Newsletter #215

Hey guys! So, you might have heard about a new study that came out this week identifying a metabolite, inducible by exercise, that reduces appetite and energy intake. In mice, a high dose of this molecule suppressed their food intake by around 50%, and resulted in weight loss when administered over ten days. One would hope that this might eventually lead to some effective therapeutic interventions for obesity, which are sorely needed. But in the meantime, what exactly is this molecule, and how is it naturally activated? Like, can we take advantage of this pathway right now?

Maybe so. The metabolite in question is a modified amino acid known as N-lactoyl-phenylalanine (or Lac-Phe), synthesized from the essential amino acid phenylalanine and from lactate. Lactate is a byproduct of intense physical activity and is responsible for the “burn” you feel in your muscles when you’re working really hard. The concentration of blood lactate is usually 1-2 mmol/L at rest, but can rise to greater than 20 mmol/L during intense exertion. So if you want to increase levels of this metabolite, high-intensity exercise is probably gonna be your best bet.

But hang on a second, why would lactate reduce energy intake? Shouldn’t it have the opposite effect, since lactate is indicative of activity that is likely to incur higher energy expenditure? Well, it’s probably a mechanism to maintain circulation to active muscles. You see, when you eat, blood flow must be directed to your digestive system to break down food and absorb nutrients. So, it makes sense that lactate would induce appetite suppression, in order to block these competing blood flow demands, and that the impact of this signal might reverberate beyond the exercise bout.

(Of course, most athletes have probably already learned the hard way that eating and sprinting are kind of mutually exclusive activities)

In light of this new study, I decided to dig into the literature on the relationship between lactate and appetite. Hopefully this might inspire some of y’all to embark on some intense intervals today (just play it safe and be sure to stay hydrated - we are in a heat wave after all here in the US!).

Plenty of studies have shown that injecting lactate into rodents results in substantial appetite suppression and subsequent weight loss. But what about humans? Researchers in Switzerland recruited 12 healthy young men and had them visit the lab on two occasions. On one visit, they gave them an infusion of lactate, and on another they infused the men with saline (control). Shortly after each infusion, the men were subsequently treated to an all-you-can-eat buffet. The lactate infusion actually resulted in a fairly modest increase in blood lactate concentrations (to ∼3.5 mmol/L - remember that intense exercise can raise it to more than five times that), but it significantly decreased their food intake. Compared to when they were given the saline drip, the men ate 250 fewer calories at the buffet, or a 17% reduction.

Seventeen overweight men went to the lab for four different 30-minute long experimental conditions: continuous moderate-intensity exercise; high-intensity intermittent exercise; very-high-intensity intermittent exercise; and finally a resting (control) session. Participants were provided food 70 minutes after each session, and their energy intake was monitored for the experimental day and the day after. Energy intake was lower after the high- and very-high-intensity exercise at the meal they had 70 minutes afterwards and in the 38 hours post-exercise. This was accompanied by higher blood lactate levels (+6 mmol/L) and lower ghrelin (-30%) compared to the moderate intensity exercise.

Researchers had eight normal-weight active males complete four different experimental sessions: 1) moderate-intensity continuous training (65% V̇o2max); 2) vigorous-intensity continuous training (85% V̇o2max); 3) sprint interval training (repeated all-out sprints); and 4) control (no exercise). The sprint interval exercise elicited the largest change in blood blood lactate (+11 mmol/L), ghrelin (−37%), and appetite (−25%), and the reduced appetite and ghrelin levels lasted for longer, persisting up to 90 minutes postexercise. Energy intake post exercise was also lower after the sprint activity (-300 calories, or -15% less than the control). Across exercise intensities, exercise induced elevations in blood lactate were closely related to both appetite suppression and reductions in ghrelin.

Last October, they found that two females had given birth - but apparently on their own, without any genetic contribution from the males with whom they were paired. Perhaps a survival strategy for animals that are on the brink of extinction?

Funny side note: around 15-20 wild condors - meaning like 10% of the remaining wild population of these birds - apparently got together and decided to utterly trash one unlucky woman’s deck last summer.

Thanks for reading, enjoy the weekend, and we'll see y'all next week!

https://mailchi.mp/humanos.me/newsletter-215