C15:0’s Essentiality May Go Back 20 Million Years

Healthy Aging

Groundbreaking Discovery Around A Short List of Essential Long-Chain Fatty Acids (Including C15:0)

Last week, PLOS Biology released an exciting peer-reviewed paper with a clunky title but simple discovery: Namely, that single free fatty acids, absent of all other nutrients, enabled healthy development and growth – at least in baby worms. Importantly, there was a short list of five most-important (aka, most essential) fatty acids, each of which, on their own, enabled development and growth.

One of those fatty acids? C15:0, of course. So, let’s dive in to understand why this study is such a big deal.

What was the purpose of this baby worm study?

In their study, Ruan et al. wanted to evaluate the following:

• Are there single fatty acid nutrients that, in the absence of all other nutrients (including carbohydrates and amino acids), support healthy growth and development?
• If so, do these individual nutrients simply supply energy support for genetically-driven development, or are they true gate-keepers that directly turn on switches that cause growth and development?
• If these individual nutrients directly drive development, how are they doing it?

More simply said, this team was hunting for which, if any, individual nutrients are truly essential to driving baby development and growth.

So, why worms?

Ruan et al. used worms (or the more sciency-term, nematodes) called Caenorhabiditis elegans. C. elegans are often used for initial studies evaluating molecules that affect development and longevity. For this particular study, C. elegans was ideal for the following reasons:

• As shared by Memar et al., the early development of these worms has been well conserved, even between species, for over 20 million years.
• In their early postembryonic state, these worms will “pause” if starved, awaiting the right milieu to restart their development. In contrast, mammals simply die.
• Additionally, C. elegans have important health-related pathways that are shared with humans, including AMPK, mTOR, and PPARs.

Got it. How did this study identify the essentialist nutrients for baby development?

One by one, Ruan et al. evaluated which of the following nutrients could effectively change young and “paused” worms back to growing and developing worms:

• Free saturated fatty acids (C2:0, C3:0, C4:0, C8:0, C15:0, C16:0, C17:0)
• Saturated fatty acid metabolites (acetyl-CoA, β-hydroxybutyrate)
• Free unsaturated fatty acids (oleic acid, linoleic acid, alpha-linolenic acid, arachidonic acid, and EPA)
• Glucose and carbohydrates
• Amino acid mix

I’m in. Which nutrients were truly essential to development and growth?

Amazingly, when starved baby worms were fed any of the five following nutrients in isolation (aka provided no other nutrients), the baby worms successfully developed and grew as if they were fed a full-nutrient diet:

• C15:0
• C16:0
• Oleic acid
• Linoleic acid
• Alpha-linolenic acid

Whittling this list down further to those fatty acids that human bodies do not readily make on their own, that leaves us with the three previously identified overall essential fatty acids for humans:

• C15:0 (an odd-chain saturated fatty acid)
• Linoleic acid (an omega-6 fatty acid)
• Alpha-linolenic acid (an omega-3 fatty acid)

How about that?

Okay, how do these essential fatty acids directly drive development and growth?

The PLOS Biology paper includes an impressive series of studies that allowed the researchers to identify three key mechanisms that these fatty acids use to directly drive healthy development and growth:

1. Inhibition of mTOR and activation of autophagy. By directly inhibiting mTOR, these free fatty acids enabled autophagy, which allowed for effective recycling of cells and nutrients to help the baby worms grow.
2. Activation of PPARɑ. Upon directly activating PPARɑ receptors, a previously unknown hormone was released in the gut. This hormone then literally went straight to baby worms’ central neurons in their head, which regulated insulin-like neuropeptides and orchestrated global development throughout their bodies. The result? Growing and developing babies.
3. Orchestrate whole-body growth. Science is best believed when it is consistent, right? Well, the roles of C15:0 as not only an essential fatty acid, but as an effective mTOR inhibitor and PPARɑ activator, have been demonstrated in other studies (including our own).

This all seems great for baby worms, but what does this mean to us humans?

While it’s safe to say that humans are slightly more complex than worms, the authors did conclude that C15:0 and a handful of other fatty acids function as “dominant signal nutrients” to get post embryonic development underway.

Why are these five fatty acids so unique? Well, as shared by Ruan et al., these dietary free fatty acids are:

1. Good indicators that proper foods are available to help a baby grow.
2. Readily absorbed by the gut.
3. Sources of high energy.

The take home message? When a baby eats these single free fatty acids, his or her brain is told, “You’re good to go, kiddo. Let’s get to developing your body and brain.”