Fat or Fire, What Comes First? Scientists Answer: Obesity Alone Triggers Inflammatory Signaling in Mice

The metabolic syndrome, i.e. the combination of obesity, inflammation and insulin resistance, is at the center of contemporary medical research. In my appearance on Carl Lenore's Super Human Radio, I already mentioned that from a logical perspective the mainstream belief, inflammation was the root of all evil, must be flawed. How should the reaction to a problem be the cause of the very problem itself? A recent study coming from a group of Korean scientists strengthens my conviction that out of the triad that not inflammation, but rather obesity or - one step further up in the genesis of the pathology - the combination of an unhealthy diet and a sedentary lifestyle is at the heart of the triad we now call the "metabolic syndrome".

Kim et al. investigated the pro-inflammatory signaling cascade in either diet-induced (DIO) or leptin gene deficient (ob/ob) obese mice and found that obesity alone ...

[...] up-regulated the expression of TLR1–9 and TLR11–13 in murine adipose tissues, a phenomenon linked with downstream nuclear factor κB [inflammatory protein linked to linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development], interferon regulatory factors, and STAT-1 activation, and up-regulated the expression of cytokines and chemokines via MyD88-dependent and MyD88-independent cascades [activate NF-κB].

Thus, obesity sets the scene for inflammation and inflammation in turn triggers a cascade of unfavorable metabolic and hormonal changes which in and out of themselves result in further weight gain...

Here, we have a self-enhancing pathologic circle, which - and this is probably an even more important result of the study - was especially "effective" in the group of diet-induced obese mice:

The magnitudes of the obesity-induced up-regulation of the TLR1, TLR4, TLR5, TLR8, TLR9 and TLR12 genes in the visceral adipose tissue were greater in the DIO mice than in the ob/ob mice. Similarly, the expression of the IFNα and IFNβ genes significantly increased in the adipose tissues of the DIO mice but did not change in the adipose tissues of the ob/ob mice.

So, its not in your genes, but in your hands, feet and mouth to ward off the plague of the 21st century: Exercise and eat healthy to get lean and/or stay lean and stave off inflammation and diabetes.

Omega 3 Attenuates Exercise Induced Rise in Inflammatory Markers, BUT is This Necessarily a Good Thing?

I want to take the results of a recent study (Bakhtyar. 2011) published in the Clinical Journal of Sport Medicine as an opportunity to readdress the question of whether or not the Omega 3 induced suppression of inflammation must be considered a good or a bad thing, both in view of athletic performance, as well from a health and longevity perspective.

Those of you, who listened to my interview on Carl Lenore's Super Human Radio show, will know that my understanding of "inflammation" is somewhat different from the mass market "explanation" of "a fire that causes damage". To be precise inflammation, or what scientists generally measure, is the release of signals (inflammatory markers) that tell immune cells to do their jobs. So, saying that inflammation is the root of all disease would be like saying that someone who calls the firefighters is to blame for the fire - but I am digressing from the topic at hand...

After administering 1.5g/day of an omega 3 supplement (experimental group) to every third of 45 previously untrained volunteers, Bakhtyar et al. found the subjects' "inflammatory" response to eccentric exercise to be modified:

The experimental group showed less elevation in TNF-α and PGE₂ immediately, 24, and 48 hours after exercise, when compared with the other groups. Significantly less elevation was shown in the concentration of IL-6, CK, and Mb for the experimental group at 24 and 48 hours after exercise. The experimental group also demonstrated a significant trend toward reduction in the plasma concentration of LDH immediately, 24, and 48 hours after the exercise program.

Now, what does this tell us about the training effect and health outcomes of the exercise regimen?

• With inflammation being a not yet fully understood prerequisite for muscular repair and hypertrophy, it would warrant further investigations like muscle biopsies and consistent training regimens with continuously monitored strength and muscle gains to conclude that omega 3 supplementation is beneficial in terms of physical performance.
• In view of the conclusions Pedersen draws in a recent review (Pedersen. 2011) of the role of exercise induced myokines, i.e. inflammatory markers released by muscles (myo- = muscle-), in chronic disease, blunting of muscular IL-6 release, which has been linked to muscular AMPK activation, increased glucose uptake and fat oxidation, omega 3 supplementation is probably counter-indicated in a health oriented exercise regimen, anyway.

I hope more scientists such as Pedersen will begin to question the current "anti-inflammatory" paradigm, so that major players in the medial landscape will be forced to take on their findings and stop portraying long chain polyunsaturated fatty acids in general and fish oil in particular as the savior of the fat and diabetic. Instead they should encourage people to finally get their asses off their sofas to induce exactly that amount of healthy, exercise-induced inflammation omega 3 supplementation appeared to suppress in the aforementioned study.

Omega-3 Fatty Acids PRO(!)-Inflammatory in Athletes

Although I am aware of the magnitude of studies providing evidence for the positive effects of omega-3 fatty acids in general and EPA and DHA, in particular. I think you should be aware that research on its effects in athletes (as the general effect of anti-oxidants on healthy people) are less unequivocal than those on positive effects on your average pre-diabetic fatso.

In a very recent study, scientists from the Unité de Formation en Sciences et Techniques des Activités Physiques et Sportives in France (Filaire. 2010) found that judo athletes who took a standardized omega-3 supplement (600 mg EPA and 400 mg DHA) for 6 weeks had significantly increased stress markers compared to placebo:

Significant interaction effects between supplementation and time on resting MDA [malondyaldehide] concentrations and Rmax were found (p = .03 and p = .04, respectively), with elevated values in the n-3 LCPUFA group after supplementation and no change in the placebo group's levels. The authors observed a significantly greater NO and oxidative-stress increase with exercise (MDA, Rmax, CDmax, and NO) in the n-3 LCPUFA group than with placebo.

I've also read reports from (recreational) athletes all over the Internet claiming that whenever their PUFA supplementation goes beyond 1-2g per day, they start feeling drowsy, lose energy, recover slower and show other signs typically associated with increased inflammation. Feel free to use the comment function to let us know how fish oil or other omega3 sources make you feel.