An enzyme that leads to weight loss without affecting appetite or food intake
Researchers have discovered how a cluster of specialized cells in the brain can cause obesity.Scientists have discovered the mechanism by which a cluster of astrocytes (specialized brain cells), in the hypothalamus causes obesity in mice. As part of the new study, biologists have also identified an enzyme that inhibits this process, resulting in weight loss without affecting appetite or food intake.
The hypothalamus of the brain contains key areas that control food intake and energy expenditure. They house most of the neurons involved in nutrition and body weight control. Gamma-aminobutyric acid (GABA) is the dominant neurotransmitter in the hypothalamus, acting on GABA A. The inhibitory neurotransmitter GABA helps provide energy for the body to function by controlling hunger and signaling satiety. When a person is full, GABA blocks the hunger signal so that there is no overeating.
The lateral hypothalamus (LH) is known as the "hunger center" of the brain. When it is stimulated, it triggers the sensation of hunger. Although it is known that LH neurons are associated with adipose tissue and are involved in fat metabolism, its mechanism of action to regulate fat metabolism remains unclear.
A new study from the Institute of Basic Sciences in South Korea examined cells in the lateral hypothalamus of mice, focusing on the role that astrocytes play in the regulation of fat metabolism.
A group of neurons in the hypothalamus specifically express the alpha-5 subunit of the GABA A receptor, GABRA5. The researchers found that mice with diet-induced obesity exhibited a slowing of GABRA5 neuronal stimulatory activity.
Chemogenetic inhibition of GABRA5 in mice resulted in decreased heat production (thermogenesis) in brown adipose tissue (BAT), leading to fat accumulation and weight gain. However, when hypothalamic GABRA5 neurons were reactivated, the mice lost weight. Therefore, the researchers hypothesized that GABRA5 neurons act as a weight regulation switch.
Studying this process more closely, the researchers found that reactive astrocytes in the LH regulate the activity of GABRA5 neurons. Unlike typical astrocytes that perform metabolic and neuroprotective tasks in the central nervous system, astrocytes that become reactive in response to pathological conditions inhibit these auxiliary functions.
Reactive astrocytes from obese mice overexpressed monoamine oxidase-B (MAO-B), the enzyme responsible for the synthesis of GABA by astrocytes. Although scientists noticed that MAO-B overexpression inhibited surrounding GABRA5 neurons, when the researchers suppressed the MAO-B gene in the reactive astrocytes, it decreased GABA secretion, reversing the inhibition. This increased thermogenesis in the fatty tissues of obese mice, leading to weight loss even when they followed a high-calorie diet. The findings, the researchers said, suggest that the MAO-B enzyme produced by reactive astrocytes could be an effective target for treating obesity without affecting appetite.
The study was published in the journal Nature Metabolism, and the video below, created by the Basic Science Institute, clearly shows the results of the study.