The fat-busting molecule, leptin, appears to work in different regions of the brain in young compared with old mice.
In the mid 90’s, the way scientists think about what causes obesity was revolutionized with the discovery of leptin, an appetite-suppressing hormone.
Leptin is made by fat tissue and binds receptors in the brain to reduce energy intake by suppressing appetite and increasing activity to burn off energy, essentially regulating energy balance, or ‘homeostasis’.
Understanding how energy homeostasis is regulated is an area of intense research because of the current obesity epidemic. Importantly, childhood obesity is rising worldwide, together with associated conditions such as type 2 diabetes and heart disease. However, ways of treating childhood obesity remain mainly ineffective.
Leptin contributes to the regulation of energy homeostasis by acting on neurons in different brain regions, but exactly what effects each region mediates has not been clearly determined.
To address this question, Ring and Zeltser from Columbia University in New York, created mice in which leptin signaling was disrupted in only the hypothalamus of the brain (LeprNkx2.1 KO mice). When they compared the characteristics of these mice at a young age (<8 weeks) to mice lacking leptin signaling in all body cells (Leprdb/db mice), they found they were similar showing increased weight gain and increased amount of fat tissue. In contrast, after 8 weeks they found that mice with disrupted leptin signaling in the hypothalamus maintained consistent levels of fat tissue, whereas the mice lacking leptin in all body cells, became more and more obese. These findings suggest that leptin signaling in the mouse hypothalamus is needed to stop the development of fat tissue in young mice, whereas leptin signaling limits the development of fat tissue in older mice occurs through other regions of the brain.
The authors highlight that ‘these observations are consistent with the idea that the regulation of phenotypes related to energy homeostasis may be different (and less complex) in immature animals.’
The authors conclude ‘If this notion proves true, manipulations of critical components of circuits that establish metabolic profiles in young animals would represent a promising strategy to combat childhood obesity.’