The same gene can have different effects in different species

(Neuromedin U in the brain has anti-obesity properties in mice but not rats)

November 18, 2022

Author: Manish Verma

Editor: Dr. Jitendra Kumar Sinha

Have you ever pondered why people with varying dietary habits tend to have distinct body shapes? A person who overeats, for instance, may have a slim physique, but a diet-conscious individual may yet suffer from obesity. The disparities in our eating patterns and metabolism rates are contributing factors, but our neural genetic systems and the way they regulate our appetites are also to blame.

Hormonal and neural impulses govern our sensory desires, which could range from rage to hunger. These urges often manifest as behavioral patterns, triggered by intricate biochemical processes. Some of the genes that code for the proteins involved in these processes are expressed in the body to create the corresponding components.

For example, the neuronal protein hormone known as Neuromedin U (NmU) has been linked to a wide range of physiological functions across a number of animal species, including mammals. It plays a role in the metabolism of energy use, eating habits, the maintenance of the circadian rhythm, tumour growth, and immune response. Its “anti-hunger” (anorexigenic) function has been documented in animal models, including mice. This makes it a potential target for anti-obesity drugs that work by stopping the body from wanting to eat more than it needs. Pharmaceutical investigations have revealed that NmU reduces food intake and increases energy expenditure in mice. Mice that lack NmU are more likely to overeat, have a low body temperature, become lethargic, and put on weight. Even though the main role of NmU in energy metabolism is still up for debate, different results have been found in trials with rats that used the same treatment.

Researchers have found that NmU mRNA expression in the rat pituitary pars tuberalis (PT) is significantly higher during the light phase and lower during the dark phase. This occurs because melatonin curtails the expression of NmU mRNA during the dark phase. Now, the same researchers have looked at whether NmU in PT is linked to the nocturnal eating habits of rats caused by their circadian cycles.

Figure 1: Reproduced directly from Yokogi et al., 2022

Figure 2: In rats, endogenous NmU did not enhance food intake or produce obesity, demonstrating that it is not an anorexigenic hormone. (Credits: Sayaka Aizawa from Okayama University)

They intended to look at the anorexigenic activity of NmU in rat models with and without this neuropeptide. To that purpose, they used the rGONAD (rat genome-editing by oviductal nucleic acid delivery) approach to produce rats with the NmU gene silenced. These rats, known as NmU KO (knockout) rats, were unable to synthesize the neuropeptide. To the team’s astonishment, unlike NmU KO mice, NmU KO rats did not increase their food intake and didn’t become fat.

The hormone NMU has been researched for its role as a feeding suppressor, but it is now obvious that it has a multitude of other roles, even among closely related species. But more research needs to be done to find out if rats or mice are a good model for the physiological and behavioral responses of NMU in humans.

Abbreviations:

NmU – Neuromedin U; KO – Knockout; PT – pars tuberalis

References:

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