Galanin type 1 receptor knockout mice show altered responses to high-fat diet and glucose challenge.
Galanin, a brain and pancreatic peptide with three receptor subtypes (GALR1, GALR2, and GALR3), is hypothesized to participate in energy homeostasis and glucoregulation. Hypothalamic galanin expression is induced by dietary fat, and intra-hypothalamic galanin administration has orexigenic/anabolic properties. Systemic galanin infusion alters glucoregulation in non-human species, partly through direct actions on pancreatic islets. However, the physiologic significance of endogenous galanin-GALR signaling is unclear. The present studies tested the hypotheses that GALR1 deficiency alters food intake and feed efficiency following switches to high-fat diet and that GALR1 deficiency alters whole-body glucose homeostasis. Adult, male GALR1 knockout (-/-), heterozygote (+/-), and C57BL/6J control (+/+) mice were studied. GALR1 deficiency impaired adaptation to a 3-day high-fat diet challenge, leading to increased food intake, feed efficiency and weight gain. However, during the following 2 weeks, GALR1 knockout mice decreased intake, consuming less daily energy than while maintained on low-fat diet and also than heterozygote littermates. Chow-maintained GALR1 knockout mice showed relative hyperglycemia in fed and d-glucose (i.p. 1.5 g/kg)-challenged states. GALR1 knockout mice showed normal food intake, feed efficiency and weight accrual on low-fat diets, normal fasted glucose levels, and normal glucose sensitivity to porcine insulin (i.p. 1 IU/kg) in vivo. The results support the hypotheses that galanin-GALR1 systems help adapt food intake and metabolism to changes in dietary fat and modulate glucose disposition in mice.
Zorrilla
E P
EP
The Harold L Dorris Neurological Research Center, The Scripps Research Institute, La Jolla, CA 92037, USA. ezorrilla@scripps.edu
Brennan
M
M
Sabino
V
V
Lu
X
X
Bartfai
T
T
D000222:Adaptation, Physiological; D000704:Analysis of Variance; D000821:Animal Feed; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005951:Glucose Tolerance Test; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044091:Receptor, Galanin, Type 1 / Q000235:genetics / Q000502:physiology*; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D004041:Dietary Fats; D044091:Receptor, Galanin, Type 1