MSc Keshav Thapa’s doctoral dissertation revealed that the melanocortin 1 receptor, which is best known for its role in regulating skin and hair pigmentation, also has a critical role in in the liver’s ability to handle lipids such as cholesterol.
Metabolic disorders such as obesity, diabetes, and steatotic liver disease are on the rise globally, affecting millions of lives and posing one of today’s greatest public health challenges.
Dissertation research conducted at the University of Turku showed that the melanocortin 1 receptor (MC1R) plays as an unexpected yet critical role in the liver’s ability to handle lipids such as cholesterol and triglycerides.
“The newly discovered role of MC1R in liver metabolism could open new therapeutic possibilities on how we address metabolic disorders,” explains Doctoral Researcher Keshav Thapa.
Melanocortins are a family of hormones which regulate essential processes like energy balance, immune responses, and pigmentation. While MC1R is best known for its role in determining skin and hair color, its function in the liver had remained largely unexplored. Thapa’s research filled this gap in knowledge by revealing that MC1R is not only active in liver cells but also plays a crucial role in maintaining the delicate balance required for metabolic health.
The study revealed that the expression of MC1R in the liver is reduced in metabolic stress conditions like metabolic dysfunction-associated steatotic liver disease (MASLD).
Furthermore, when MC1R activity is disrupted, it has a serious impact on liver health. Thapa found in his research that genetic deficiency of MC1R led to higher cholesterol levels in the blood circulation and promoted accumulation of fat in the liver, thus increasing the susceptibility for developing steatotic liver disease. In contrast, pharmacological activation of MC1R in liver cells significantly reduced cellular cholesterol levels and enhanced the uptake of fat-carrying lipoproteins, which could serve as mechanism to lower blood cholesterol level.
“These findings highlight the critical role MC1R in protecting the liver against excess lipid accumulation and in maintaining the body’s overall metabolic balance,” Thapa explains.
This discovery holds profound implications for addressing the rapidly growing prevalence of metabolic liver disease like MASLD, which affects an estimated 25% of the global population.
“This condition, if left untreated, can ultimately lead to severe complications such as cirrhosis or cancer, highlighting unmet medical need for developing new and innovative treatments for the disease. By identifying MC1R as a key regulator of liver metabolism, this research implicates MC1R as a potential new therapeutic target that could address the root causes of MASLD and halt disease progression,” says Thapa.
This discovery also highlights the multifaceted role of MC1R by showing how a receptor known for its role in pigmentation also plays a crucial role in metabolic health.
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MSc Keshav Thapa defends the dissertation in Pharmacology titled “The Role of Melanocortin 1 Receptor in the Regulation of Cholesterol and Fatty Acid Metabolism in the Liver” at the University of Turku on 13 December 2024 at 12.00 (University of Turku, Medisiina C, Osmo Järvi auditorium, Kiinamyllynkatu 10, Turku).
The audience can participate in the defence also through remote access. (Meeting ID: 694 1369 0910, passcode: 257492)
Opponent: Professor Jukka Hakkola (University of Oulu)
Custos: Professor Eriika Savontaus (University of Turku)
> Doctoral Dissertation at UTUPub
Contact information: kekuth@utu.fi
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