Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus

Abstract

Aim Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals. Methods Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high‐fat/high‐sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin‐injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus. Results Appetite‐stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c‐Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus. Conclusion Hedonically‐loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus.

Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats

“…7,15 Activation of galanin receptor subtype 2 in the lateral hypothalamus reinstated blunted leptin sensitivity during hedonic overeating of palatable foods in lean animals. 24 The results in the present study showed that administration of both hormones compromised their effects on food intake and bodyweight. The combined roles of both hormones were lower than galanin, but higher than leptin.…”

From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators

“…In addition to metabolic needs, the hedonic effects of food can also induce food intake in individuals, which may be because eating food can make them feel better and relieve stress [57]. Studies have demonstrated that leptin and ghrelin are responsible for both homeostatic and hedonic aspects of feeding by regulating dopamine signaling [57][58][59][60]. Overall, these results show that the gut microbiota may regulate feed intake by regulating leptinrelated signaling pathways.…”

High-Fat Diet Induces Pre-Diabetes and Distinct Sex-Specific Metabolic Alterations in Negr1-Deficient Mice

“…The food preference test was performed with minor modifications as described earlier in Leidmaa et al [ 34 ]. All the mice were housed in single cages and, on days 1–3, mice received regular food.…”