It had been a while since I've been able to just sit down and write things out as I am now. These last 3 months have been hectic to say the least. With exams, the start of the new academic year, several research projects and my involvement in several organizations I haven't even been able to maintain even the slightest form of social life.
Just to give you a rough idea. But as it is with these things in the end, if you work long and hard enough it ends up paying off. And that has lead to some exciting prospects for the near future.
I have been asked to speak at 5 colleges in the month of November, and present a dissertation on new aspects in adipose physiology with respect to the treatment of obesity and obesity-related disorders. Apparently it was my unique take on several subjects and my recent research into the peroxisome proliferator activated receptor delta, that led to my being recommended.
| What Is This?
Peroxisome proliferator-activated receptor delta (PPARdelta) is the mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling.
To be able to speak before a critical academic crowd is of course an extremely exciting prospect for me. But it brings with it the strain of preparing a meticulously thought out and complete dissertation on the subject, adequate visual aids and enough preparation to avoid succumbing to the pressure. But then isn't this every scholar's dream?
I have begun writing the final paper, and I'm writing an English version alongside it, that I may hope to present as an article here on bodybuilding.com, or at least part of it, for our readers to enjoy.
For nearly a year now I have been working with 3 colleagues in an independent research group, tackling various problems. We've started a non-profit organization earlier this year, and what we can bring in as far as funds is spent on research equipment to hopefully put into practice some of our findings.
Along with the use of more expensive equipment at our respective colleges (three of us are still studying) with the hopes of ultimately coming to one or more papers we can submit for publication. Something that would definitely greatly advance our academic careers. They have also been gracious enough to join me in another adventure.
After minor, moderately successful previous projects with Higher Power Nutrition, we have once again joined forces and will be releasing several products in the near future. Most of it is very hush-hush until the date of release, because it concerns rather novel approaches. But its something we are all very excited about and looking forward too.
It's a new challenge to work in a landscape that is now devoid of ephedrine and prohormones as it forces us to really be innovative to come up with things that will work as good or hopefully better. Not to mention safer. It's also an open market now, and many companies are drowning because these recent developments have exposed their own lack of Research & Development.
In short these are extremely busy times, and I owe everyone an apology for not being as actively involved in the online community these last months. But as you can tell, there are many things to look forward to when I hit the scene again full-time. I'm looking forward to publishing some more articles in December, and this time around (I realize there have been one or two occasions where I wasn't so good with that) I will try my best to keep my word!
This is one of the topics I will be discussing in my dissertation next month. One of the more recent advances in the treatment of Type II Diabetes and obesity is the use of GLP-I or Glucagon-Like Peptide I as a target for treatment.
GLP-I is a 31 amino acid long peptide secreted in the intestinal tract, by the L-cells of the duodenum, and to a lesser extent by the islets of Langerhans and the central nervous system. Though GLP-I is a potentiator of insulin secretion, and may therefore seem rather unfit for treatment in the aforementioned disorders, it has other benefits that make it very attractive.
It has the potential to reduce appetite, increase insulin sensitivity, slow gastric emptying and digestion and promote glucose expenditure (Ahren et al, 1997; Meneilly et al, 2001). All of which would greatly ameliorate conditions of overweight or insulin insensitivity.
On top of that there is a way to circumvent the insulin secretion problem. While GLP-I is capable of increasing insulin biosynthesis and Beta-cell size on its own (thereby alleviating problems associated diabetes) (Tourrel et al, 2001; Wang et al, 2002), it is dependent on a blood glucose level of 4.3 mmol/l or higher to actually increase insulin secretion. Meaning that in combination with a low-carb diet GLP-I forms a unique and interesting target for the treatment of such disorders.
GLP-I reduces appetite, and with it food and water intake, by functioning as an anorexigenic hormone as well as an inhibitor of orexigenic hormones (Kiefer and Habener, 1999; Drucker, 2003; Turton et al, 1996). The signals promote satiety and create an aversion to further food intake. In both lean and obese subjects, administration of GLP-I lead to decreased food intake.
As an added benefit, GLP-I has neuroprotective benefits (Perry et al, 2003) and may play a role in learning. The method by which GLP-I actually signals the brain to do this is not yet clear.
It may be through direct production in the central nervous system, but more likely via either systemic GLP-I from the L-cells in the digestive tractus, or through peripheral signalling from afferent nerves located there that reach the paraventricular nucleus. A similar case with GLP's effects on slowing gastric emptying, which are likely the result of direct action in the digestive tract and nervous control.
A lot of GLP's effects on the other hand seem to be related to its effects on endocrine function. We already know that GLP produces somatostatin, and if glucose is high enough increases insulin and reduces glucagon secretion, but it also has effects on the release of ACTH (leading to increased cortisol) and LH (leading to increased testosterone).
