Let's look this abstract. Thanks to Liz for the full text.
The key quote is, of course:
"In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications."
I'm not sure what the word for a collection of idjuts is. A moronity?
Despite this the data are very interesting.
Look at those hepatic diglycerides, up 350%!!!!!!
Failure to suppress hepatic glucose output. Not just reduced, but reduced to zero percent suppression. Zero percent!
Wow, are these mice gonna die of diabetes, fatty liver, metabolic syndrome, Spawn of Satan induced inflamasomation.... Okay, I'll calm down now.
These mice are running their metabolism on a combination of free fatty acids and ketone bodies. What would you expect their liver to be full of? Sugar?
Glycogen?
Maybe fatty acids?
Well, in ketosis FFAs come from transport by albumin or release by lipoprotein lipase as exactly that, free fatty acids. They are not stored in this form, they are re-esterified to triglycerides for hepatic storage. The 350% increase in diglycerides is not from being swamped with diglycerides exogenously. They are generated in situ specifically to stop the liver responding to insulin.
These mice have no source of dietary glucose. They are generating and outputting small amounts of glucose from their liver, despite extreme protein restriction, to keep their blood glucose levels compatible with life. Possibly from glycerol.
Then some joker comes along with an insulin infusion. What would happen if their ability to trickle out glucose actually did suppress in response to this malevolent tease? Death would ensue in a few minutes without a rescue glucose infusion as is needed for the mice on CIAB. Hepatic diglycerides are generated to stop the liver responding to insulin when survival makes this an absolute necessity. It's an absolute necessity under extreme ketosis conditions, even without the joker with a bottle of insulin.
To get a breath of KetoSanity we can go back to the paper by Maratos-Flier's group (thanks to John for the heads up on this "non conformist").
These folks didn't look at diglycerides but they did measured the liver triglycerides and found they were nearly twice those of the mice fed crapinabag. Gasp! Fatty liver is where it's at. But these folks did a little histopathology too, using PAS to stain for glycogen. As they say:
"PAS staining showed decreased glycogen deposition in KD animals vs. both HF- and C-fed groups (data not shown)"
If your liver is glycogen depleted what, exactly, should it have as an energy store? Thin air? A small nuclear reactor?
Maratos-Flier et al understand exactly what is going on and see no need to trot out hysteria about ketosis generating a fatty liver which is physiological. It has nothing to do with fatty liver under a carbohydrate based diet.
Now, what would happen if we increased the carbohydrate content of the diet to 15% of calories in the same way as Axen and Axen did in their 2006 blooper?
Ketosis would stop and hepatic insulin sensitivity would return. Probably within three days and certainly within the three weeks A & A allowed. The diglycerides would be gone. Probably so would the bulk of the triglycerides. Under these conditions carbohydrate would clear the fatty liver.
Would the mice be diabetic? You've got to be joking.
So why does carbohydrate restriction improve fatty liver in humans? I would suggest the lack of de novo lipogenesis due to fructose reduction coupled with chronically lowered insulin allowing VLDL output to clear the excess of hepatic triglycerides. The situation is completely different.
I doubt many LC dieters would push themselves to the ultra extreme of the diet enjoyed by these KD consuming mice. If they did, their hepatic lipids, especially diglycerides, would have to increase to produce an utterly essential survival gift of hepatic insulin resistance. Their hepatic triglycerides would rise too.
I think it's an open question about whether placing yourself at the very extremes of physiology is a good or a bad thing. It should certainly assist weight loss, but would it improve health? Interesting question.
Peter
Showing posts with label Mice. Show all posts
Showing posts with label Mice. Show all posts
Sunday, July 31, 2011
Saturday, July 30, 2011
LIRKO mice (1)
I think we have to look at the LIRKO mouse. This fascinating beastie was brought to my attention by Chris Masterjohn and it's hard to know where to start with how amazing these animals are.
