Exercise to lose weight and reduce lipotoxicity!

Thanks to reader Cody for finding a study I had come across previously regarding IMCL/IMTG.  Actually the study linked to was an update, but there's a secondary lesson, I believe, to be had from the results.  Since this was a study in older folks, there's a sub-message here:  it's never too late!

Study:  Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete’s paradox revisited

We previously reported an “athlete’s paradox” in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content.

The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin- resistant, older subjects. Twenty-five older (66.4 0.8 yr) obese (BMI 30.3 0.7 kg/m2) men (n 9) and women (n 16) completed a 16-wk moderate but progressive exercise training program.  

Body weight and fat mass modestly but significantly (P 0.01) decreased. Insulin sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased (21%, P 0.02), with modest improvements (7%, P 0.04) in aerobic fitness (V˙ O2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary density, and fiber type were performed on skeletal muscle biopsies.  Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measured by mass spectroscopy, were decreased (n 13; 29% and 24%, respectively, P 0.05) with exercise training.   SDH (19%), glycogen content (15%), capillary density (7%), and the percentage of type I slow oxidative fibers (from 50.8 to 55.7%), all P 0.05, were increased after exercise.

In summary, these results extend the athlete’s paradox by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity.

Here's a link to the preliminary work I believe I was looking for (from the references in the above paper):
Skeletal Muscle Lipid Content and Insulin Resistance: Evidence for a Paradox in Endurance-Trained Athletes

So I've blogged a bit about lipid accumulation in non-adipose tissue, lipotoxicity and insulin resistance.  IMCL seems to correlate with IR, but the "athlete's paradox" is that insulin sensitivity accompanies increases in IMCL in athletes.  Therefore IMCL cannot be "toxic" in and of itself.  In this study we see that exercise decreases diacylglycerol and ceramide levels at the same time as IMCL's increase.  The negative effects of IMCL appear to be correlated to the build-up of metabolites rather than the stored triglycerides themselves and/or the turnover of  IMCL -- it's a secondary storage tank in the obese, but perhaps more like a gas tank for the athlete.  Perhaps ceramide is the sole culprit, insulin sensitivity, oxidative capacity and IMTG all increased by around 20%.  Ceramide and DAG both decreased, but only ceramide decreases correlated with insulin sensitivity improvements.

But ... in reading the originally referenced article, something else jumped out at me.  They took 25, mainly weight stable, obese, older (avg age ~66), sedentary people and, near as I can tell, did not change their diet.  One can presume most of these were eating a SAD before and after.  The participants were simply put on a moderate exercise regime.  The exercise was 45 min cardio (moderate by heart rate and/or perceived exertion), 4-5X/week -- mostly walking or stationary cycling.  You know ... the type of exercise often poo pooed in the low carb community that can only, according to Taubes, make you hungrier and cause you to eat more.  The subjects actually averaged 3.5X/week for the 16 weeks of the study.  

The result?:   In 4 months an average loss of almost 3-3/4 lbs of fat mass.  If continued for a year, this would translate into an average of 11 pounds in a year.  Not too shabby when compared to the weight losses reported by Shai et.al., but more importantly this counters to oft-repeated claim that you can't lose weight by exercise alone.  

And health-wise?  Insulin sensitivity improved >20%  (even as IMCL increased), as ceramide and diacylglycerol decreased.  IOW, whatever the cause of the IR, exercise alone improved this state.  

So exercise CAN improve health independent of diet.