Effects of chronic mild food restriction on behavior and the hypothalamic malonyl‐CoA signaling pathway

Abstract

Depression induces anorexia, leading to suppressed feeding behaviors and energy intake. Previously, we revealed that chronic social defeat induced a mild suppression of feeding in rats with elevated levels of hypothalamic malonyl-CoA which regulates feeding. Therefore, we attempted to elucidate the effects of chronic mild food restriction on behavior and on hypothalamic malonyl-CoA. The chronic mild food restricted rats were fed a restricted diet approximately 80% to 90% amount of diet compared to the control for 5 weeks. Ratios of restriction were adjusted with feed consumption in the chronic social defeat stressed rats. Chronic mild food restricted rats exhibited a suppression of body weight gain similar to that of the chronic social defeat stressed rats. Also these rats showed increased time spent in the center area of an open field (OF), prolonged immobility time in forced swim, increased phosphorylation of hypothalamic adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase and a decreased concentration of hypothalamic malonyl-CoA. Weight of the adrenal glands, locomotion in an OF, mitogen-activated protein kinase cascade and calcium/calmodulin-dependent protein kinases II in the hippocampus were not affected by chronic mild food restriction. Our findings suggest that chronic mild food restriction activates AMPK following a decreased hypothalamic malonyl-CoA.

Alterations of proteome, mitochondrial dynamic and autophagy in the hypothalamus during activity-based anorexia

“…Similarly, increased hypothalamic energy and mitochondrial metabolism may be the consequence of food anticipatory activity. In the same way, we observed that AMPK was less activated in the hypothalamus of LFA and ABA mice while other studies previously showed activation of AMPK after food deprivation 50 , 51 . However, hypothalamic AMPK can be affected by stress, i.e.…”

Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging

“…Some of the largest consumers of NADPH include the enzymes for the biosynthesis of fatty acids, cholesterol, steroids, and deoxyribonucleotides [48]. During CR, AMP kinase (AMPK) becomes activated [254], prominently in the hypothalamus [255]. AMPK phosphorylates acetyl-CoA carboxylase to inhibit fatty acid synthesis [255].…”

“…During CR, AMP kinase (AMPK) becomes activated [254], prominently in the hypothalamus [255]. AMPK phosphorylates acetyl-CoA carboxylase to inhibit fatty acid synthesis [255]. This inhibition of fatty acid synthesis leads to the activation of fatty acid beta-oxidation (except in neurons that lack these enzymes) to provide cellular energy and prevent a futile cycle of fatty acid synthesis and breakdown.…”

Effect of caloric restriction on depression

“…Interestingly, reducing the number of calories consumed promotes the survival of newly generated cells in the hippocampus [36,37]. Furthermore, chronic mild food restriction activates AMPK following decreased hypothalamic malonyl-CoA, an inhibitor of fatty acid oxidation [38].…”