn't find it; Research Diets just mentions that he called them up and specified what became D12330 aka D12331.)

This was originally posted as a comment at [1], there may be responses there.

P.S. Peter replied:
"Ha! These people are so superficial. PDK4 is upregulated in the liver of diabetics because that's how gene expression tries to protect you from the ministrations of the PUFAphiles. PDH complex probably down regulates because normal soybean oil is supplying a sh!tload of low FDAH2:NADH linoleic acid which means the supply of acetyl-CoA will be in excess of the cell's needs and getting more from pyruvate is not needed. So the liver uses PDK4 to avoid even more of a disaster than the cardiologists are pushing for... 
"Just looking down at the ETC level. 

Dobromylskyj P. Surwit diet and derivatives. Hyperlipid. Published April 30, 2020. Accessed May 7, 2020.

Dobromylskyj P. Surwit diet and derivatives (2) It’s the insulin. Hyperlipid. Published May 2, 2020. Accessed May 7, 2020.

Dobromylskyj P. Surwit diet and derivatives (3) 5LJ5 vs D12330: Chow vs Surwit. Hyperlipid. Published May 4, 2020. Accessed May 7, 2020.

D12331 Formula - OpenSource Diets. Research Diets, Inc. Accessed May 7, 2020.

Mouse Diet, High Fat, Fat Calories (60%), Paste. Bio-Serv. Accessed May 7, 2020.

Deol P, Evans JR, Dhahbi J, et al. Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver. PLoS One. 2015;10(7):e0132672-e0132672. doi:10.1371/journal.pone.0132672

GM soybean oil causes less obesity and insulin resistance but is harmful to liver function: Mouse study compares Plenish to conventional soybean, coconut, and olive oils. ScienceDaily. Accessed May 7, 2020.

Deol P, Fahrmann J, Yang J, et al. Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice. Scientific Reports. 2017;7(1):1-13. doi:10.1038/s41598-017-12624-9