Why a broken protein makes mice eat less after fasting and get fat
Genetic Deletion of KLHL1 Leads to Hyperexcitability in Hypothalamic POMC Neurons and Lack of Electrical Responses to Leptin
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
A protein called KLHL1 normally keeps a brain channel called Cav3.1 in check. When KLHL1 is missing, Cav3.1 goes wild, making brain cells that tell you you're full fire nonstop—even when they shouldn't.
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Researchers compare people who have a condition (cases) with similar people who do not (controls), looking back in time for differences in exposure. Useful but more prone to bias.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
A protein called KLHL1 normally keeps a brain channel called Cav3.1 in check. When KLHL1 is missing, Cav3.1 goes wild, making brain cells that tell you you're full fire nonstop—even when they shouldn't.
Systematic Reviews & Meta-Analyses
Max 100Randomized Controlled Trials
Max 90Cohort Studies
Max 72Case-Control Studies
Max 58Cross-Sectional Studies
Max 44Case Reports & Case Series
Max 30Expert Opinion & Narrative Reviews
Max 517 / 58
Evidence Score
Researchers compare people who have a condition (cases) with similar people who do not (controls), looking back in time for differences in exposure. Useful but more prone to bias.
Publication
Authors
Perissinotti PP, Martínez-Hernández E, He Y, Koob MD, Piedras-Rentería ES
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Claims (10)
In mice, removing the KLHL1 gene increases CaV3.1 calcium channel levels in specific brain neurons that regulate energy balance, leading to higher baseline electrical activity and reduced response to the hormone leptin, resulting in obesity.
In mice lacking the KLHL1 gene, increased levels of CaV3.1 calcium channels in specific brain neurons lead to a 40% higher baseline calcium current, a shift in channel activation to more negative voltages, and a 2.3-fold increase in calcium entry at rest.
In mice lacking the KLHL1 gene, blocking T-type calcium channels with a specific drug restores the ability of leptin to activate brain cells that control appetite, showing that excessive electrical activity in these cells—not a broken leptin receptor—causes leptin resistance.
Mice without the KLHL1 gene develop obesity as adults and eat less in the first hour after being hungry, compared to normal mice, showing differences in how the hypothalamus controls hunger and fullness.
In mice lacking the KLHL1 gene, specific brain cells called POMC neurons fire more frequently and start at a higher electrical baseline, which makes them more active overall and prevents leptin from increasing their activity further.