Is lower ability to burn fatty acids in muscle a contributor to adult obesity? A Lecture presented by Dr. Greg Henderson
Gregory C. Henderson, Ph.D.
Department of Exercise Science & Sport Studies
School of Art and Sciences
Dr. Henderson’s research is focused upon effects of exercise on macronutrient metabolism in humans. Differences between men and women, and effects of aging are of central interest. Dr. Henderson’s approach is to administer non-radioactive stable isotope-labeled metabolites (tracers) followed by mass spectrometry based analyses of blood and muscle samples.
Dr. Henderson assigned two articles to be read for his lecture on February 19, 2014:
Intramuscular lipid oxidation and obesity
Joseph A. Houmard
American Journal of Physiology – Regulatory, Integrative and Comparative PhysiologyPublished 1 April 2008Vol. 294no. R1111-R1116
Impaired plasma fatty acid oxidation in extremely obese women
John P. Thyfault , Raymond M. Kraus , Robert C. Hickner , Amy W. Howell , Robert R. Wolfe , G. Lynis Dohm
American Journal of Physiology – Endocrinology and Metabolism Published 1 December 2004 Vol. 287no. E1076-E1081
John Thyfault and his research team tested the hypothesis that muscle is less able to oxidize fatty acids in obese women. The study design was that fatty acid oxidation was measured in lean control women (BMI = 23), and this was compared to fatty acid oxidation in obese subjects (BMI = 41). Another group studied was comprised of obese women who had undergone postgastric bypass surgery and had lost weight (> 45 kg), and their weight was stable at least a year after the surgery (BMI = 34). All of the women were given fatty acid tracers in order to measure fatty acid oxidation in both resting and exercise conditions. The results were astounding. Obese women had about 25- 33% lower oxidation of fatty acids compared to controls, at rest and during exercise. Moreover, the women who had lost weight still presented with reduced rates of fatty oxidation compared to the controls. In fact, their fatty acid oxidation was very similar to the obese women who had not lost any weight.
This study demonstrates that obesity is associated with a lowering of the capacity to oxidize fatty acids, primarily in skeletal muscle. The main question raised by this article is, did the defect in fatty acid oxidation in obesity come first, and then the subjects became obese? Or did the defect in fatty acid oxidation occur only after the onset of obesity? This question is extremely difficult to answer, but Dr. Henderson felt that the lower fatty acid oxidation in obesity developed second, after obesity already was achieved.
What are the main take home points from this research?
1. No matter which came first, obese women have lower rates of fatty acid oxidation than their lean counterparts, and this would make it more difficult for obese patients to lose weight with exercise.
2. Therefore, it is especially important not to become obese in the first place, because once it occurs, the lowering of fatty acid oxidation in muscle makes it that much more difficult to lose weight. The diagram below illustrates this.
The above articles and some of Dr. Henderson’s own research will be discussed during the lecture.
Compared with that of MUFA, a high dietary intake of n-3 PUFA does not reduce the degree of pathology in mdx mice.
Henderson GC, Evans NP, Grange RW, Tuazon MA.
Br J Nutr. 2014 Feb 13:1-10.
Determinants of resting lipid oxidation in response to a prior bout of endurance exercise. Henderson GC, Alderman BL.
J Appl Physiol (1985). 2014 Jan;116(1):95-103. doi: 10.1152/japplphysiol.00956.2013. Epub 2013 Nov 14.
Kinetic measurement techniques in the evaluation of lipid metabolism. Henderson GC.
Curr Drug Discov Technol. 2013 Sep;10(3):209-23. Review
StearoylCoA desaturase-5: a novel regulator of neuronal cell proliferation and differentiation. Sinner DI, Kim GJ, Henderson GC, Igal RA.
PLoS One. 2012;7(6):e39787. doi: 10.1371/journal.pone.0039787. Epub 2012 Jun 22.
- Posted in: Biology of Obesity ♦ Exercise and Obesity
Being an Exercise Science major reading the article on “Impaired Plasma Fatty Acid Oxidation in Extremely Obese Women” to be very interesting. With obesity rates around the world rising it is important we know the physiological changes that occur in the obese population. According to this article the impairment of the oxidation of free fatty acids seems to be a cog in the component in this weight gain. Skeletal muscles from extremely obese individuals seem to exhibit a decreased lipid oxidation compared to those with lean muscle. They study was designed to compare free fatty acid oxidation during rest and exercise in female subjects who were lean, extremely obese, or post-gastric bypass patients who lost more than 45 kg. They were able to compare these women with the use of tracers and indirect calorimetry. The lean group had shown to oxidize more plasma free fatty acid measured by percent fatty acid uptake oxidized at rest as well as during exercise than the other two groups. This study also showed that extremely obese women and post-gastric bypass women who lost weight posses defects in plasma free fatty acid oxidation which may lead to excess weight gain and other co-morbidities including hypertension and cardiovascular diseases.
As I learned from this article skeletal muscle plays a key role in the utilization of lipids supplied to circulation. The skeletal muscle helps oxidize the fatty acids, but if they are unable to do so there is an increase in fat storage in the skeletal muscle and adipose tissue. It seems that the impairment has to deal with the composition of the skeletal muscle fibers. According to the study the percentage of type I skeletal muscle fibers has a positive correlation with the amount of total weight lost over time. This seems to make sense because in the case of trained athletes (those mainly with leaner muscles) they have greater capillary density and have an increase in fat mobilization and fat-metabolizing enzymes. That means those who are trained and have a greater number of muscle fibers increase beta oxidation as the muscles mitochondria have a great capacity. I wonder if it is possible to have a supplement to give to those who are overweight that can increase enzyme activity allowing them to oxidize higher levels of these fatty acids along with incorporating exercise regiments to increase the percentage of muscle fibers. All in all it seems that a key component in weight gain and obesity seems to be the inability of skeletal muscles to oxidize plasma fatty acids especially in those who have become obese.