I suppose the first thing that grabbed me is that they are alive at all. They have no insulin receptors on their liver. None. You don't actually need insulin receptors on your liver to be alive... OK, they're pretty sick and go in to early liver failure, but they're definitely alive and reasonably functional at four months of age.
They have fed-state plasma insulin levels TWENTY times higher than those of control mice and fasting insulin levels eight times higher than controls. They are the ultimate model of hyperinsulinaemia.
They are, err, slim. Slimmer than control mice. Now that is cool!
So we have mice with massive levels of insulin. If you took an average mouse and injected enough insulin to peak its blood concentration at 20 times the physiological level it would rapidly become an ex mouse. It would be a late mouse. It would be no longer. But that's not what's happening.
These mice are eating CIAB and their liver wants nothing to do with the diet derived glucose. Nothing. The liver is utterly insulin resistant. No receptors, no response...
The mice eat Mouse Diet 9F which is 56.5% carbohydrate. Each mouthful of food pushes glucose toward the liver. The liver ignores it. Unharvested glucose hits the systemic circulation. The pancreas notices. The pancreas whispers insulin in to the portal vein and the liver ignores it. The pancreas speaks louder. The liver ignores it. The pancreas screams. The liver shrugs.
Where does the glucose go? With a blood glucose of 400mg/dl some goes down the loo (did I mention these mice were intensely diabetic? OK, they are intensely diabetic). The rest of the glucose tries its damnedest to get in to muscles. The muscles really don't want the glucose. They internalise their insulin receptors. Did I mention that these mice are intensely insulin resistant. OK, they are. Very. Whole body). The pancreas breeds extra beta cells then goes to the gym and pumps up those beta cells to steely muscled bulges of insulin hypersecreting islets. Insulin secretion goes up yet higher. It does no good. Not only do the beta cells multiply and hypertrophy, don't forget that the liver is the main sump for insulin degradation on a high carbohydrate diet. Not without insulin receptors it isn't. Hepatic insulin clearance is zero so insulin has almost nowhere to go. This too markedly contributes to the hyperinsulinaemia.
It would be interesting to see quite how high insulin would go if there was not the urinary route out for glucose... The bilateral nephrectomised LIRKO mouse. There's an interesting ICU challenge!
Does this massive hyperinsulinaemia inhibit lipolysis? Well, yes it does.
Interestingly FFAs are only reduced by about 40% compared to the control mice. But they are reduced. So why don't these mice become obese?
Ultimately they don't become obese because they cut calories. They are ad lib fed, they must cut calories because they're not hungry. Gasp.
Let's talk leptin. And insulin, of course.
Peter
I suppose the first thing that grabbed me is that they are alive at all. They have no insulin receptors on their liver. None. You don't actually need insulin receptors on your liver to be alive... OK, they're pretty sick and go in to early liver failure, but they're definitely alive and reasonably functional at four months of age.
They have fed-state plasma insulin levels TWENTY times higher than those of control mice and fasting insulin levels eight times higher than controls. They are the ultimate model of hyperinsulinaemia.
They are, err, slim. Slimmer than control mice. Now that is cool!
So we have mice with massive levels of insulin. If you took an average mouse and injected enough insulin to peak its blood concentration at 20 times the physiological level it would rapidly become an ex mouse. It would be a late mouse. It would be no longer. But that's not what's happening.
These mice are eating CIAB and their liver wants nothing to do with the diet derived glucose. Nothing. The liver is utterly insulin resistant. No receptors, no response...
The mice eat Mouse Diet 9F which is 56.5% carbohydrate. Each mouthful of food pushes glucose toward the liver. The liver ignores it. Unharvested glucose hits the systemic circulation. The pancreas notices. The pancreas whispers insulin in to the portal vein and the liver ignores it. The pancreas speaks louder. The liver ignores it. The pancreas screams. The liver shrugs.
