Research Blog

Newly Discovered Molecule BAIBA Important Signal for Exercise Benefits


A new molecule released by skeletal muscle during exercise is found to increase brown fat composition in the body. The molecule, BAIBA, is shown to be inversely correlated with cardiometabolic risk factors in humans.

A team of researchers has found a new molecule, or myokine, that may be responsible for many of the beneficial effects of exercise.  The myokine is BAIBA (ß-aminoisobutyric acid). Myokines are a growing class of cytokines that are released by the skeletal muscle myocytes into the blood stream to cause effects on other tissues throughout the body. The study (ß-aminoisobutyric acid Induces Browning of White Fat and Hepatic Beta-Oxidation and Is inversely Correlated with Cardiometabolic Risk factors, 2014. Lee Roberts, et al.) was published in Cell Metabolism and was featured in Science and Nature.  

We enthusiastically reported in 2013 that exercise generates browning of white fat, a process mediated by PGC-1alpha. Brown fat is important because it essentially transforms calories into heat by decoupling ATP production and glucose breakdown. In addition, brown fat reduces white adipose tissue stores and raises glucose tolerance. At the time, however, it was unknown how PGC-1alpha, which is produced and remains in the skeletal muscle in response to aerobic exercise, could generate effects on remote adipose tissue without leaving the skeletal muscle myocyte. In the past decade or so it has become increasingly clear that the skeletal muscle serves as a pseudo-endocrine gland by releasing myokines. For example, irisin is a hormone released by skeletal muscle recently discovered to cause the browning of white adipose tissue. Irisin was discovered in 2012. It appears that BAIBA plays a similar role to irisin. While irisin is a protein hormone, BAIBA is much smaller, consisting of just a single amino acid. BAIBA is derived from the amino acid valine, but does not itself play a role in building proteins (the primary role of amino acids).  

In summary, aerobic exercise produces PGC-1alpha generating BAIBA release into the bodys circulation. BAIBA then acts on white adipose tissue to transform it into brown fat via PPARalpha. Brown fat generates heat from fat, essentially burning calories and raising the bodys metabolism. BAIBA also stimulates hepatocytes (liver cells) to begin breaking down fatty acids via beta oxidation. A graphic summary is pictured in the figure below.

the physiological role of BAIBA in response to exercise

BAIBA was discovered by focusing on PGC-1alpha. PGC-1alpha is a transcriptional coactivator, which means it regulates gene expression. PGC-1alpha expression in response to aerobic exercise has been shown to cause a myriad of metabolic changes that increase endurance and raise the metabolic rate. When PGC-1alpha was over expressed in myocytes, four metabolites were found to be increased: BAIBA, GABA, cytosine and 2’-deoxycytidine. Out of these four molecules, only BAIBA was found to increase the expression of brown adipocyte-specific genes. In human pluripotent stem cells undergoing differentiation to white adipocytes, BAIBA increased the brown fat thermogenic phenotype. When mice were treated with BAIBA in their drinking water, brown fat composition increased relative to non-treated controls.  It appears that BAIBA exerts its effect on hepatocytes and white adipocytes through PPARalpha, a nuclear receptor protein. The study also investigated how PGC-1alpha increases BAIBA expression. It appears to act through expression of a number of enzymes responsible for BAIBA production.

In addition to increasing brown fat, treating mice with BAIBA increased their metabolism and glucose tolerance while decreasing their body weight.  Metabolism was measured with oxygen consumption (VO2). BAIBA mice had higher oxygen consumption, suggesting increased calories were burned. After 15 days of drinking water infused with BAIBA, the mice were found to have significantly reduced body weight. Despite the increase in metabolism, the BAIBA treated mice did not consume significantly more grams of food from the control mice. The graph below demonstrates the ability of BAIBA treatment to reduce body fat composition in mice.

BAIBA Reduces Body Fat in Mice

Perhaps most intriguing, was the influence of BAIBA on human health indicators. The study utilized data and samples from the Framingham Heart Study, which was a longitudinal, community based analysis of 2,067 people. Plasma BAIBA levels were inversely correlated with the following negative health indicators: fasting glucose, insulin resistance, triglycerides and total cholesterol. Furthermore, results from the HERITAGE Family Study, a 20 week exercise intervention for previously sedentary Americans, showed that plasma BAIBA concentration increased by 17%. Thus, the results found in mice appear to translate over to humans with respect to BAIBA.

