Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis

Hypothalamic CLK2 activity is regulated by refeeding, insulin, and leptin.

• Reduction of CLK2 expression in the hypothalamus abolishes the appetite-suppressing effects of insulin and leptin.
• Chronic inhibition of CLK2 leads to increased body weight, fat mass, and food intake, along with decreased energy expenditure in mice on a regular diet.
• Impaired CLK2 phosphorylation in response to insulin, leptin, or refeeding is observed in mice on a high-fat diet and in db/db mice.
• Chronic CLK2 inhibition is associated with slight increases in fasting blood glucose levels and reduced liver expression of an enzyme involved in glucose production.
• Overexpressing CLK2 in the hypothalamus partially reverses obesity in mice on a high-fat diet or in db/db mice.

AI simplified