Where does the glucose go? With a blood glucose of 400mg/dl some goes down the loo (did I mention these mice were intensely diabetic? OK, they are intensely diabetic). The rest of the glucose tries its damnedest to get in to muscles. The muscles really don't want the glucose. They internalise their insulin receptors. Did I mention that these mice are intensely insulin resistant. OK, they are. Very. Whole body). The pancreas breeds extra beta cells then goes to the gym and pumps up those beta cells to steely muscled bulges of insulin hypersecreting islets. Insulin secretion goes up yet higher. It does no good. Not only do the beta cells multiply and hypertrophy, don't forget that the liver is the main sump for insulin degradation on a high carbohydrate diet. Not without insulin receptors it isn't. Hepatic insulin clearance is zero so insulin has almost nowhere to go. This too markedly contributes to the hyperinsulinaemia.
It would be interesting to see quite how high insulin would go if there was not the urinary route out for glucose... The bilateral nephrectomised LIRKO mouse. There's an interesting ICU challenge!
Does this massive hyperinsulinaemia inhibit lipolysis? Well, yes it does.
Interestingly FFAs are only reduced by about 40% compared to the control mice. But they are reduced. So why don't these mice become obese?
Ultimately they don't become obese because they cut calories. They are ad lib fed, they must cut calories because they're not hungry. Gasp.
Let's talk leptin. And insulin, of course.
Peter
LIRKO mice (2)
This post is a bit rushed so apologies for typos/grammar, but there is a just usable swell and low tide in First Bay is in just over an hour's time so the 'yak is on the car... Just need the Baba to wake up and we're off.
Here are the facts and figures for LIRKO mice from this paper:
OK, they really are slim, they have about 10% less bodyfat than control mice. Here are some of the biochemical details:
The LIRKO mouse has a leptin level which is 10 times that of a control mouse, despite having 10% less bodyfat, that's graph A. Does this mean it's fooling its brain in to thinking it is obese? Probably not, Graph B shows that LIRKO mice have almost infinitely more sOb-R in their blood. This is a binding protein for leptin, bound leptin is biologically inactive. In graph C we can see that free leptin per unit fat mass is actually very low.
Graphs D, E and F show hat happens when you infuse leptin or saline intravenously for 30 minutes. Note the log scales. Graph D shows it is possible to get leptin to equally astronomical levels in LIRKO or normal mice. Graph E shows that the leptin binding protein, sOb-R, doesn't change in the LIRKO mice but falls non significantly in normal mice on leptin infusion. Graph F shows that the free leptin index goes up significantly more for control mice than for LIRKO mice. ie the control mice should feel less hungry and so eat less
But that's not what happens. Four days of leptin injections drops appetite and weight more in LIRKO mice than in control mice. Despite the appetite suppressing free leptin index being higher in the controls.
This appears to happen because the brain of a LIRKO mouse is more leptin sensitive than that of a control mouse:
SOCS3 mRNA level is something I've not read about but I'm willing to accept that it is a marker of hypothalamic leptin resistance.
Does any of this mean anything? Yes.
The LIRKO mice have no hepatic insulin sensitivity because of a very specific genetic defect which deletes their liver insulin receptors.
The liver does not know this. As far as it is concerned the pancreas is simply not secreting any insulin, ie there is no food being eaten. There may be a ton of glucose floating past but, as far as the liver is concerned, there is none.
Are there any other conditions which mimic this and might also spike sOb-R? The paper cites three. Type 1 diabetes. Here there is a ton of glucose but zero insulin. Total insulin deficiency is "hepatically" indistinguishable from the LIRKO liver not seeing any of the insulin (or glucose) raging through the bloodstream. Low insulin in T1 diabetes. High sOb-R.
Anorexia nervosa produces a genuine combined insulin and caloric deficiency with a high level of sOb-R. Low insulin. High sOb-R.
Ditto a 72 hour fast in men. Low insulin. High sOb-R.
How about ketogenic dieting? Here too there is low insulin. Will blood leptin binding increase? Hypothalmic leptin sensitivity increase? Appetite be normal? While ketogenic dieted mice do not particularly drop their caloric intake they do, like type 1 diabetics, fail to increase their caloric intake to meet on going caloric output (they become warm rather than glycosuric as their caloric "sink")...
Now, where does the letpin binding sOb-R come from? The liver is the source in LIRKO mice. The LIRKO mice have liver cells which are in a starvation situation. They manipulate leptin binding and availability to keep appetite normal.
What controls sOb-R production in normal liver cells?
Insulin.
If you put normal liver cells in a petridish with insulin they reduce production of mRNA for the short leptin receptor gene which produces one of the sOb-Rs. Under zero insulin the mRNA level for the Ob-Ra gene is 5 times higher than under 0.1micromol of insulin. Leptin itself has some suppressive effect, but insulin is the dominant hormone.
This looks very much like the liver has a mechanism for controlling leptin sensitivity.
Insulin. Hmmmmmm
As a complete aside: The other potential mechanism for the decreased appetite is insulin per se. Now, we are all fully aware that insulin is anorexic agent. All you have to do is inject a little insulin in to your brain and you will decrease your appetite. This is logical, after a meal you have a high insulin level and shouldn't want to eat.
Under fasting conditions you have low insulin levels and should want to eat. It's likely to keep you alive. Simple.
So, to stop people being hungry, all we need is to inject insulin in to their brain. Overweight? There's the queue...
For those of us who wish to lose weight without that intra cerebral injection we could try mainlining insulin. This may or may not suppress appetite. I've never tried it. Certainly none of my hyperglycaemic patients seem hungry when I inject them with insulin by the subcutaneous route. Until their blood glucose level drops below about 6mmol/l that is.
At that point they will eat ANYTHING. And lick the bowl. I'm not sure if they feel guilty afterwards. None of them seem to go and make themselves vomit in private to stay slim. Difficult to hide the evidence in a ward cage!
But the LIRKO mouse, with insulin levels 8-20 times those of a control mouse, never becomes hypoglycaemic. It's ONLY hyperinsulinaemic BECAUSE it can't mop up dietary glucose.
So perhaps we are actually seeing the anorexic effect of insulin in this mouse model. The levels might be high enough. The paper wasn't set up to look at this, but it's an interesting afterthought. Back to leptin.
Finally, how does the hepatic insulin resistance of a LIRKO mouse compare to the hepatic insulin resistance of a sucrose fed mouse?
The sucrose mouse hepatocytes have insulin receptors. They can be made to respond. They prefer not to only because these hepatocytes are utterly stuffed with diet derived calories which they are converting to fat as fast as they can but can't export until insulin levels drop low enough to allow VLDL output. Which doesn't happen. Mmmm, Pâté de foie gras...
They are in a state of hypercaloric stuffedness, they see blood insulin and glucose and just don't want anything to do with either. Do they make a ton soluble of leptin binding receptor, sOb-R? No. In human obesity leptin is high, sOb-R is LOW and hypothalamic leptin resistance high.
Now, really finally, how does the LIRKO mouse type of liver insulin resistance compare to the hepatic insulin resistance of an extreme ketogenic fed mouse? It's exactly the same. Low insulin. So if you fed a LIRKO mouse an extreme ketogenic diet, would you "cure" its diabetes?
Probably yes.
If you based the ketogenic diet around butter rather than the almost pure PUFA in Mouse Diet 9F, would you prevent its cirrhosis? The liver is only getting its calories primarily from dietary fat after all.
Probably yes.
If you gave some LIRKO mice free choice of macronutrients ratio, would they put themselves on an extreme ketogenic diet to treat their diabetes? Of course they would. They're mice, they're not stupid.
Do I like the LIRKO mouse? Absolutely.
But the FIRKO mouse is even more interesting and paradoxical... Maybe another day.
