HEALTH NEWS

Study Title:

Protein Drives Brain Activation of Metabolism and Alertness

Study Abstract

Hypothalamic orexin/hypocretin (orx/hcrt) neurons regulate energy balance, wakefulness, and reward; their loss produces narcolepsy and weight gain. Glucose can lower the activity of orx/hcrt cells, but whether other dietary macronutrients have similar effects is unclear. We show that orx/hcrt cells are stimulated by nutritionally relevant mixtures of amino acids (AAs), both in brain slice patch-clamp experiments, and in c-Fos expression assays following central or peripheral administration of AAs to mice in vivo. Physiological mixtures of AAs electrically excited orx/hcrt cells through a dual mechanism involving inhibition of KATP channels and activation of system-A amino acid transporters. Nonessential AAs were more potent in activating orx/hcrt cells than essential AAs. Moreover, the presence of physiological concentrations of AAs suppressed the glucose responses of orx/hcrt cells. These results suggest a new mechanism of hypothalamic integration of macronutrient signals and imply that orx/hcrt cells sense macronutrient balance, rather than net energy value, in extracellular fluid.

From press release:

Protein -- not sugar -- stimulates cells keeping us thin and awake, a new study suggests.


A new study has found that protein and not sugar activates the cells responsible for keeping us awake and burning calories. The research, published in the Nov. 17 issue of the scientific journal Neuron, has implications for understanding obesity and sleep disorders.


Wakefulness and energy expenditure rely on "orexin cells," which secrete a stimulant called orexin/hypocretin in the brain. Reduced activity in these unique cells results in narcolepsy and has been linked to weight gain.


Scientists at the University of Cambridge compared actions of different nutrients on orexin cells. They found that amino acids -- nutrients found in proteins such as egg whites -- stimulate orexin neurons much more than other nutrients.


"Sleep patterns, health, and body weight are intertwined. Shift work, as well as poor diet, can lead to obesity," said lead researcher Dr Denis Burdakov of the Department of Pharmacology and Institute of Metabolic Science. "Electrical impulses emitted by orexin cells stimulate wakefulness and tell the body to burn calories. We wondered whether dietary nutrients alter those impulses."


To explore this, the scientists highlighted the orexin cells (which are scarce and difficult to find) with genetically targeted fluorescence in mouse brains. They then introduced different nutrients, such as amino acid mixtures similar to egg whites, while tracking orexin cell impulses.


They discovered that amino acids stimulate orexin cells. Previous work by the group found that glucose blocks orexin cells (which was cited as a reason for after-meal sleepiness), and so the researchers also looked at interactions between sugar and protein. They found that amino acids stop glucose from blocking orexin cells (in other words, protein negated the effects of sugar on the cells).


These findings may shed light on previously unexplained observations showing that protein meals can make people feel less calm and more alert than carbohydrate meals.


"What is exciting is to have a rational way to 'tune' select brain cells to be more or less active by deciding what food to eat," Dr Burdakov said. "Not all brain cells are simply turned on by all nutrients, dietary composition is critical.


"To combat obesity and insomnia in today's society, we need more information on how diet affects sleep and appetite cells. For now, research suggests that if you have a choice between jam on toast, or egg whites on toast, go for the latter! Even though the two may contain the same number of calories, having a bit of protein will tell the body to burn more calories out of those consumed."

Study Information

Mahesh M. Karnani, John Apergis-Schoute, Antoine Adamantidis, Lise T. Jensen, Luis de Lecea, Lars Fugger, Denis Burdakov
Activation of Central Orexin/Hypocretin Neurons by Dietary Amino Acids
Neuron
2011 November
University of Cambridge