Thursday 13 June 2013

What is "Fat-mobilizing substance" ???

In reference to the mysterious hormone Kekwick and Pawan talked about in their 1960's era papers. Seriously, does anyone know what this is?

Best & Campbell in 1936 spoke of a substance isolated from the pituitary that would cause liver fat accumulation during fasting, while simultaneously decreasing fat contents of the fat depots ( i.e. bodyfat ).In 1947 Weil et al also confirmed the presence of a "fat mobilizing agent" isolated from the urine of a fasting rabbit, but not the normally fed rabbit.

They describe how injection of this substance caused an accumulation of liver fat at the expense of bodyfat,

A more detailed paper from Kekwick and Pawan 1960 actually goes on to describe a procedure of exactly how this substance can be isolated and extracted from the urine of fasted or carbohydrate restricted humans/animals. Upon injection of this substance, liver fat, blood lipids, and ketones all increase. Surprisingly this substance is also effective at lowering blood sugar. Furthermore, no changes in appetite or food intake accompanies this increased utilization of bodyfat from the injection of this substance.

So in essence, this substance either just straight up increases energy expenditure and/or reduces energy harvest from metabolic fuels.


Below are graphs of bodyweight of mice following injection of this substance, the substance produces a decrease in bodyweight without any significant changes in food intake.



Here is a graph when the injections are stopped after 10 days, NOTE the rapid return of bodyweight?


In the study they confirm the substance is not Corticotrophin, or Growth hormone, although it has similarities with these.

So the question is, what is this substance? Does anyone else know more about it? Has it since been proven to be a hoax?

I and others have commented on how extreme carbohydrate restriction in particular seems to produce rapid loss of bodyfat, and I cant help but wonder that in addition to reduced insulin, that this mysterious substance is also playing a role. The most shocking point is above in Fig 3, I.E. the rapid return of bodyweight after injections cease without changes in food intake. This sounds eerily like the rebound weight gain people experience after a period of lowcarbing when they try to re-introduce carbs into their diet. A re-introduction of carbs according to Kekwick and Pawan's research would shutdown production of this fat-mobilizing substance, and potentially make your regain weight, as in Fig3. with no changes in energy intake.

Thanks to Bill, I was able to get hold of the 1964 study  by Kekwick and Pawan that looked at high-fat diets in mice, at 50% calorie restriction, an 80% fat diet produced substantially more fat loss than a 80% carbohydrate diet, Kekwick and Pawan noted increased excretion of energetic metabolites on the 80% fat diet in the urine including Pyruvic acid, citric acid, and lactic acid. In general they report that urinary carbon increases in response to carbohydrate restriction, I.E. "wasting of energy".

Where fat supplies the major part of an energy deficient diet, there appears to be no attempt to utilize the diminished calorie intake more effectively in terms of supplying the organism with energy. It must therefore provide the whole of the deficiency from its own fat stores. \Vhen carbohydrate supplies the main part of a calorie deficient diet, the organism appears able to utilize the energy to better advantage and the deficiency required to be supplied from its own fat stores is less. On energy deficient diets of equal calorie value the animals are likely therefore to lose weight more rapidly when the calories are supplied in the form of fat than when they are supplied in the form of carbohydrates

One of their ideas for the increased fat loss on the high-fat diet is again the increase in this "fat-mobilizing substance" which is turn causes increased excretion of energetic metabolites in the urine.

So please, maybe someone can chime in here? Is this "fat mobilizing substance" bogus? IS there more to lowcarbing than simply a reduction in insulin?










13 comments:

  1. Beta-Lipotropin comes to mind. It is produced in the pituitary and has something to do with lipolysis, but I never looked into it and the wikipedia article is very short: http://en.wikipedia.org/wiki/Lipotropin

    ReplyDelete
  2. Could be!, although the wiki entry says lipotropin produces steroidogenesis but Kekwick and Pawan say

    "However, it is not identical with corticotrophin, since it exhibits none of the usual steroid-like effects in the intact animal, has only very low activity in releasing steroids from viable adrenal tissue, and after inactivation by hydrogen peroxide cannot be reactivated with cysteine."

    ReplyDelete
    Replies
    1. Oh well. I'll read the paper, maybe something else will come to mind..

      Delete
  3. I also forgot to mention that Kekwick and Pawan say that fat-mobilizing substance is de-activated by trypsin so you cannot drink your own urine to recycle this fat burner.

    ReplyDelete
    Replies
    1. Oh no. I was hoping for a business opportunity.

      Wait! What if you, hm, well, administer it another way?

      Delete
  4. It is lipolytic in rabbits: http://www.ncbi.nlm.nih.gov/pubmed/2210032
    and increases ketogenesis: http://www.ncbi.nlm.nih.gov/pubmed/6717761

    Here is a strange abstract on the hormone and food motivation: http://www.ncbi.nlm.nih.gov/pubmed/7326405

    A quick search revealed nothing about blood sugar though, let alone lipotropin injections..

    ReplyDelete
  5. could it be the FIAF that Peter describes?

    ReplyDelete
    Replies
    1. Wasnt that one secreted by the gut? This one is reported to be of pituitary origin,

      Strangely a pubmed search for beta lipotropin lists some of the older studies by kekwick and pawan which is rather strange, since I dont think they ever actually named it.

      Delete
    2. FIAF is made all over the place, mostly in the liver, WAT, and as Kindke said, the gut...

      Delete
  6. I wonder, if the lowering of blood sugar is not observe, does it indicate the absence of the mysterious substance? Dr. Eades claimed that his patients were loosing fat from livers.

    ReplyDelete
  7. Are we sure it's of pituitary origin? It seems possible that some product of the pituitary gland (some peptide or whatever from the pituitary encouraging secretion of some other substance elsewhere) is involved.

    http://joe.endocrinology-journals.org/content/180/3/R1.long

    "Food restriction regulates adipose-speciļ¬c cytokines in pituitary
    gland but not in hypothalamus"



    I know pretty much squat in this area--but it's possible that some sort of fiaf-involved central signal might be involved, affecting fiaf production and appearance elsewhere in the body.

    ReplyDelete
    Replies
    1. Im not sure of anything here myself tbh, it may not be of "pituitary origin", the only thing Kekwick and Pawan say is that a functioning pituitary was necessary for its presence in urine during fasting. And it is absent from urine in fasting with Hypopituitarism.

      Best & Campbell noted that it was present in certain extracts of the anterior pituitary gland which however does suggest it might be of pituitary origin.

      Delete
  8. Great post, Kindke.

    Reducing calories on a high carb diet improves metabolic efficiency, but reducing calories on a high fat diet doesn't affect metabolic efficiency. OK. This jives with some of the more recent energy balance studies (http://caloriesproper.com/?p=2352), although K&P attribute it to urinary carbon loss as opposed to energy expenditure? Interesting.

    ReplyDelete