Leaving us with an irreconcilable problem as to whether GLP-I is anabolic, anti-catabolic, or catabolic. Preliminary studies seem to point towards a more anabolic effect, but if this needs to be judged in light of GLP's effects on insulin, then we need to take care not to extrapolate this to situations of low glucose intake, when it no longer has an effect on insulin release.
Especially since acute stimulation (Kieffer and Habener, 1999) seems to preferentially increase ACTH, and with the extremely short half-life of GLP-I (just a few minutes) it's hard to see any increase as being chronic.
The latter seems to also be the main research-topic when looking at the practical application of this model to treat obesity : coming up with analogues that have a longer half-life. GLP-I is cleared by the reduction of the alanine at the N-terminal by the enzyme DPPIV, while its active part is located at the C-terminal. That leaves a lot of room for alternate amino acid sequences at the N-terminal to avoid destruction by DPPIV without compromising the activity of the peptide.
Of course such manufactured peptides will never make it to the supplement market, so the rest of us have to get by with the promotion of natural GLP-I. GLP-I release is triggered by the intake of glucose, fat or a combination of the two. Obviously taking in glucose is not an option since that would potentiate insulin increase and set us back to square one.
After all GLP-I is released every time we eat now and it hasn't helped us one iota. Eating fat is one option, this is the very reason why eating fat when dieting is not bad. But of course fat contains a high amount of calories. So substituting some of the lost carbs with fat is an acceptable means of aiding weight loss and increasing satiety for the healthy athlete, but if you have a few more pounds to drop, you may not have the luxury to fit in as many calories.
Well, it does appear that our good old trusty glutamine does seem to trigger GLP-I release and could be used as an alternative. Now keep in mind that glutamine, especially on a low carb diet, can be readily used as a fuel source and likely does not offer us that much more leeway than glucose. But it does stimulate GLP-I release both as a trigger and a potentiator and causes larger increases than glucose.
On top of that, supplementing glutamine on a low-calorie, low-carb diet is not such a bad thing anyway, considering it protects muscle by offering a readily available alternative to robbing muscle glutamine stores for energy. This once again confirms glutamine's duality in being utterly useless to a bulking bodybuilder, but absolutely essential during periods of serious calorie-restriction.
- Diamant M, Bunck MC, Rheine RJ, Analoga van Glucagon-Like peptide I (GLP-I) : een oud concept als nieuwe behandeling van patienten met diabetes mellitus type 2. Ned Tijdschr Geneeskd 2004; Sept 25 : 148 (39).
It's Role In Weight Reduction.
I touched on this subject briefly in my 5 part series on the physiology of fat loss, that interleukin-6 may be a very important target for the treatment of obesity and disorders like it.
Simply because IL-6 is a trigger located in the middle of a number of very important events in lipolysis and adipose regulation. Recent research seems to confirm this further. Suggesting that IL-6 is highly increased in obese people.
The reason for this seems to be a reaction against the increased adipose mass, since under certain conditions it appears IL-6 will increase leptin release (possibly part of the mechanism that elevates leptin in obesity), reduce expression of Lipoprotein Lipase and entirely independent of other hormonal factors, seems to slightly increase lipolysis in both omental and subcutaneous adipose tissue.
Although the same study does seem to question to in vivo relevance of the physiological increase of IL-6, it does mark IL-6 as an important subject for future research into fat loss.
- Trujillo ME, Sullivan S, Harten I, Schneider SH, Greenberg AS, Fried SK. Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro. J Clin Endocrinol Metab. 2004 Nov;89(11):5577-82.
Increase In Androgens In Obese Women
Likely Caused By Increase In Fat Mass
Several disorders like PCOS (Polycystic Ovarian Syndrome) are accompanied by obesity. Such women often have high levels of androgens, which was first attributed to a higher production and release from the classic sites of synthesis. But since such disorders are often accompanied by obesity, and that obese women often suffer increased levels of androgens as well, it leads to the postulation that the increased fat mass may play a key role, either indirectly or directly.
This is an ovary with PCOS. The dark spots are cysts on the ovary.
A recent study examined the production of androgens in adipose tissue and revealed a critical role for adipose tissue 17beta-hydroxysteroid dehydrogenase Type 5 in the conversion of androstenedione to testosterone. While the type 4 enzyme was also expressed to a higher extent, the type 5 was expressed more in subcutaneous adipose tissue and that correlated well with the increase in body mass index.
Activity of the type 5 enzyme was also higher after differentiation, again expressing the extreme importance of preventing adipose tissue differentiation in the treatment of obesity and related disorders, something that is still not getting enough attention in the current treatment regimens. Such studies once again show the many complications the increasing epidemic of obesity causes. Hormonal imbalances like this can cause a multitude of problems, including problems with reduced fertility.
- Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, Arlt W. Androgen generation in adipose tissue in women with simple obesity - a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. J Endocrinol. 2004 Nov;183(2):331-42.