Genetic variance contributes to ingestive processes: A survey of mercaptoacetate-induced feeding in eleven inbred and one outbred mouse strains.
The feeding response following administration of the free fatty acid oxidation inhibitor, mercaptoacetate (MA) is conceptualized as an experimental model of lipoprivation, which may contribute to the understanding of inter-individual differences in the modulation of this homeostatic response. Although variation in the intake of food, water and glucoprivation as well as intake of several nutrients is known to be associated with genetic variation, it is not known whether MA-induced feeding is similarly dependent upon genotype. The present study therefore examined MA-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective MA doses (5, 35, 70, 100 mg/kg) and test times (1-4 h). MA produced significant dose-dependent and strain-dependent increases in food intake with strong responses noted in DBA/2J, outbred CD-1 and AKR/J mice. More limited dose-specific increases in food intake following MA occurred in C3H/HeJ, BALB/cJ, CBA/J, SJL/J, SWR/J and C57BL/6J mice. In contrast, MA failed to significantly increase food intake in A/J, C57BL/10J and 129P/3J mice. MA-induced food intake correlated significantly across strains only following the two highest doses, and intake following only the highest MA dose correlated significantly across strains with intake following only a moderate glucoprivic dose of 2-deoxy-d-glucose. Thus, these inter-strain differences suggest that lipoprivic (e.g., MA intake) and glucoprivic (e.g., 2-deoxy-d-glucose intake) responsivity operate via only partially overlapping genetic mechanisms of action. The demonstration of genotype-dependent variability in this lipoprivic response may provide the basis for the subsequent identification of trait-relevant genes.
Lewis
Sarah R
SR
Neuropsychology Doctoral Sub-Program and Department of Psychology, City University of New York, USA.
Dym
Cheryl
C
Ginzberg
Miriam
M
Kest
Benjamin
B
Bodnar
Richard J
RJ
D000818:Animals; D000963:Antimetabolites; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000235:genetics*; D005838:Genotype; D005947:Glucose / Q000172:deficiency; D051379:Mice; D013045:Species Specificity; D013864:Thioglycolates / Q000494:pharmacology*
D000963:Antimetabolites; D013864:Thioglycolates; C017487:2-mercaptoacetate; D003847:Deoxyglucose; D005947:Glucose