Alteration in the number of neuronal and non-neuronal cells in mouse models of obesity

Obesity is defined as abnormal or excessive fat accumulation that may impair health and is a risk factor for developing other diseases, such as type 2 diabetes and cardiovascular disorder. Obesity is also associated with structural and functional alterations in the brain, and this condition has been shown to increase the risk of Alzheimer’s disease. However, while obesity has been associated with neurodegenerative processes, its impact on brain cell composition remains to be determined. In the current study, we used the isotropic fractionator method to determine the absolute composition of neuronal and non-neuronal cells in different brain regions of the genetic mouse models of obesity Lep(ob/ob) and LepR(Null/Null). Our results show that 10- to 12-month-old female Lep(ob/ob) and LepR(Null/Null) mice have reduced neuronal number and density in the hippocampus compared to C57BL/6 wild-type mice. Furthermore, LepR(Null/Null) mice have increased density of non-neuronal cells, mainly glial cells, in the hippocampus, frontal cortex and hypothalamus compared to wild-type or Lep(ob/ob) mice, indicating enhanced inflammatory responses in different brain regions of the LepR(Null/Null) model. Collectively, our findings suggest that obesity might cause changes in brain cell composition that are associated with neurodegenerative and inflammatory processes in different brain regions of female mice.