Chicken fillets are not meat. If you're a cat.

I've just had a very near miss with feeding one of my cats.

Mini came to us as a kitten around 2012. Back in those days I fed raw meaty bones and the only food available with bone sizes appropriate for a cat easily available in the UK was chicken wings. During bone growth I wanted to ensure adequate calcium and phosphate and nutritional grade bone meal had gone from routine use to virtually unavailable. I'd not, at that time, delved deep in to the problems of PUFA which are plentiful in the chicken wings.

Over the years she had low grade on-going gingivitis problems, with hindsight probably related to the high linoleic acid content of her diet. As I  came to realise that the omega 6 PUFA are a problem I transitioned most of our other cats to 12% fat beef mince and that's what they all eat nowadays.

Not Mini. She routinely threw up on beef mince but was fine on the chicken wings, so there she stayed.

Then she broke two teeth (on a chicken wing!) and when I did her dentistry it was obvious that her low grade gingivitis was not low grade and that all of her teeth were in a bad way, so I took them all out.

No cat is going to eat raw chicken wings with her gums. I tried her on beef mince again, she threw up again. Eventually I decided to try her on chicken breast meat, well cut up and relatively low in fat so low in PUFA. She liked it, maintained weight and had no suggestion of ammonia toxicity from an almost all protein diet. She's a cat after all.

Then last November she hid up under one of the children's beds and when I managed to get her out she was very distressed and had laboured breathing. A quick trip to the practice and 30 seconds of ultrasound by someone better at it than me confirmed heart failure.

Heart failure in cats is common. It's usually hypertrophic cardiomyopathy and is essentially untreatable. I assumed that if HCM was present then high protein + high glucose (cats really do convert protein to glucose continuously) -> high GH -> IGF-1 -> cardiac hypertrophy. Probably wrong but who knows? My colleague of the ultrasound machine was uncertain if she could see hypertrophic or dilated cardiomyopathy so I booked a scan with a cardiologist. A few frusemide tablets stopped her drowning and she had no suggestion of a thrombus or pre-thrombus in either atrium.

It was dilated cardiomyopathy. Or end stage hypertrophic cardiomyopathy where replacement of cardiac myocytes with fibrous tissue looks, on ultrasound, just like the dilated form.

DCM is genetic or caused by taurine deficiency. So I PubMed-ed:

The taurine content of common foodstuffs

and found this:

Poultry breast meat is special when compared to poultry leg/wing meat. It has the lowest taurine content of any meat. If you feed your cat on chicken fillets she will develop dilated cardiomyopathy. If the cardiomyopathy allows the generation of an atrial thrombus which breaks off the syndrome produced (iliac thrombosis) is terminal, whatever hope your vet might cautiously suggest re "treatment".

On the plus side DCM from taurine deficiency is completely reversible. Mini was re-scanned recently by the same cardiologist and now has a normal heart. She has been off of frusemide for months.

Taurine comes by the kilo as a sports supplement. I put a pinch of it on her food each night.

Due to my initial thoughts before getting the diagnosis I'd changed her on to beef mince yet again and was going to put up with paddling in cat vomit on the kitchen floor occasionally. Didn't happen. No more vomiting on beef. Huh?

So now all of our cats are on beef mince.

Moral of the story:

Don't feed you cat on chicken fillets.

That was a very, very near miss and (another) lesson to me that I do not have all of the answers! Occasionally reality bites you.

Peter

Addendum. There is a similar known problem with feeding whole ground rabbit carcasses to cats (of which I was aware, but had missed the selective taurine deficiency in white poultry meat):

Rabbit Carcasses for Use in Feline Diets: Amino Acid Concentrations in Fresh and Frozen Carcasses With and Without Gastrointestinal Tracts

Fructose (10) A can of cola

At some stage we have to transition from "fructose is good, it increases glycogen storage in the liver" through "if fructose is storing glycogen in the liver you can be damned sure it's storing lipid" through to "it causes hepatic insulin resistance" and the follow-ons from there.

This next study is pretty well supported by an established base of in-vivo and end-of-vivo studies which I think I can safely pass by and look at the induction in changes to insulin signalling, which might be interesting

Fructose Selectively Modulates c-jun N-Terminal Kinase Activity and Insulin Signaling in Rat Primary Hepatocytes

We're looking at this:

Aside: c-jun N-terminal kinase is what we expect to kill cells severely injured by being cultured in "fasting" levels of unadulterated palmitate plus glucose at 25mmol/l for 24 hours. You know the studies. Assume intolerable ROS. End aside.

