title: High-fat diet induces apoptosis of hypothalamic neurons.
abstract: Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity.
authors.affiliation: Department of Internal Medicine, University of Campinas, Campinas, Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Moraes
authors.forename: Andressa
authors.initials: A
authors.lastname: Coope
authors.forename: Joseane
authors.initials: J
authors.lastname: Morari
authors.forename: Dennys E
authors.initials: DE
authors.lastname: Cintra
authors.forename: Erika A
authors.initials: EA
authors.lastname: Roman
authors.forename: José R
authors.initials: JR
authors.lastname: Pauli
authors.forename: Talita
authors.initials: T
authors.lastname: Romanatto
authors.forename: José B
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Alexandre L R
authors.initials: AL
authors.lastname: Oliveira
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Saad
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso