Wednesday, November 30, 2022

Sugar on your coconut oil?

I mentioned this paper in the last post:

Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver

In addition to looking at soybean oil they also looked at fructose. This is what eating 25% of your calories as fructose in your pelleted food does to your liver. Again red indicates lipid deposition in the liver.

First a reiteration of 5001 vivarium chow:


Then 25% fructose on the high coconut background:

















and on  the 10% soybean oil background
















So I think we can say that eating 25% of your calories as fructose might be excellent if you are a Bl/6 mouse who wants a fatty liver.

But what does fructose do to your weight/fatness?

That depends. If you are on coconut oil (+2% calories as linoleic acid) it increases your weight towards the weight of the soybean oil group.

If you are on soybean oil then including this much fructose decreases your weight to that of the coconut plus fructose group.

How come?

Sadly feeding mice on 25% of their calories as fructose generates rectal prolapses in 30-40% of those mice. And rectal prolapse is, in all probability, just a surrogate for chronic gut rot.

I would be very, very cautious about interpreting any of the data from mice with this degree of gut dysfunction. Which does nothing to allow me to decide whether the sucrose present in high "fat" diets such as the Surwit coconut/sucrose diet or any of several butter oil/sucrose diets is significant.

Which would be nice to know.

So let's look at a paper by Surwit's group:

Reversal of Diet-Induced Obesity and Diabetes in C57BL/6J Mice

All you have to do to reverse both obesity and diabetes in Bl/6 mice is remove the fat from the diet. 

Here are the compositions. The low fat diet always reversed the problems from high fat in a few months. For Bl/6 and A/J (less obesity prone) mice:






















If you glance down through the ingredients things look very similar except for the fat and carbohydrate composition. Right down to the inclusion of exactly 18.3g/kg of soybean oil to avoid essential fatty acid deficiency in each diet.

Aside: Of course most of the components are the same by weight. But not by calories. The high fat diet dilutes everything with saturated fat calories, by about 25%. This includes the linoleic acid from the 18.3g/kg of soybean oil. This is a very low (~roughly 1.6% kcal) LA diet. End aside.

Oh, and the sucrose. When the weights per kilogram of most components of the diets are identical to a decimal place, suddenly 10% of calories as sucrose arrives in the high fat diet. Why? Surwit discusses its inclusion and correctly points out that 10% sucrose in low fat diets does not cause obesity or diabetes in Bl/6 mice. But he does not address why the sucrose was "needed" in the high fat diet.

I leave you to speculate as to whether the sucrose is essential to the obesity model.

Okay, okay. I won't.

We just need this paper


The high fat diets contain about 40% of calories as MCT or long chain fats, both have around 1.6% of calories as linoleic acid. Oh, and were fed to rats, not Bl/6 mice. Here are the weight gains over the first month



















Essentially the MCT diet is the Surwit diet without the sucrose. Not exactly obesogenic. It strikes me that the sucrose is essential to develop pathology on high fat diets. If you want to call obesity pathology, see below.

The mechanism can be best summed up as "fructose is very complicated", ie I dunno.

Of course, as we do know, the obesogenic and diabetogenic Surwit diet is the one Jim Johnson's lab used for longevity/insulin gene studies. I blogged about it here.

They found reduced insulin exposure promoted peak longevity on standard mouse chow. However maximal median lifespan extension came from the Surwit diet despite the mice with "normal" insulin gene dose becoming obese and hyperinsulinaemic on said diet.

My take home message is that becoming fat and diabetic on a low linoleic acid (+ 5% fructose) diet is possible and may be aesthetically problematic but it doesn't carry the vast array of mid to late life illnesses associated with becoming obese using linoleic acid. Peak longevity may be a different matter.

The relevance of sucrose inclusion for obesity generation remains fascinating. I think it's real.

Peter

9 comments:

Basti said...

There are strong opinions out there that when it comes to fructose, rodents are not a good model. They are different to humans in especially this regard and so any lustig, Johnson, (or any other) research can be put straight in the toilet.

The difference is said to lie in the way the liver and gut handles fructose:

1. Rodents cant absorb it well. Humans can absorb tremendous amounts (when adequate glucose is copresent (aka a F:G ratio of approximately 1:1) .. which when consuming real food (fruit, honey, juices, etc), always is.
The non absorbed fructose in rodents will then be fermented and produce high LPS which will be primarily responsible for damaging the liver.
Again this does not happen in humans since it will be adequately absorbed.

2. In these rodent research, very ridiculously high amounts of fructose are given (often multiple cans of soda for a human equivalent) all at once. (And its pure fructose!)
Again this will lead to enormous gut fermentation and LPS and thus again this is what causes the issues and is not applicable to a high fructose (fruit, honey, juices) human diet.

3. The liver itself is not able to handle the fructose quite well as in humans.
The human liver, designed to supply the necessary glucose for the incredibly high human brains needs has a way bigger capacity to store glycogen and convert fructose to glucose and release it into blood.
Again rats are totally different.

So, would be nice if u could Adress these points.