The basic message from the paper is this:

The interesting parts of the paper allow us to ask hepatocytes very, very carefully, about the level of fructose exposure which inhibits insulin signalling. We can accept JNK activation as a crucial messaging step in converting fructose exposure to insulin resistance. The concept that this might be ROS driven is my own rather than anything in the paper per se.

This is the bar chart:

This model used steady state fructose exposure over four hours and is quite convincing that there is a "switch" somewhere between 0.4mmol/l and 0.6mmol/l. Our previous steady state study was that of dogs using fructose at 2.22 micromol/kg/min and this achieved a portal vein fructose of 0.1mmol/l:

Inclusion of low amounts of fructose with an intraduodenal glucose load markedly reduces postprandial hyperglycemia and hyperinsulinemia in the conscious dog

We can combine the data from both studies and suggest that, in summary, exposing hepatocytes to fructose a 0.1mmol/l is insulin signal augmenting and exposing them to fructose at 0.6mmol/l induces insulin resistance.

It is also perfectly reasonable to assume that the level of ROS which indicate that is a necessary time to induce insulin resistance are converted to a signal to be carried by the JNK pathway, exactly the one which carries the mitochondrial ROS indicator that it is necessary to induce insulin resistance.

Whether the pre-emptive signal generated by palmitic acid even at low delta psi is the same one as is generated by simple caloric overload (ie failure to resist insulin in time, ie linoleic acid) remains to be seen (by me at least, so far).

We can summarise that nibbling an apple might augment storage of a bowl of porridge as hepatic glycogen but downing two cans of fructose sweetened soft drink might do other things, not least of which is to induce hepatic insulin resistance.

Looking at things fundamentally, this is a story told by ROS signalling. All the signals downstream are certainly interesting and complex but tell us little about the underlying essential process, the information derived from which they are carrying and refining.

Peter

Fructose (09) The Surwit hepatocyte

I hope everyone has forgotten this diagram

which I simplified to this:

Well, now it's time to butcher it further, to an even simpler diagram:

And now I can get rid of the background faint image and shift things around a little to make some more space. I've also converted all "carbohydrate" pathways to blue.

which leaves room to add in mitochondrial, saturated fat derived ROS, the physiological antagonist to the ROS signal which we name as the "insulin" response, though insulin is but a partial contributor to the genuine ROS signal. We can show the blockade like this:

All very simple. Now lets look at the Surwit diet, 59% fat calories, mostly coconut oil, very low PUFA (~2% LA) and modest fructose (~6% of calories).

Aside. Oooh, look, the Surwit diet provides something very close to the 5% of calories as fructose which was used to augment glycogen formation in dogs. Neat. End aside.

I was going to get in to a deep morass at this point about why MCTs fail to generate an ROS signal in proportion to their chain length and degree of saturation. The aside became progressively larger and, not unexpectedly, more theoretical. For the sake of the discussion of the Surwit diet we just have to accept that coconut oil contains fatty acids which are dealt with differently to longer chain fatty acids and which generate a limited ROS signal.

So let's go back to the Surwit diet, 59% fat, mostly coconut, 13% sucrose, some maltodextrin and some casein.

First, at 6% fructose this will produce an insulin-augmenting level of ROS generation, solid blue arrow below. Next is the glucose from the sucrose and maltodextrin, generating a fairly low level of ROS, mostly via the insulin receptor, shown as a thin arrow because this diet is almost a low carbohydrate diet. Both the above generate ROS which signal "insulin" activation "downstream".

Next let's add in octanoate. For whatever reason this is a poor generator of ROS under physiological levels of exposure. It will do nothing to inhibit the "insulin" effector actions of the carbohydrate generated ROS:

I suppose you could even make a case that the relatively minor production of ROS from octanoate might actually produce an activation signal for the "insulin" effect. A possible explanation for this paper. Then you're really in trouble.

Or at least your liver is.

During the earlier posts on this thread about the actions of fructose I've cited papers which suggest that fructose derived ROS augment the formation of glycogen within hepatocytes. Very clever people are very welcome to look at which substrates change in which direction activating which enzyme pathways to generate this glycogen. It's complex.

To me it's much simpler. Augmented low level ROS -> "do what insulin does". One effect being glycogen accumulation.

In a Surwit type diet the directly supplied fatty acids are heavily slanted towards medium chain fatty acids. Mammals do not use MCTs for bulk caloric storage, the preference is toward a mix of palmitate +/- oleate. The liver is quite capable of converting caprylate to palmitate +/- oleate. In fact MCTs are segregated away from chylomicrons by the enterocytes in the gut and are diverted, as free fatty acids, to the portal vein and so directly to the liver for this to happen.

