Monday, September 12, 2011

Cardio, Fat and IGF-1: Study Investigates Modulatory Effect of Endurance Exercise and High Fat Meals on IGF1 Binding Protein Levels in Obese Human Subjects

Image 2: 3D structural model of the IGF1 protein (rendered by Emw)
It's probably less than 24h ago, that you read about growth hormone (GH) here, at the SuppVersity. Its increase during fasts was one of the points, I addressed in yesterday's installment of the Intermittent Thoughts on Intermittent Fasting series. In fact it has been known for quite some time now, that fasting does increase the release of the 191-amino acid, single-chain polypeptide from the anterior pituitary gland, which in turn facilitates the (mostly) desirable switch to non protein-catabolic metabolic state, where fat becomes the major energy substrate. GH's growth promoting magic, on the other hand is believed to be largely mediated by the growth hormone induced production and release of insulin like growth factor 1 (IGF-1) in the liver, as well as directly at the level of target tissues. Apart from the sheer amount of IGF that is produced, its binding to respective carrier proteins, so called insulin like growth factor binding proteins, or IGFBPs, is yet another major determinant of the half-life and more importantly the mode of interaction of the IGF peptides with their target receptors at the cell surfaces.

From previous studies into the effects of exercise on IGF-1 levels activity, we already know that trained endurance athletes exhibit higher levels of IGFBP-1 (insulin like growth factor binding protein 1) than their sedentary counterparts (Manetta. 2003). Other studies have shown that after acute (vs. chronic) bouts of aerobic exercise the levels of IGFBP-1 return to baseline within 12-24h (Nindl. 2009; Berg. 2008; Koistinen. 1996) In that, the IGF-binding effect of exercise appears to be restricted to endurance type of exercises, as a more recent study by Nindl et al.found no increase in IGFBP-1 levels in young lean women after 8 weeks of strength training (Nindl. 2010).
Image 2: Ronny Coleman's belly is recurrent topic on various bulletin boards. This image was part of a discussion on the muscular development forum. Is it s imply fat or the results of the false(?) belief in "the muscle building magic" of IGF-1? (photo by Dan Ray for MuscularDevelopment.com)
The results from the Nindl study are also important in view of the interpretation of "increased" or "reduced" endogenous (i.e. produced by the body) IGF-1 levels in terms of their purported anabolic effect on muscle tissue, as Nindl. et al. point out...
[...] increased lean mass, aerobic fitness, and upper and lower body strength resulting from an 8-wk exercise training programs can occur without concomitant increases in either circulating bioactive or immunoreactive IGF-I, as well as associated IGFBPs. In terms of reflecting positive anabolic neuromuscular outcomes, these data do not support a role for endocrine-derived IGF-I. (Nindl. 2010)
All horror stories about GH-guts aside, you may want to keep that in mind before you condemn all aerobic exercise as being anti-anabolic and pay a shitload of money for supplements that "have been shown in clinical trials" (why are you laughing? ;-) to increase IGF-1 levels.
From epidemiological studies (Heald. 2003; 2005), we also "know" (you are probably familiar with my antipathy against epidemiology) that high fat diets are associated with lower levels of IGFBP-1. It has also been implicated as more or less reliable predictor of cardiometabolic diseases in longitudinal studies (Heald. 2001). Reason enough for Prior et al. to probe the combined effect, or I should say, the interference of 6 months of potentially IGFBP-1 lowering aerobic exercise ("3 weekly sessions of 20 minutes at 50% of heart rate reserve and gradually increased to 3 weekly sessions of 40 minutes at 70% of heart rate reserve"), on the one hand, and IGFBP-1 suppressing high fat meals (84% was derived from fat, 13.7% from carbohydrates, and 2.7% from protein), on the other hand, in a group of 10 overweight (bodymass index = 28.7 ± 0.9 kg/m²), older (61± 2 years) men and women.
Figure 1: Effect of 6 month of aerobic exercise on serum free glucose, free insulin, HOMA-IR and IGFBP-1 levels in obese subjects (data calculated based on Prior. 2011).
As the data in figure 1 goes to show, the exercise regimen had profound beneficial effects on insulin sensitivity - evidenced by the increase in serum free insulin levels and HOMA-IR (considered a "reliable" long-term marker of insulin resistance). As previous research had suggested, these changes were accompanied by a major increase in IGFBP-1 (and thus presumably a decrease in IGF-1 receptor activity). The increase in IGFBP-1 was however (almost completely, cf. figure 2) 4h after the study participants consumed a single high fat meal.
Figure 2: Effect of high fat meal (84% fat, 13.7% carbohydrates, and 2.7% protein) on IGFBP-1 levels (data calculated based on Prior. 2011)
This negative effect of high fat feeding on IGFBP-1, as can be seen in figure 2, was almost identical before and after the 6-month exercise intervention, which led the scientists to conclude that despite the fact that ...
[...] aerobic exercise training has a potentially beneficial effect to increase fasting plasma IGFBP-1 concentrations in previously sedentary middle-aged to older adults  [..., a]erobic exercise training did not attenuate the adverse effect of a high-fat meal on plasma IGFBP-1 concentrations
Image 3: Germany's former foreign minister Joschka Fischer is a famous "victim" of the "low-fat-marathon-style-endurance-training" fat loss myth with built in YoYo-effect - I guess you will have your own celebrities with similar impressive "transformations" ;-)
and (you probably expected this) use this as a welcome opportunity for repeating the good (I should rather say "bad") old mantra of the benefits of chronic endurance exercise and low fat dieting.... I mean, come on. Look at our (Germany's) former foreign minister, Joschka Fischer (cf. image 3) - don't we all know that low-fat cereals and marathon running are no solution.

It would be nice to see some scientists going beyond this illusive paradigm, in order to gain insights into the underlying mechanisms or, even more fundamentally, to answer the question whether high(er) levels of free IGF-1 are causative or just corollary to cardiovascular disease, cancer and all the other maladies IGF-1 is currently held responsible for and which role all the healthy low-fat grains we are supposed to eat play in the etiology of these diseases... in case that is going to happen within my life-time, you can be dead-certain (pun intended) that the SuppVersity is the place, where you will read about it first.