Brain-Derived Neurotrophic Factor Plays a Role as an Anorexigenic Factor in the Dorsal Vagal Complex

Abstract

Brain-derived neurotrophic factor (BDNF) has recently been implicated as an anorexigenic factor in the central control of food intake. Previous studies focused on the hypothalamus as a probable site of action for this neurotrophin. It was demonstrated that BDNF is an important downstream effector of melanocortin signaling in the ventromedial hypothalamus. In this study, we addressed whether BDNF can modulate food intake in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). To this end, we used two complementary methodological approaches in adult rats. First, we measured the effects of intraparenchymal infusions of exogenous BDNF within the DVC on food intake and body weight. Second, we measured the endogenous BDNF protein content in the DVC and hypothalamus after food deprivation, refeeding, or peripheral treatments by the anorexigenic hormones leptin and cholecystokinin (CCK). BDNF infusion within the DVC induced anorexia and weight loss. In the DVC, BDNF protein content decreased after 48 h food deprivation and increased after refeeding. Acute and repetitive peripheral leptin injections induced an increase of the BDNF protein content within the DVC. Moreover, peripheral CCK treatment induced a transient increase of BDNF protein content first in the DVC (30 min after CCK) and later on in the hypothalamus (2 h after CCK). Taken together, these results strongly support the view that BDNF plays a role as an anorexigenic factor in the DVC. Our data also suggest that BDNF may constitute a common downstream effector of leptin and CCK, possibly involved in their synergistic action.

Selective Deletion ofBdnfin the Ventromedial and Dorsomedial Hypothalamus of Adult Mice Results in Hyperphagic Behavior and Obesity

“…Selectively deleting Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and body weight gain BDNF is expressed in various energy balance-regulating centers in the hypothalamus and hindbrain in the developing and mature brain (Conner et al, 1997;Sugiyama et al, 2003;Tran et al, 2003;Xu et al, 2003;Bariohay et al, 2005). Mouse models of global or central depletion of BDNF and TrkB exhibit increases in food intake and dramatic obesity (Lyons et al, 1999;Kernie et al, 2000;Rios et al, 2001;Xu et al, 2003).…”

“…BDNF is expressed in several energy balance centers in the hypothalamus and hindbrain in the developing and mature brain (Conner et al, 1997;Sugiyama et al, 2003;Tran et al, 2003;Bariohay et al, 2005). Within the hypothalamus, it is most abundant in the ventromedial hypothalamus (VMH), a critical subpopulation of neurons important for the regulation of food intake.…”

“…For example, infusion of BDNF into the brain of mature rats significantly reduces food intake (Lapchak and Hefti, 1992). Additionally, BDNF mRNA levels are reduced by fasting in the VMH and nucleus of the solitary tract Bariohay et al, 2005;Tran et al, 2006). BDNF expression in these regions is also regulated by the peripheral satiety factors leptin and cholecystokinin (Bariohay et al, 2005;Komori et al, 2006).…”

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

“…Chronic, intermittent subcutaneous injections of BDNF reduced body weight (81), suggesting peripheral sites of action for BDNF, as a molecule of this size (13.6 kDa) cannot cross the blood-brain barrier (59,60). In a recent study in which the dorsal vagal complex was specifically targeted, chronic administration of BDNF significantly decreased feeding and body weight gain at doses of 0.1 and 1.0 g (3). Because these studies relied on a chronic infusion method, the time course of BDNF anorectic effects is unknown.…”

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

“…Intraparenchymal administration of BDNF into the ventromedial nucleus and paraventricular nucleus of the hypothalamus reduces food intake and increases energy expenditure (23)(24)(25)(26)(27)(28). Similarly, delivery of BDNF directly into the dorsal vagal complex (29,30) or nucleus tractus solitarius (31) of the hindbrain reduces food intake and increases energy expenditure.…”