Peter
Here are the facts and figures for LIRKO mice from this paper:
OK, they really are slim, they have about 10% less bodyfat than control mice. Here are some of the biochemical details:
The LIRKO mouse has a leptin level which is 10 times that of a control mouse, despite having 10% less bodyfat, that's graph A. Does this mean it's fooling its brain in to thinking it is obese? Probably not, Graph B shows that LIRKO mice have almost infinitely more sOb-R in their blood. This is a binding protein for leptin, bound leptin is biologically inactive. In graph C we can see that free leptin per unit fat mass is actually very low.
Graphs D, E and F show hat happens when you infuse leptin or saline intravenously for 30 minutes. Note the log scales. Graph D shows it is possible to get leptin to equally astronomical levels in LIRKO or normal mice. Graph E shows that the leptin binding protein, sOb-R, doesn't change in the LIRKO mice but falls non significantly in normal mice on leptin infusion. Graph F shows that the free leptin index goes up significantly more for control mice than for LIRKO mice. ie the control mice should feel less hungry and so eat less
But that's not what happens. Four days of leptin injections drops appetite and weight more in LIRKO mice than in control mice. Despite the appetite suppressing free leptin index being higher in the controls.
This appears to happen because the brain of a LIRKO mouse is more leptin sensitive than that of a control mouse:
SOCS3 mRNA level is something I've not read about but I'm willing to accept that it is a marker of hypothalamic leptin resistance.
Does any of this mean anything? Yes.
The LIRKO mice have no hepatic insulin sensitivity because of a very specific genetic defect which deletes their liver insulin receptors.
The liver does not know this. As far as it is concerned the pancreas is simply not secreting any insulin, ie there is no food being eaten. There may be a ton of glucose floating past but, as far as the liver is concerned, there is none.
Are there any other conditions which mimic this and might also spike sOb-R? The paper cites three. Type 1 diabetes. Here there is a ton of glucose but zero insulin. Total insulin deficiency is "hepatically" indistinguishable from the LIRKO liver not seeing any of the insulin (or glucose) raging through the bloodstream. Low insulin in T1 diabetes. High sOb-R.
Anorexia nervosa produces a genuine combined insulin and caloric deficiency with a high level of sOb-R. Low insulin. High sOb-R.
Ditto a 72 hour fast in men. Low insulin. High sOb-R.
How about ketogenic dieting? Here too there is low insulin. Will blood leptin binding increase? Hypothalmic leptin sensitivity increase? Appetite be normal? While ketogenic dieted mice do not particularly drop their caloric intake they do, like type 1 diabetics, fail to increase their caloric intake to meet on going caloric output (they become warm rather than glycosuric as their caloric "sink")...
Now, where does the letpin binding sOb-R come from? The liver is the source in LIRKO mice. The LIRKO mice have liver cells which are in a starvation situation. They manipulate leptin binding and availability to keep appetite normal.
What controls sOb-R production in normal liver cells?
Insulin.
If you put normal liver cells in a petridish with insulin they reduce production of mRNA for the short leptin receptor gene which produces one of the sOb-Rs. Under zero insulin the mRNA level for the Ob-Ra gene is 5 times higher than under 0.1micromol of insulin. Leptin itself has some suppressive effect, but insulin is the dominant hormone.
This looks very much like the liver has a mechanism for controlling leptin sensitivity.
Insulin. Hmmmmmm
As a complete aside: The other potential mechanism for the decreased appetite is insulin per se. Now, we are all fully aware that insulin is anorexic agent. All you have to do is inject a little insulin in to your brain and you will decrease your appetite. This is logical, after a meal you have a high insulin level and shouldn't want to eat.
Under fasting conditions you have low insulin levels and should want to eat. It's likely to keep you alive. Simple.
So, to stop people being hungry, all we need is to inject insulin in to their brain. Overweight? There's the queue...
For those of us who wish to lose weight without that intra cerebral injection we could try mainlining insulin. This may or may not suppress appetite. I've never tried it. Certainly none of my hyperglycaemic patients seem hungry when I inject them with insulin by the subcutaneous route. Until their blood glucose level drops below about 6mmol/l that is.
