From: "Paul Ernsberger, Ph.D." <pre@po.cwru.edu>
Cc: jef8@arthur.INS.CWRU.Edu, rjk13@arthur.INS.CWRU.Edu,
dmb4@arthur.INS.CWRU.Edu
Heinz and ISMNT list:
Very interesting results! As you know, we are doing some similar
experiments, but with hypertensive and hypertensive and obese rats.
>
>> Sorry for the delay, but we just finished a series of rat experiments
>> where we examined changes in calorie intake and blood pressure (measured
>> by radio telemetry in conscious animals) after feeding (each for 2 weeks)
>> diets differing in fat content (8, 16, 24% coconut fat; wt/wt) and sucrose
>> content (16%, 32%, 50%; each on top of 24% fat).
>
>
>>>What made up the rest of the feed?
>
>It was a simple approach. Fat or sucrose was just added on a wt/wt basis to
>a powdered regular rat chow.
>
We used the AIN76 diet, which is a 60% sucrose purified diet.
>
>> The intriguing finding was that increasing the fat content had no effect
>> on calorie intake or blood pressure. However, adding sucrose (even 16%) to
>> the 24% fat diet resulted in an increased calorie intake and blood
>> pressure. Under these conditions, blood glucose was unchanged but insulin
>> was slightly (but significantly) increased. One might argue that the
>> increased insulin stimulates sympathetic activity which could account for
>> the increased blood pressure.
>
We also see a rise in blood rpessure by tail cuff (10-20 mmHg). There is
some impairment of glucose tolerance in a challenge test, but no effect on
fasting glucose.
We are concerned because some other groups have reported severe
hyperglycemia in obese rats fed sucrose (i.e. 500 mg/dl; see
http://www.gmi.com, for example).
>>>How did you measure calorie intake?
>
>
>Calorie intake was calculated from the daily food intake and the calorie
>content of the various diet constituents. The calculations seem to be close
>to reality since a calculated increased caloric intake was associated with a
>gain in body weight.
>
We found an increase in apparent caloric intake, but absolutely no change in
body weight relative to a control group fed regular chow.
>> One question comes up, however, immediately. Did the addition of sucrose
>> just make the food tastier and the rats consumed, therefore, more
>> calories which then increased sympathetic activity and blood pressure?
>> By contrast, one could speculate that sucrose increased insulin levels
>> specifically and thereby calorie intake.
>
>>>Coconut fat and sucrose make a terrific tasting diet. I wonder if you would
>>>find the same results with a tasteless margarine as your fat source and
>>>unsweetened bread as your carbohydrate?
>
>This is a good point. We actually repeated some of these experiments and
>exchanged coconut fat for linseed oil (again 24%). The idea was to see
>whether the n-6/n-3 ratio (linseed oil is high in the n-3 linolenic acid)
>has any effect, particularly on the rise in blood pressure. We were
>surprised not to see any difference. Your suggestion on the
>margarine/unsweetened bread diet needs to be done.
>
Not by us! Too messy!
>
>
>>>One difficulty in commenting on the theory is understanding the other
>>>components of the diet, that is, what was displaced by the added sucrose?
>>>Because sucrose is half glucose, it might stimulate a stronger insulin
>>>response than other types of carbohydrates in the baseline diet.
>
>
>We used a regular rat chow which contains mostly complex carbohydrates as
>sugar. So we increased the intake of simple sugars.
>
>>>Also, if your rats are still alive, I wonder if you have "reversed" the
>>>experiment to take out any cumulative effect of consuming highly saturated
>>>coconut fats. If the rats' arteries are becoming clogged due to the high
>>>saturated fat intake, might that not progressively affect blood pressure?
Rats do not get atherosclerosis. Eve our rats, which have elevated
triglycerides and cholesterol, do not get hardening of the arteries.
>>>Perhaps you have taken this into account and switched them back to the
>>>no-sucrose diet to see if their blood pressure fell again.
>
>A very good point. Actually after feeding 50% sucrose (for comparison with
>the often used high sucrose/fructose diets), we switched back to regular
>diet and blood pressure fell. Also the linseed oil data argue against some
>specific effect of saturated fat.
>
>> These experiments have some implications for the often discussed
>> socalled high protein diets. If calorie intake is shifted from
>> carbohydrate to protein in human, could this simply mean that the taste
>> is affected in a negative manner and thus calorie intake is reduced? Or
>> do we necessarily have to assume that insulin levels are specifically
>> reduced when carbohydrate intake is lowered?
>
>>>I have read comments by former adherents of the Atkins diet (high protein/
>>>extremely low carbohydrate) that a big plate of steak and eggs every
>>>morning quickly loses its appeal...but I don't know whether it also is a
>>>_low calorie_ diet. The Zone diet is not a high protein/low carbohydrate
>>>diet, but for many people it would shift some carbohydrate intake to
>>>protein intake. Reduced calorie intake in the Zone diet is enforced by
>>>substituting less carbohydrate-dense whole fruits and vegetables for more
>>>carbohydrate rich breads, pastas, rice cakes, etc., which is more filling,
>>>and adding monounsaturated fats to create the sensation of fullness.
>
>I agree that rat experiments have there definite limitations, but
>nonetheless we were intrigued to see that a most probably tasty diet is
>associated with a parallel increase in caloric intake, rise in blood
>pressure, blood insulin (and most probably sympathetic activity). Somehow I
>have the feeling that this situation matches the syndrome X (or metabolic
>syndrome) often encountered in overweight humans. Maybe I am going too far
>in speculation?
I think this is a very good model for human Syndrome X!
>
>
>> Since I am intrigued by these findings, I would be very grateful if I
>> could get some ideas on possibly underlying mechanisms.
>
>> Thank you
>
>> Heinz Rupp, PhD
>> Division of Cardiology
>> University of Marburg
>
I think we can rule out involvement of leptin. Our rats have a nonsense
mutation in their leptin receptor, but they still show a 10-20 mmHg increase
on high sucrose (very preliminary results, byu the way).
Paul Ernsberger, Ph.D., Associate Professor of Medicine, Pharmacology and
Neuroscience
Case Western Reserve School of Medicine, 10900 Euclid Ave., Cleveland, OH
44106-4982
Email: pre@po.cwru.edu FAX: (216) 368-4752
Visit the Imidazoline Receptor Web page at
http://www/mmcc.monash.edu.au/phimr/ireceptor