Failure of the feeding response to fasting in carnitine-deficient juvenile visceral steatosis (JVS) mice: Involvement of defective acyl-ghrelin secretion and enhanced corticotropin-releasing factor signaling in the hypothalamus

Abstract

Carnitine-deficient juvenile visceral steatosis (JVS) mice, suffering from fatty acid metabolism abnormalities, have reduced locomotor activity after fasting. We examined whether JVS mice exhibit specific defect in the feeding response to fasting, a key process of anti-famine homeostatic mechanism. Carnitine-deficient JVS mice showed grossly defective feeding response to 24 h-fasting, with almost no food intake in the first 4 h, in marked contrast to control animals. JVS mice also showed defective acyl-ghrelin response to fasting, less suppressed leptin, and seemingly normal corticotropin-releasing factor (CRF) expression in the hypothalamus despite markedly increased plasma corticosterone. The anorectic response was ameliorated by intraperitoneal administration of carnitine or acyl-ghrelin, with decreased CRF expression. Intracerebroventricular treatment of CRF type 2 receptor antagonist, anti-sauvagine-30, recovered the defective feeding response of 24 h-fasted JVS mice. The defective feeding response to fasting in carnitine-deficient JVS mice is due to the defective acyl-ghrelin and enhanced CRF signaling in the hypothalamus through fatty acid metabolism abnormalities. In this animal model, carnitine normalizes the feeding response through an inhibition of CRF.

Voluntary exercise under a food restriction condition decreases blood branched-chain amino acid levels, in addition to improvement of glucose and lipid metabolism, in db mice, animal model of type 2 diabetes

“…The underlying mechanism regarding the influence of exercise on blood adiponectin and leptin levels will be elucidated by this animal model. Regarding alterations of plasma corticosterone levels, fasting has been reported to increase plasma corticosterone [38,39]. Interestingly, VE in the present study decreased plasma corticosterone in db mice, suggesting that the effects of exercise are not explained by the effects of longer fasting in association with increased energy expenditure.…”

Food Intake and Core Body Temperature of Pups and Adults in adbMouse Line Deficient in the Long Form of the Leptin Receptor withoutMistyMutation

“…Mice were then euthanized by cervical dislocation, and the brain, heart, liver, white adipose tissue (WAT, fat surrounding epididymis), and BAT were removed, blotted, weighed, and frozen immediately in liquid nitrogen. The hypothalamic block was separated from the brain [27]. The plasma and frozen organs were stored at −80°C until analysis.…”