Research
Hormonal
Mutations in the leptin-melanocortin pathway genes (LEP, LEPR, POMC, PCSK1, MC4R) cause severe, early-onset obesity through hyperphagia and altered energy expenditure.
If you have severe early-onset obesity, ask your doctor about genetic testing. For some, specific medications (like leptin therapy) can be highly effective because they target the root biological cause.
StrongSupportsHIGH confidence
Studying extreme obesity from single gene mutations has provided valuable information on the role of leptin–melanocortin pathway in energy balance.
Why this rating
Based on well-established monogenic obesity cases and clinical trials of leptin therapy.
Source
Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity
Marie Pigeyre et al. · Clinical Science · 2016
DOI 10.1042/cs20160136
narrative_reviewCited 402×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Obesity is a complex, heritable disorder resulting from the interplay of genetic susceptibility, epigenetics, metagenomics, and environmental factors, rather than solely lifestyle choices.Strong
- Polygenic obesity is influenced by hundreds of genetic variants affecting various biological pathways, including the central nervous system, adipocyte differentiation, and gut microbiota.Good
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