BAIBA may prove to play a pivotal role in fighting obesity and related diseases such as diabetes. The authors suggest that one day BAIBA could be incorporated into drugs for fighting obesity if it proves to have no unforeseen side effects in animal studies. It will certainly be interesting to see the medical impact of BAIBA in a few years. For now, however, keep exercising because there is no pharmaceutical substitute.

Ghrelin: The hormone that suppresses your appetite after an intense workout

strawberries appetite exercise ghrelin

The hormone ghrelin is the only known hormone to directly cause appetite. Acute bouts of exercise suppress it, but long-term exercise programs have no effect on ghrelin levels.

Ghrelin is sometimes called the “hunger hormone” because the peptide hormone is a powerful appetite stimulant. Ghrelin is 28 amino acids in length and assembled primarily in the stomach fundus. The hormone was discovered in 1999 and the subsequent decade saw a flurry of research on the influence of exercise and food intake on ghrelin. A comprehensive review published in the September 2013 issue of Appetite provides a nice summary of this research (Exercise and Ghrelin.  A narrative overview of research, 2013. King, et al.).

Ghrelin exists as an acylated and unacylated hormone. The acylated form binds to a Growth Hormone activating receptor, which generates appetite and subsequent feeding. The unacylated form produces a variety of metabolic effects, but its relationship to exercise is not as well understood and, thus, will not be discussed further here. Ghrelin administration promotes weight gain by reducing fat oxidation (the break down of stored fat), limiting energy expenditure and increasing fat storage. Interestingly, ghrelin administration causes individuals to seek energy dense, high-fat foods. In agreement with its role in maintaining weight balance, ghrelin levels in the body vary inversely with BMI. Therefore, obese individuals have low levels of ghrelin and vice versa.

Appetite is suppressed after an intense workout or race. This seems counterintuitive: appetite is suppressed at the time the body is most starved of energy.  Regardless of the reason, ghrelin provides the signal for appetite suppression following intense exercise. Ghrelin levels are reduced in the 30 minutes following intense exercise. One study found that treadmill running at 75% of VO2 max significantly suppressed ghrelin, but treadmill running at 50% of VO2 max had no effect on ghrelin levels. Thus, acute exercise suppresses ghrelin post-bout at an exercise intensity threshold. Whether this is a graded suppression response above the threshold has not been studied.  

Although an acute bout of exercise produces a transient response, it appears to produce no long-term effect on ghrelin levels. Ghrelin levels in study participants the morning following an intense exercise bout showed no difference from non-exercised controls. This is surprising because it suggests that the body does not recover the energy expended during the intense exercise bout. In fact, a study done on a cyclist in the Tour de France found that energy consumption did not compensate for energy expended on tough climb days. In other words, the cyclist had a negative energy balance. In contrast, ghrelin levels are responsive to energy deficits induced by food restriction. One study found that creating a negative energy balance by restricting calories in meals generated a strong increase in ghrelin levels 9 hours into the calorie restriction. However, creating an identical negative energy balance with a 90 minute run produced no perturbation of ghrelin levels 7.5 hours later. Thus, it appears that a food intake disturbance to energy balance, but not an acute exercise disturbance, continues to influence ghrelin levels more than 2 hours post-disturbance. The figure below illustrates the results of the discussed study.

Effect of Exercise and Food Restriction on Ghrelin Over a 9 Hour Trial

What about long-term exercise programs? Long-term exercise programs do not influence ghrelin levels directly. Instead, exercise acts through changes in body mass to modify ghrelin levels. Total ghrelin levels measured during a fast increase with the amount of weight lost during the exercise program. This may be one reason why participants in weight loss programs find the initial pounds the easiest to shed. However, one study found that females did increase acylated ghrelin levels in response to an exercise intervention program, regardless of whether or not a steady energy balance was maintained with increased food intake. Yet, no changes were observed in males.

Obese individuals generally have reduced ghrelin sensitivity. That is, ghrelin levels are  abnormally low during a fast and  then remain low following a meal, showing little fluctuation. However, researchers have found that a long-term exercise intervention reduced ghrelin suppression during a fast and lowered ghrelin following a meal in obese subjects. Thus, exercise produces greater ghrelin fluctuation in obese individuals, which causes increased appetite and hunger during a fast and higher satiety following a meal.

It is important to remember that appetite and the amount of food we eat is influenced by many factors. Recall from a previous post on exercise’s influence on brain activity that the hormone leptin plays a critical role as well. Research on exercise’s effect on appetite is still in its infancy; the studies presented here provide many more questions to be answered.

Copyright © 2022  All rights reserved.