At that point they will eat ANYTHING. And lick the bowl. I'm not sure if they feel guilty afterwards. None of them seem to go and make themselves vomit in private to stay slim. Difficult to hide the evidence in a ward cage!
But the LIRKO mouse, with insulin levels 8-20 times those of a control mouse, never becomes hypoglycaemic. It's ONLY hyperinsulinaemic BECAUSE it can't mop up dietary glucose.
So perhaps we are actually seeing the anorexic effect of insulin in this mouse model. The levels might be high enough. The paper wasn't set up to look at this, but it's an interesting afterthought. Back to leptin.
Finally, how does the hepatic insulin resistance of a LIRKO mouse compare to the hepatic insulin resistance of a sucrose fed mouse?
The sucrose mouse hepatocytes have insulin receptors. They can be made to respond. They prefer not to only because these hepatocytes are utterly stuffed with diet derived calories which they are converting to fat as fast as they can but can't export until insulin levels drop low enough to allow VLDL output. Which doesn't happen. Mmmm, Pâté de foie gras...
They are in a state of hypercaloric stuffedness, they see blood insulin and glucose and just don't want anything to do with either. Do they make a ton soluble of leptin binding receptor, sOb-R? No. In human obesity leptin is high, sOb-R is LOW and hypothalamic leptin resistance high.
Now, really finally, how does the LIRKO mouse type of liver insulin resistance compare to the hepatic insulin resistance of an extreme ketogenic fed mouse? It's exactly the same. Low insulin. So if you fed a LIRKO mouse an extreme ketogenic diet, would you "cure" its diabetes?
Probably yes.
If you based the ketogenic diet around butter rather than the almost pure PUFA in Mouse Diet 9F, would you prevent its cirrhosis? The liver is only getting its calories primarily from dietary fat after all.
Probably yes.
If you gave some LIRKO mice free choice of macronutrients ratio, would they put themselves on an extreme ketogenic diet to treat their diabetes? Of course they would. They're mice, they're not stupid.
Do I like the LIRKO mouse? Absolutely.
But the FIRKO mouse is even more interesting and paradoxical... Maybe another day.
Peter
Mice and breast cancer
Laura and Elizabeth (thanks for full text) both forwarded links to this study.
Low carb diets, in the correct mouse model, delay onset and slow progression of breast cancer.
It says the sorts of things you would expect it to say and, if you really feel this highly artificial mouse model has relevance to the sorts of breast cancer humans might develop, it certainly suggests that a low carbohydrate diet might have some benefits. But the paper itself is awful.
Two giggles did come out of it. First was the use of high percentage of casein as the sole protein source. Now somewhere, sometime, there was a vegan nut who screamed that casein was carcinogenic. China? China Syndrome? China Study? T. Colon Campbell???? Shrug. These has-been vegans get everywhere.
The second is the extreme fat phobia of the authors. I know these people have to make a crust and funding is not what it used to be and fat bashing is always helpful but there eventually comes a point when people really believe that fat causes cancer. Even highly saturated milk fat.
You can just imagine that cows evolved casein and palmitic acid to kill their calves. Or humans are not mammals in the same way as cows are, human breasts having evolved to sell newspapers rather than to feed offspring. Human babies should be fed sucrose water with a little soya bean oil added of course. It's a strange world.
I have reached the point where I no longer give any credence to high fat diet studies where 30% of the calories are coming from sucrose or the pellets are stained red to signify Crisco. Not so the current authors.
Ultimately, while sucrose and trans fats are excellent substances to study when looking at the effects of pushing the profitability of the food industry to its absolute maximum, they have nothing to do with a high fat diet based on Food.
Reading through the full text there are so many failures of perception and basic biochemistry that it might be worth a post in the end, but here's a typical blooper. Not only do we have Gourmand rats, we also have mice who need false teeth!