Tucker Goodrich said...

Thanks for Parekh 1998, hadn't seen that one.

It raises a couple of thoughts.

Igarashi et al., 2015 (10.1016/j.bbalip.2015.05.006) found that sugar stimulated the endocannabinoid system, but to a less extent than LA, but via the same mechanism:

"Additionally, we report the unexpected finding that 7-day maintenance on a diet high in sucrose can also disable feeding-dependent OEA and LEA mobilization. The results suggest that FAE-mediated satiety signaling is suppressed by high fat or high sucrose in the diet, and that this suppression might contribute to hyperphagia and the development of obesity."

So if you have a high fat diet that's too low in LA, sucrose might substitute for it, in part.

Second, the other extra-mitochondrial LA obesity pathway is generation of the obesogen HNE, which of course only comes from LA and other n-6 fats. Cannizzaro et al., 2017 (10.1186/s12986-016-0149-z) measured the harm of a HFD (for maximal confusion, this is a High FRUCTOSE Diet):

“The level of HNE-modified proteins in plasma was increased almost 2-fold by HFD treatment, while RGZ completely normalized the level of HNE adducts (Fig. 6a).”

Which gets us back to Surwit. If you want to reduce the obesogenic effect of the Surwit diet, Chang et al., 2020 (10.21203/rs.3.rs-104384/v1) block the proliferation of HNE by stimulating the HNE detox pathway in the form of aldehyde dehydrogenase (ALDH):

“Importantly, the ALDH2 activator AD-9308 increased both the catalytic activity of WT and mutant enzyme, reduce serum 4-HNE levels, and effectively alleviated diet-induced obesity, fatty liver, insulin resistance, and glucose intolerance in both Aldh2-KI and WT mice in a dose-dependent manner.”

So sucrose/fructose is required to reduce the production of anti-obesogen OEA and stimulate production of obesogen HNE, in a low-LA environment?

cavenewt said...

Tangentially topical:

"Congress: Close the gap between funding for nutrition research and the toll diet-related disease takes on Americans"

https://www.statnews.com/2022/12/02/congress-close-the-gap-funding-nutrition-research-toll-diet-related-disease/

Hahahahaha

cavenewt said...

On a more serious note, this 2003 paper from the BMJ.

"HARLOT plc: an amalgamation of the world's two oldest professions" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300797/

Offering services like: 'Create consent forms in which study patients sign a “waiver of right to receive information” about the nature of, risk of, or alternatives to your product' and 'Report just the (impressive) relative risk reduction while suppressing the (unimpressive) absolute risk reduction and number needed to treat.'

lapis_exilis said...

@cavenewt - LOL!!!! the HARLOT plc thing is great πŸ‘πŸ» πŸ˜‚πŸ€“

cavenewt said...
This comment has been removed by the author.
cavenewt said...

Yes, the HARLOT proposal is very funny. And then you realize it's almost a perfect business plan for what the pharmaceutical companies have been doing for years.

Which is, of course, why the two (actually three) authors wrote it, as they had been intimately adjacent to such behavior for years.

Laugh and cry.

Peter said...

Hi Basti, yes, 25% pure fructose in the diet is undoubtedly a "model" and was clearly designed with a set of histo images in mind. I doubt it reflects reality in either species. I’m also very, very aware that in rodent models adding sucrose to a low fat diet at 37% of calories, just under a fifth of calories as fructose, simply activates FGF21, activates BAT and produces a slim insulin sensitive phenotype (perhaps I should say a phenotype of *normal* insulin sensitivity).

But it certainly looks like 10% of calories as sucrose, obviously 5% as fructose, appears to be a key component to the Surwit diet. My feeling is that fructose as a problem is probably very context specific.

Tucker, lots to work through there. I keep getting pulled back to peripheral cellular responses which I expect the brain to “model” in the hypothalamus as part of energy availability assessment. Looking at endocannabinoids such as 2-AG, with its parallel effects on adipocytes and CNS, is quite simple to interpret. Fructose is not in any way as intuitive. I need to work through your refs from this perspective…

cave, I really enjoyed the HARLOT paper, might have first read it a few years ago (via Malcom Kendrick?) and it’s nice to have a reminder.

Peter

davemoriarty2 said...

Unless I'm misunderstanding something, the takeaway from these papers seems to be that people shouldn't eat coconut oil. On a coconut oil diet, anything above 1% LA seems to be a problem, even without fructose. Sugar makes it worse. So (assuming this translates to humans), if you're eating a lot of coconut oil, you better not eat basically any LA or sugar at all, which is incredibly difficult.

If anything, the high starch basic chow is the one to beat so far, assuming it's low enough in everything else (definitely low in coconut oil, not sure how low in LA and sugar it has to be).

Also, these papers might be of interest, either in endorsing their conclusions or debunking them:

https://www.nature.com/articles/s41575-021-00472-y

Here's a link to some twitter commentary:

https://twitter.com/ArsenaultBenoit/status/1574323891727745024?s=20&t=yrgRVfs1JwifZN-uLF0Mxg