Fatty acid-binding proteins 5 and 7 gene deletion increases sucrose consumption and diminishes forced swim immobility time

Abstract

Inhibition and genetic deletion of fatty acid-binding proteins (FABPs) 5 and 7 have been shown to increase the levels of the endocannabinoid anandamide as well as the related N-acylethanolamine's palmitoylethanolamide and oleoylethanolamide. This study examined the role of these FABPs on forced-swim (FS) behavior and on sucrose consumption in two experiments: (experiment 1) using wild-type (WT) mice treated with the FABP inhibitor SBFI26 or vehicle and (experiment 2) using WT and FABP5/7 deficient mice. Results from experiment 1 showed that acute treatment with SBFI26 did not have any effect on sucrose intake or FS behavior in mice. In experiment 2, male and female FABP5/7 deficient mice showed significant increases in sucrose consumption (25 and 21%, respectively) compared with their WT counterparts. In addition, immobility time during the FS was decreased by 27% in both male and female FABP5/7 knockout mice compared with their WT counterparts. The fact that such differences were seen between the acute pharmacological approach and the genetic approach (gene deletion) of FABP needs to be further investigated. The function of FABPs and their specific effects on endocannabinoid anandamide, oleoylethanolamide, and palmitoylethanolamide may play an important role in the development of reward and mood behaviors and could provide opportunities for potential therapeutic targets.

Fatty acid-binding protein 5 differentially impacts dopamine signaling independent of sex and environment

“…In summary, given that there are noted neurochemical changes reported in the present study as well as behavioral differences in FABP5-deficient mice in related cognitive/addiction disease-modeling studies [ 1 , 4 – 6 , 9 , 72 ], and there is an existing modulatory relationship between endocannabinoid signaling and DA content within the midbrain [ 3 , 58 ], further research is needed to investigate FABP5’s neuropathophysiological role in shaping DA circuits.…”

“…The epidermal/brain FABP type 5 (FABP5) has been specifically implicated in the cellular uptake of the central endocannabinoid neurotransmitter, anandamide, as well as its hydrolysis into arachidonic acid [ 1 , 2 ] and, finally, its transportation to the nucleus where multiple cellular cascades take place—some of which subsequently alter behavior and dopaminergic functioning [ 3 ]. Recent pre-clinical studies have investigated FABP5 in the context of various dopamine (DA)-linked neuropathophysiological phenotypes; these include studies on depression-, anxiety-, and drug addiction-like behaviors [ 4 – 7 ] as well as neurochemical changes relating to memory functioning, stress, pain sensation, and neuroinflammation [ 5 , 8 – 11 ].…”

“…The DA system is well known to be associated with the neuromodulation of depression- and addiction-like phenotypes [ 12 – 16 ]. Hamilton and colleagues showed that transgenic FABP5−/− (knockout) mice significantly increased sucrose consumption and reduced immobility times in the forced-swim test compared with their wild-type counterparts [ 4 ]. In related behavioral evidence, pharmacological administration of DA type 2 (D2) agonists has been shown to reduce immobility time in the forced swim test, indicating that greater D2 activation exerts an antidepressant effect [ 17 ].…”

“…In two similar studies, antagonism of DA type 1 (D1) or D2 in the nucleus accumbens selectively decreased sucrose cue-evoked excitation, predicted the animal’s movement, and preceded their movement onset [ 18 ]; additionally, antagonism of D2 has been shown to decrease intake of sucrose as a function of its concentration [ 19 ]. Therefore, dopamine signaling is important for both reward-seeking behavior and orosensory stimulation of sucrose, and the FABP5 gene has been implicated in these DA-linked behaviors of consuming/seeking rewarding sucrose [ 15 , 20 ] and mediating immobility time in the forced swim test [ 4 , 17 , 21 ].…”

Full transcriptome analysis of gene expression in liver of mice in a comparative study of quercetin efficiency on two obesity models

“…Регулируемая при участии SREBP-1a (sterol regulatory element-binding protein 1) Acss2 способствует увеличению жировых запасов и отягощению ожирения [30]. Кодируемый Fabp5 переносчик жирных кислот препятствует апоптозу адипоцитов [31] посредством системы эндоканнабиноидов и GIP, повышает потребление пищи и на высококалорийных рационах, чем способствует развитию диет-индуцированного ожирения [32,33]. Характерно, что у мышей db/db контрольной группы экспрессия обоих этих генов была, по-видимому, изначально повышена по сравнению с контрольными C57Bl/6J.…”