First we have to have another black box warning
******************************************************************
Untested ad hoc hypotheses can make you look very stupid.
******************************************************************
Here we go:
"Although mice on 8% CHO diet had slower growing tumors, they lost weight, weighing, on average, 20% less than mice on 5058 diet (Fig. 1D). This was consistent with the mice eating less than the 5058 group (data not shown), likely because the 8% CHO pellets were significantly harder to chew."
Executive summary: We're idiots.
Extended translation:
Diet 5058 is standard breeding colony crap-in-a-bag with 55% of calories from starch. It appears to be mildly obesogenic compared to 8% of calories from starch... That MUST be because the lower carb diet is too hard to chew. We couldn't be arsed to have a control group offered a harder diet with 55% carbs because we're idiots, as are our scrutineers.
GCBC anyone?
Oh, and another giggle: 5058 is described, COMPLETELY incorrectly, as a "Western Diet". It's a starch based, sucrose free, 20% fat, mostly PUFA, trans free diet, remarkably similar to Barnard's idiotic vegan diet for the progression of diabetes in humans. It's standard mouse chow.
Where do funding bodies find these people to throw their money at?
Eeeh, yer has ter larph.
Peter
Low carb diets, in the correct mouse model, delay onset and slow progression of breast cancer.
It says the sorts of things you would expect it to say and, if you really feel this highly artificial mouse model has relevance to the sorts of breast cancer humans might develop, it certainly suggests that a low carbohydrate diet might have some benefits. But the paper itself is awful.
Two giggles did come out of it. First was the use of high percentage of casein as the sole protein source. Now somewhere, sometime, there was a vegan nut who screamed that casein was carcinogenic. China? China Syndrome? China Study? T. Colon Campbell???? Shrug. These has-been vegans get everywhere.
The second is the extreme fat phobia of the authors. I know these people have to make a crust and funding is not what it used to be and fat bashing is always helpful but there eventually comes a point when people really believe that fat causes cancer. Even highly saturated milk fat.
You can just imagine that cows evolved casein and palmitic acid to kill their calves. Or humans are not mammals in the same way as cows are, human breasts having evolved to sell newspapers rather than to feed offspring. Human babies should be fed sucrose water with a little soya bean oil added of course. It's a strange world.
I have reached the point where I no longer give any credence to high fat diet studies where 30% of the calories are coming from sucrose or the pellets are stained red to signify Crisco. Not so the current authors.
Ultimately, while sucrose and trans fats are excellent substances to study when looking at the effects of pushing the profitability of the food industry to its absolute maximum, they have nothing to do with a high fat diet based on Food.
Reading through the full text there are so many failures of perception and basic biochemistry that it might be worth a post in the end, but here's a typical blooper. Not only do we have Gourmand rats, we also have mice who need false teeth!
First we have to have another black box warning
******************************************************************
Untested ad hoc hypotheses can make you look very stupid.
******************************************************************
Here we go:
"Although mice on 8% CHO diet had slower growing tumors, they lost weight, weighing, on average, 20% less than mice on 5058 diet (Fig. 1D). This was consistent with the mice eating less than the 5058 group (data not shown), likely because the 8% CHO pellets were significantly harder to chew."
Executive summary: We're idiots.
Extended translation:
Diet 5058 is standard breeding colony crap-in-a-bag with 55% of calories from starch. It appears to be mildly obesogenic compared to 8% of calories from starch... That MUST be because the lower carb diet is too hard to chew. We couldn't be arsed to have a control group offered a harder diet with 55% carbs because we're idiots, as are our scrutineers.
GCBC anyone?
Oh, and another giggle: 5058 is described, COMPLETELY incorrectly, as a "Western Diet". It's a starch based, sucrose free, 20% fat, mostly PUFA, trans free diet, remarkably similar to Barnard's idiotic vegan diet for the progression of diabetes in humans. It's standard mouse chow.
Where do funding bodies find these people to throw their money at?
Eeeh, yer has ter larph.
Peter
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