Abstract
Obesity/overweight are important health problems due to metabolic complications. Dysregulation of peptides exerting orexigenic/anorexigenic effects must be investigated in-depth to understand the mechanisms involved in feeding behaviour. One of the most important and studied orexigenic peptides is galanin (GAL). The aim of this review is to update the mechanisms of action and physiological roles played by the GAL family of peptides (GAL, GAL-like peptide, GAL message-associated peptide, alarin) in the control of food intake and to review the involvement of these peptides in metabolic diseases and food intake disorders in experimental animal models and humans. The interaction between GAL and NPY in feeding and energy metabolism, the relationships between GAL and other substances involved in food intake mechanisms, the potential pharmacological strategies to treat food intake disorders and obesity and the possible clinical applications will be mentioned and discussed. Some research lines are suggested to be developed in the future, such as studies focused on GAL receptor/neuropeptide Y Y1 receptor interactions in hypothalamic and extra-hypothalamic nuclei and sexual differences regarding the expression of GAL in feeding behaviour. It is also important to study the possible GAL resistance in obese individuals to better understand the molecular mechanisms by which GAL regulates insulin/glucose metabolism. GAL does not exert a pivotal role in weight regulation and food intake, but this role is crucial in fat intake and also exerts an important action by regulating the activity of other key compounds under conditions of stress/altered diet.
Highlights
The disturbance in the balance between energy intake and energy requirements leads to changes in metabolism
- high fat diet: control animals gained more body weight than GAL-knockout animals - hedonically-loaded foods blocked the inhibitory actions of leptin on orexin neurons; GAL is a mediator of leptin action regulating nutrient reward by inhibiting orexin neurons - overeating palatable foods: decreased in lean mice by activating the GAL 2 receptor - administration of green tea extract: decreased food intake, body fat/weight, prevented fat accumulation, increased peripheral activity/expression of neprilysin - diet-induced obese animals treated with celastrol: decreased obesity, food/fat intake, induced weight Mouse models with mixed pathologies: - underweight animals with signs of anxiety, depression and anhedonia: GAL 2 receptor agonists normalized body weight/mood behaviours
New research lines must be developed to prevent/treat obesity and the dysregulation of peptides exerting an orexigenic or an anorexigenic effect must be investigated in-depth to understand the mechanisms involved in feeding behaviour
Summary
The disturbance in the balance between energy intake and energy requirements leads to changes in metabolism. A disbalance in the activity of these two subsets of neurons, which are connected to other brain regions, may lead to feeding alterations In this sense, a review has been focused on the development of the hypothalamic pathways regulating energy balance/food intake [5] and it has been reported that galanin (GAL), enkephalin, orexin, melanin-concentrating hormone and cannabonids are involved in fat intake; NPY and AgRP in carbohydrate intake, and growth hormone-releasing factor and ghrelin in protein intake [6].
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