Sunday, 14 July 2013

Delta-sleep inducing peptide - FAIL?

In my on-going effort to mitigate the affects of my shift work and improve my sleep, I tried the injectable version of delta-sleep inducing peptide. Took 100mcg in the afternoon via subcutaneous injection in the belly, through an insulin needle.

I felt quite sleepy for about 2 hours after, then went back to normal. delta-sleep inducing peptide ( DSIP ) is suppose to help sleep, and especially improve slow-wave sleep. according to the literature, it doesn't matter what time of you day you take it, and its affects supposedly last for a few days after 1 injection.

Anyway, the morning after my first shot I felt quite groggy and had the classic fatigue that is associated with severely reduced REM sleep. I know when I have had reduced REM sleep because my thinking is slow and lazy, motivation to do anything is low as is general energy levels. Well so, DSIP has been a FAIL on the first night.

some info on DSIP can be found here

Friday, 12 July 2013

Melanotan II

Ive found a reputable UK source for melanotan II so im about to order some and give it a try, I am skin type 1 which means I NEVER tan naturally and only burn and peel.

Melanotan is a synthetic analogue of α-MSH, it has some side affects including increased libido and reduction in appetite. So it "may" be slightly helping for weight loss aswell. Melanotan II is also an mc4r agonist which is probably where it mediates the reduced appetite and libido side affects.


An interesting video on trenbolone, what I like is the fact this guy has done the research and there are some interesting points, he explains all the in the video.

of note, his research again supports the idea of nutrient partitioning, trenbolone apparently causes massive insulin sensitivity in muscle, ( glut4 ) . This is as opposed to increased insulin sensitivity in adipose tissue, ( glut4 ), which causes fat gain.

So the point seems to be, where is the insulin sensitivity and in particular where is the glut4? That plays a big part in where your "calories" go. The same is also true for LPL. Skeletal muscle LPL protects against fat gain, while adipose LPL increases fat gain. ( link )

For the record, I dont agree with everything this guy says, im just sharing an interesting video.

Wednesday, 3 July 2013

Ketogenesis, & Calorie restriction increases fatty acid synthesis

Malonyl-CoA: the regulator of fatty acid synthesis and oxidation

This is a short paper on ketogenesis and is well wroth a read imo. Very accessible even to the layperson. Interestingly, the ketone acetoacetate is the preferred substrate for fuel, chosen above even glucose. The liver is the only place ketones are synthesized, and the liver itself cannot oxidize ketones, it can only release them.

I was one of the people who thought that the switch for ketogenesis was simply the depletion of oxaloacetate in the liver mitochondria, but this is not true. Apparently the signal for ketogenesis is glucagon, aswell as a decrease in Malonyl-CoA in the liver. Once the glucagon signal hits the liver, the rate-limiting step for ketogenesis is simply the amount of fats reaching the liver from the adipose tissue. The liver will burn fats and generate ketones as fast as it can.

Anyway, just read the paper. !

Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates

This is another fascinating paper, I havent seen it discussed elsewhere, if memory serves.....

The paper is another fantastic demonstration of the futility of calorie restriction in attempting to lose weight. ( although that was not the objective of the study ). Mice subjected to 30% calorie restriction achieved a lower bodyweight,

After an initial 1- to 2-wk period of weight loss, CR mice reestablish a state of energy balance in which fat mass is preserved or even increased.

The paper talks about the nutrient balancing hypothesis, and that to remain weight stable, the food quotient must match the respiratory quotient. I.E. if you eat 300g carbs and 100g fats per day, then you must also oxidize 300g of carbs and 100g of fats per day to remain weight stable. If you burnt 150g of fat per day in that example, then the theory says you would lose fat mass.

So what happened in this study was that, the 30% calorie restricted mice were only allowed to eat 92mg of fat per day, but the researchers found the mice were oxidizing 367mg of fat per day.  Thats a calorie deficit of 275mg of fat per day, so the question was, why werent the mice losing weight? Why where they weight stable? They were in calorie deficit!

Well, the researchers found that the adipose tissue ( not the liver ) of the calorie restricted mice were actually synthesizing the missing 275mg of fat per day!.

In addition, in the first 3 h postfeeding, endogenously synthesized palmitate accumulated in the subcutaneous depot five times faster in calorie restricted mice than in ad-libitum controls,
Glucose is likely the predominant substrate for FA synthesis in the adipose tissue. Consistent with adipose playing a role in FA synthesis, Wetter et al. (45) demonstrated that glucose uptake is increased in adipose tissue of calorie-restricted rats.

And this...

 immediately after food was provided, fatty-acid synthase enzyme expression increased 50-fold in calorie restricted mice, leading to values nearly threefold higher than ad-libitum controls

Anyway, as I spoke of before, calorie restriction increases AgRP, this in turn blocks MC4R signalling. Maybe whats happening is that a lack of MC4R signalling in adipose tissue leads to elevated FA synthesis in white adipocytes? Well, even if this is not the mechanism, the point remains, 30% calorie restriction increases FA synthesis in your adipocytes.

But what about 20% calorie restriction? Maybe I can lose weight there without the FA synthesis? Or 15%??


Monday, 1 July 2013

High glucose induces adipogenic differentiation

This is probably old news to some or most people. I myself have known for along time, just from intuitive observation of my own body, that there is something quite "fattening" about spiking your blood sugar.

High glucose induces adipogenic differentiation of muscle-derived stem cells

An In Vitro Model to Probe the Regulation of Adipocyte Differentiation under Hyperglycemia.

Again, just the title of these studies tells you what you need to know. In the first study, high glucose concentrations induced adipocyte differentiation of stem cells from adipose tissue. ( the glucose concentration used was very high, 25mM, so take it as you will. Also was done in vitro. )

Further down in the study results we also see how high glucose even makes muscle stem cells turn into adipocytes!

The mechanism by which this seems to be happening is ROS production signalling.....

The simplest interpretation of the data are that ROS produced in response to high glucose, by stimulating PKCβ (and possibly other effectors), act as a differentiation signal for adipogenic conversion of muscle derived stem cells.


In conclusion, we demonstrate that high glucose has an adipogenic potential on stem cells derived from both the adipose tissue and skeletal muscle, and we provide some insight into the signals and molecules that underlie this process. 

I think this is part of the puzzle as to why refined carbs in particular can be so fattening. It is well documented that the digestibility of carbohydrates determines the corresponding postprandial blood sugar spike ( glycemic index ). In addition, I suppose you could say that, being insulin resistant in muscle leads to exaggerated and prolonged elevated postprandial glucose levels, and these high glucose concentrations ( could potentially ) activate adipogenic pathways, in both muscle and fat tissue.

Granted, not everyone gets massively fat from spiking their blood sugar. We know that already. Another frustrating fact we all know, is that, stopping the blood sugar spikes and removing carbs from your diet doesnt magically return you to a state of complete health and lean-ness. Its as if the damage done by the historical blood sugar spikes is permanent.  ( like maybe, getting new fat cells ) .