Given augmented hepatocyte insulin signalling combined with augmented access to free fatty acids, what is the likely effect of augmented "insulin cascade activating" ROS levels?

Could that be the accumulation of lipid in the cells subject to this combination of circumstances?

We call this fatty liver.

That's the first step of several.

Peter

Fructose (08) Acipimox and FFAs

Just a tidy up post. I got bored with acipimox. This is why inhibiting lipolysis using acipimox doesn't make you fat.

Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes

I've taken this from the top left panel of Fig 1 and removed the "day three" line so we just have the pre acipimox treatment solid line and the 28 day dashed line. I've added in red arrows to mark the acipimox dose times. Across the bottom are clock times for 24 hours:

It should come as no surprise that the AUC for FFAs on day 28 is virtually the same as that for pre treatment.

Whether this is a simple drug withdrawal effect or an effect mediated via increased size of already distended adipocytes ramping up basal lipolysis in the aftermath of being stretched by acipimox is hard to say, but the bottom line is it won't make you fat.

The beauty of linoleic acid as an obesogen is that it's there all the time from diet or released from lipid stores. All it needs is a decent level of carbohydrate induced insulin signalling for it to accentuate and you're away.

Under hypoinsulinaemia linoleic acid becomes (almost) powerless to augment insulin signalling because there's not much insulin there. Hence the efficacy of the low carbohydrate diet.

Should get back to fructose next.

Peter

Fructose (07) Acipimox tangent II

Acipimox is a drug which keeps on giving. Before I get back to fructose thoughts there's this post and maybe another given over to acipimox.

This is the current paper of interest:

Overnight Lowering of Free Fatty Acids With Acipimox Improves Insulin Resistance and Glucose Tolerance in Obese Diabetic and Nondiabetic Subjects

It has good points and bad points. The worst is the fact that the figures are of such low resolution as to be illegible in places, especially numerical scales to graphs.

On the plus side the tables are fine and the data extraordinarily confirmatory to my biases. Today I'm just looking at the "normal" slim people.

Here is the effect of acipimox on HOMA-IR from an on-line calculator using numbers from the slim, non-diabetic group:

Despite these subjects not supposedly having impaired glucose tolerance the HOMA-IR score derived from their mean fasting values is >2.0 suggesting some degree of insulin resistance. It's not easy to be healthy even as a slim 40 year old in Brazil.

This is easily corrected by acipimox giving an HOMA-IR score of 1.13, well under the cut off for IR.

It does this by locking fatty acids in to adipocyte triglyceride droplets and keeping them there. This, fundamentally, is what acipimox does. It locks lipids in to adipocytes.

From the ROS point of view there is then minimal fatty acid oxidation, minimal superoxide produced by reverse electron transfer through complex I, minimal inhibition of the insulin cascade at the level of insulin receptor substrate so maximal insulin signalling. The end result, in the basal state, shows as increased glucose oxidation and decreased fat oxidation:

These changes are absolutely secondary to the suppression of lipolysis by acipimox at the level of the adipocytes.

I hope all of this is starting to sound familiar.

I can't get this table out of my head

taken from here:

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

Acipimox is reproducing both the low HOMA-IR score and reduced lipid oxidation seen in slim people who are destined to become obese. Ignore the comment about genetics at the end of the abstract. People with obese parents are going to become obese themselves via the action of linoleic acid locking triglycerides in to adipocytes.

Before obesity develops they have "excellent" insulin sensitivity because they are metabolically hypocaloric due to concurrently starting becoming obese via lipid *loss/sequestration* in to adipocytes. They will have to eat more [carbohydrate] to make up their metabolic needs by however much lipid is sequestered in to their adipocytes. They will only become insulin resistant once those adipocytes become large enough that lipolysis cannot be adequately suppressed by insulin.

Acipimox recapitulates linoleic acid's insulin sensitising and obesogenic effects, but only for 6 hours at a time.

Linoleic acid accumulates in your adipose stores (and deep fat fryer) and is available continuously for years making you hypocaloric [ie hungry], especially when you avoid saturated fat. As cardiologists have advised for decades.

Of course, if you took acipimox every 6 hours for the rest of your life you would get fat, wouldn't you? I only discovered acipimox in pre-Protons days when I worked from the simplistic, partially correct idea that insulin inhibits lipolysis to make you fat. Pubmed "lipolysis" "inhibitor" "obesity" and acipimox pops out.

BTW It doesn't make you fat. Basal lipolysis was another gift of acipimox.

Peter