Gamma-aminobutyric acid (or GABA) is a widely distributed four-carbon free amino acid that is replete in vegetables, fruits, and fermented foods. GABA is produced from L-glutamic acid by glutamate decarboxylase and functions as a major inhibitory neurotransmitter in the central nervous system [1]. The role of GABA in the central nervous system is associated with the regulation of synaptic transmission, improving sleeplessness and depression, augmenting immunity, and regulating insulin secretion [2].
Recent studies have highlighted GABA to be beneficial in several ways, with multiple biological activities of GABA attributed to insulin metabolism [3,4]. Notably, signaling through GABA receptors has been associated with body weight as well as the growth and maintenance of skeletal muscle [4].
GABA could therefore be a potential therapeutic for the prevention and treatment of obesity, and this article will provide an overview of the evidence in this regard. For a deeper dive into GABA itself, you can read our in-depth guide here.
GABA controls feeding and metabolism
GABA has been proposed to play a key role in the cognitive choice of the type, quantity, and quality of food by regulating the transmission of signals between neurons in the brain circuitry [5]. As the major inhibitory neurotransmitter in the mammalian brain, GABA has been implicated in controlling excitability, the processing of information, plasticity, and the synchronization of neuronal activity [6]. Additionally, the involvement of GABA in eating behavior has been supported in experiments using rodent models and GABA receptor agonists and antagonists. Changes in brain glucose concentration can modify the release of neurotransmitters. For instance, hypoglycemic periods inhibit GABA release in the substantia nigra and ventral tegmental area, which are areas that project to the frontal cortex (FC) and increase dopamine concentration and disinhibit the FC.
Rodent studies have shown that the consumption of a high-fat diet reduces GABA levels in the FC and hippocampus, which could likely hamper the inhibitory processes that underpin feeding behavior. These findings support the view that GABA is implicated in the brain mechanisms underlying obesity and overfeeding [6].
Again in rodents, cutting-edge genetic methods have shown that inactivation of GABA signaling in the areas of the brain responsible for appetite brings about severe weight loss and glucose intolerance in young animals, but only transient appetite suppression in older animals [7].
GABA's role in reducing insulin resistance
The islet cells of the pancreas possess GABA-A receptors in humans, and research has suggested that GABA has the potential to improve beta cell mass and function [4,8,9]. In addition, GABA can help mitigate insulin resistance, likely through increasing the gene expression of glucose transporter 4 [10]. GABA also prevents beta cells (that secrete insulin) from apoptosis and its deficiency impacts insulin signaling in the skeletal muscle and liver [4,11].
Oral treatment with GABA in rodents has shown beneficial effects on fasting blood glucose, improved glucose tolerance, and insulin sensitivity following feeding with a high-fat diet [12]. The mechanisms for this are likely due to the inhibition of obesity-related inflammation and upregulating regulatory T-cell responses. It also significantly reduced the gain of body weight in mice fed a high-fat diet [12].
GABA's anti-obesity effects
In rodents, GABA substantially inhibits body mass gain by suppressing adipogenesis and lipogenesis [13]. Histological analysis (staining using a microscope) of white adipose tissue also demonstrated that GABA decreased adipocyte (fat cell) size. At the same time, GABA administration decreased fasting blood glucose and improved serum lipid profiles and hepatic lipogenesis in obese mice fed a high-fat diet. Overall, these results suggest that GABA exerts an anti-obesity effect mainly via the regulation of lipid metabolism.
Summary
This article has explored some of the mechanistic underpinnings of GABA in eating behavior and its relationship with several organ systems and tissues implicated in weight control. Although much of the existing evidence exists in cell and rodent models, it nevertheless indicates that GABA could have potential applications as a therapeutic strategy for weight control and, as a consequence, help to address the challenging metabolic diseases associated with obesity.
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References
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