Mechanism of Fatty Acids Anti Inflammatory Effects – Explained?

Most Nutritional Therapists are comfortable in the concept and application of concentrated essential fatty acids especially fish oils as a means of altering abnormal inflammatory pathways in the body. Some EFA’s are perceived to be anti-inflammatory and others pro-inflammatory. Whilst the simplistic dichotomy of interpretation (Omega 3 Anti/Omega 6 Pro) has kept many a student content that they have mastered the art of complex fatty acid biochemistry – the reality is that cell membranes operate in a state of competitive inhibition with fatty acids of all carbon chain lengths and their role is highly sophisticated and complementary.

So…the paper out in the journal Cell this month (Sept 2010) from the lab of Prof. Olefsky at the University of California is a really exciting addition to the extensive research available – in that it elegantly describes a key anti-inflammatory mechanism using a G-protein coupled receptor.[1]

G proteins (guanine nucleotide-binding proteins) are a family of proteins  involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors.

This particular protein (GPR120) is an essential component for the activation of the anti-inflammatory mechanisms inside macrophages – a key family of white blood cells that devour invaders – to assist with inflammation control. These are an important part of obesity and diabetes management as inflammation reduces insulin sensitivity and predisposes people to insulin resistance and later on type 2 diabetes.

The researcher’s state:

In conclusion, GPR120 is a functional ω-3 FA receptor/sensor and mediates potent insulin sensitising and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.

This group found that Omega3 FAs (docosahexaenoic acid (C22:6n3, DHA) and eicosapentaenoic acid (C20:5n3, EPA)), the major ingredients in fish oil, exert potent anti-inflammatory effects through GPR120

Fatty Acids inhibit Inflammation through the GPR120 receptor disengaging two inflammatory triggers called: TAB1 and TAK1

So why do we care? Well chronic activation of inflammatory pathways plays an important role in the pathogenesis of insulin resistance and the macrophage/adipocyte nexus provides a key mechanism underlying the common disease states of decreased insulin sensitivity.[2]

Syndrome X is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.  It affects one in five people, and prevalence increases with age. Some studies estimate the prevalence in the USA to be up to 25% of the population and this may well be reflected in the UK where we have a very similar dietary pattern.[3]

The migration of monocytes/macrophages to adipose tissue (including intramuscular fat depots) and liver provide subsequent activation of macrophage proinflammatory pathways and cytokine secretion. Then through paracrine effects, these events promote inflammation and decreased insulin sensitivity in nearby insulin target cells.[4] Meaning that the use of suitable doses of fish oils, especially with a high DHA content will provide a strategic way to alter risk of diabetes and aid in blood sugar control.

Key comments

Whilst this is a mouse model the implications for the mechanisms that EFA’s employ for the management of inflammation are profound. This group demonstrate that DHA has a direct immunological impact that translates into potential viable clinical outcomes.

Thus, they state:

DHA stimulation of GPR120 inhibits both the TLR2/3/4 and TNF-α proinflammatory cascade. Recent studies have also indicated that metabolic products derived from ω-3 FAs, such as 17S-hydroxy-DHA, resolvins, and protectins may play a role in the long term resolution of inflammation and this might attenuate insulin resistance in the context of obesity.[5]

This means that EFA’s have more than one route to effect – this is great news as many drugs target a single enzyme, natural agents often beneficially influence several mechanisms at the same time providing less side effects and a positive outcome.

Highlights

If you find this interesting why not listen to Prof. Jerrold Olefsky as he takes you on a brief, personally guided tour of his lab’s discovery of how omega-3 fatty acids in fish oil squelch inflammation and protect obese mice from diabetes.

Finally, the role of fatty acids are unlikely to be based around this one receptor –GPR120. Previous studies demonstrate that fish oils have diverse benefits on multiple tissues. For example, Omega-3 fatty acids can inhibit the production of proinflammatory eicosanoids and serve as precursors for resolvins, (i.e., protective lipids that help reduce inflammation). In addition, fish oils help prevent cardiovascular disease and have positive effects on many inflammatory disorders, such as arthritis, asthma, and ulcerative colitis. The cod liver oil so many of us avoided at school may yet turn out to be one of nature’s most marvellous products.

References

[1] Oh da Y, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, & Olefsky JM (2010). GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 142 (5), 687-98 PMID: 20813258

[2] Schenk, S., Saberi, M., & Olefsky, J. (2008). Insulin sensitivity: modulation by nutrients and inflammation Journal of Clinical Investigation, 118 (9), 2992-3002 DOI: 10.1172/JCI34260

[3] Ford, E. (2002). Prevalence of the Metabolic Syndrome Among US Adults: Findings From the Third National Health and Nutrition Examination Survey JAMA: The Journal of the American Medical Association, 287 (3), 356-359 DOI: 10.1001/jama.287.3.356

[4] Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007 May;132(6):2169-80. Review. View Abstract

[5] González-Périz A, Horrillo R, Ferré N, Gronert K, Dong B, Morán-Salvador E, Titos E, Martínez-Clemente M, López-Parra M, Arroyo V, Clària J.Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 2009 Jun;23(6):1946-57. Epub 2009 Feb 11. View Full Paper

Related articles:

  1. Omega-3 Fatty Acids – A Promising Novel Therapy For Non-Alcoholic Fatty Liver Disease
  2. Omega-6 Fatty Acids and Risk for Cardiovascular Disease
  3. Fatty Diet Suppresses Immune System
  4. Transcriptional Regulation of Inflammatory Pain and Hyperalgesia: NF-kB as a Lynchpin and Master Regulator.
  5. Antioxidants prevent health-promoting effects of physical exercise in humans

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