Mice bearing Acads mutation display altered postingestive but not 5-s orosensory response to dietary fat

Abstract

. Mice bearing Acads mutation display altered postingestive but not 5-s orosensory response to dietary fat. Am J Physiol Regul Integr Comp Physiol 286: R311-R319, 2004. First published October 30, 2003 10.1152/ajpregu.00488.2003.-A previous survey of mouse inbred strains revealed a wide range in selfselected fat intake, from 26 to 83% of energy. The BALB/cByJ strain selected a lower percentage of fat intake (36%) than all other strains tested except for the CAST/Ei. BALB/cByJ mice are deficient in the short-chain acyl-CoA dehydrogenase (SCAD) enzyme due to a spontaneous mutation in Acads. We hypothesized that this deficiency would alter fat appetite and used three behavioral test paradigms to compare the response of BALB/cByKz.Acads Ϫ/Ϫ and BALB/ cByKz.Acads ϩ/ϩ mice to fat stimuli. First, during 10-day exposure to a macronutrient self-selection diet, Acads Ϫ/Ϫ mice consumed proportionately less fat and more carbohydrate than Acads ϩ/ϩ mice, yet total energy intake was similar between strains. Next, in 48-h two-bottle preference tests, Acads ϩ/ϩ mice displayed a preference for 50% corn oil, but Acads Ϫ/Ϫ mice did not. Finally, in brief-access taste tests employing successive 5-s presentations of corn oil in an ascending concentration series ending with 50%, there were no effects of strain on total licks, indicating that Acads does not alter acute orosensory response to this fat stimulus. With 15-s presentations, however, the Acads ϩ/ϩ mice licked more of the 50% oil than Acads Ϫ/Ϫ, suggesting orosensory effects related to the increased exposure time. In contrast to corn oil, there were no strain differences in licking response to sucrose solution in either the two-bottle or brief-access taste tests. The observation that SCAD-deficient mice display altered postingestive responses to dietary fat provides further evidence for the metabolic control of feeding. taste; ingestive behavior; licking frequency; diet selection IN A PHENOTYPIC SURVEY of mouse inbred strains, self-selected fat consumption ranged from 26 to 83% of total energy across strains in a choice paradigm containing separate sources of carbohydrate, fat, and protein (43). The BALB/cByJ mice selected a lower percentage of fat intake (36%) than all other strains tested with the exception of the CAST/Ei (25%) (43). The BALB/cByJ mouse strain bears a spontaneous deletion in the short-chain acyl-CoA dehydrogenase (SCAD) structural gene (Acads) (38, 51) that results in missplicing of the mRNA and the absence of functional SCAD (18; for review, see Refs. 38 and 52). SCAD is a mitochondrial enzyme that catalyzes the first reaction in the ␤-oxidation of C 4 -C 6 fatty acids. We hypothesized that this deficiency in ␤-oxidation of fatty acids may underlie the observed dietary preference.Fatty acid oxidation is thought to be a key factor in the metabolic control of food intake (10) because rodents are stimulated to eat after administration of inhibitors that interfere with ␤-oxidation of fatty acids (36-37). For example, administration of mercaptoacetate (MA) st...

Reinforcing effect for corn oil stimulus was concentration dependent in an operant task in mice

“…We used 0.3% xanthan gum and mineral oil as the representative vehicles for oil texture. The former is frequently used as a vehicle for oil preference tests (Ramirez, 1997;Smith Richards et al, 2004;Takeda et al, 2000), and mineral oil is a long-chain carbon hydride and is not absorbed from the gastrointestinal tract, so it has also been used as a vehicle for an oil preference test (Kawai and Fushiki, 2003;Yoneda et al, 2007). Mineral oil was reported to activate the oil-like texturesensitive neurons in the brain in the same way as some vegetable oils and silicone oil do (Rolls, 2005).…”

“…Furthermore, Ward and Dykstra used 3% xanthan gum as a diluent, which is too high a concentration to mimic the oil texture (Ramirez, 1994). Many researchers including us are using 0.2-0.3% xanthan gum to mimic the viscosity of oil (Freed and Green, 1998;Kawai and Fushiki, 2003;Smith Richards et al, 2004). Since oil-like texture itself is an adequate stimulus for palatability (Ackroff et al, 1990;Mindell et al, 1990), the vehicle should be carefully selected to assess the reinforcing effect of corn oil.…”

Brain Transcriptional Responses to High-Fat Diet in Acads-Deficient Mice Reveal Energy Sensing Pathways

“…A spontaneous deletion in the structural gene for Acads results in the complete absence of functional short-chain acyl-CoA dehydrogenase [5] in the BALB/cByJ mouse inbred strain. We have shown that Acads -deficiency [6]–[7] suppressed voluntary fat- but not carbohydrate intake in mice [8]. Specifically, Acads −/− mice shifted their food consumption away from fat and toward carbohydrate when offered a choice of diets, while total calorie intake remained unchanged.…”

“…We used microarray technology to compare the short-term effects of high- or low-fat diet on gene expression in the brain of Acads −/− and Acads+/+ mice. Tissues were harvested 2 d after initiating the experimental diets to coincide with the time-point at which fat avoidance begins [8]. We identified transcriptional responses to genotype and diet that that may be linked to feeding behavior in this model.…”

Physiological regulation of food intake

“…Lipolysis of triglycerides by lingual lipase secreted into the mouth was shown to contribute to the tasting of fatty acids (72). Mice deficient in short-chain acyl-CoA dehydrogenase were shown by two-bottle preference tests to have normal acute orosensory response to a fat stimulus but altered postingestive responses (38).…”