Understanding a root cause

Genetic variants in neurosignaling pathways in the hypothalamus may be responsible for body weight

Some rare forms of obesity are caused by genetic variants in a key neurosignaling pathway in the hypothalamus responsible for regulating hunger, food intake, satiety, and energy expenditure. This can influence body weight. This pathway is called the melanocortin-4 receptor pathway (MC4R pathway).

Impaired MC4R signaling can lead to early-onset, severe obesity and hyperphagia, irrespective of environmental and lifestyle factors.1,2

Explore the science

Genetic variants in neurosignaling pathways in the hypothalamus may be responsible for body weight

Your practice likely includes possible patients

While each specific variant may be rare, collectively they are not. A portion of the approximately 5 million individuals in the US who experience early-onset, severe obesity3* could also be experiencing hyperphagia4 due to genetic variants associated with MC4R pathway impairment.

More than 80 genes associated with obesity have been identified to date.6 Of these genes, multiple genetic variants lead to MC4R pathway impairment.

Individuals with these genetic variants may not respond to traditional interventions for general obesity, as the likely underlying pathology is not targeted by these approaches.1

*1.8% of the US population (328M; 2019 US census) presents with early-onset, severe obesity3

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5 Million

Approximately 5 million individuals in the US experience early-onset, severe obesity, and a portion of them may also experience hyperphagia3,4*

94 %

of individuals with early-onset, severe obesity continue to have obesity into adulthood5

Recognizing the signs

Rare genetic variants along the MC4R pathway may lead to diseases that cause hyperphagia and early-onset obesity. These hallmark symptoms could be indicative of rare genetic diseases of obesity.1

Nate, an active young boy, living with POMC

Nate, living with POMC Heterozygous deficiency

Genetic testing is recommended for patients with these clinical features, as testing can aid in diagnosis and help inform appropriate interventions and treatment eligibility.7,8
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LEPR=leptin receptor; PCSK1=proprotein convertase subtilisin/kexin type 1; POMC=proopiomelanocortin.

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