Orexin neuropetides: Physiology and significance in food metabolism

Shikha Jain, Ajay K Jain

Astrocyte 2016 3(3):148-152

Orexin is a neuropeptide secreted by a group of hypothalamic neurons. Orexin neurons in hypothalamus have widespread projections throughout the brain and peripheral structures. Orexin actions are mediated by calcium and raise cytoplasmic Ca+2 via a mechanism based on G-protein. Orexin activity is modulated by the biological clock. Orexin-A influences the hypothalamic and pituitary hormone release along with a role in arousal, energy homeostasis, goal-orientated behavior, and autonomic nervous system control. Orexin neurons receive indirect circadian signals that integrate with metabolic signals to regulate energy homeostasis. The metabolism of carbohydrates and fats is also linked to orexin. Orexin-A increases metabolic rate; insulin-induced hypoglycemia activates orexin-containing neurons, thus orexins regulate energy metabolism. The orexin-induced increase in energy metabolism is not simply due to increased wakefulness and physical activity but orexin increases metabolism independent of sleep/wake, locomotion, and food intake. Thus, orexin appears to be an essential factor for maintaining energy balance and body weight. Excess energy intake and decreased energy consumption due to sedentary lifestyle are the main contributors to the metabolic syndrome epidemic, and whether there is any correlation of metabolic risk markers with orexin levels is yet to be established. Orexin efficiently protects against the development of peripheral insulin resistance induced by ageing or high-fat feeding. Hyperglycemia caused by insulin insensitivity during ageing or by consumption of a high-fat diet leads to reduction in orexin expression in hypothalamus, which further exacerbates peripheral insulin resistance. Therefore, orexin receptor controlling hypothalamic insulin/leptin actions may be a new target for future treatment of hyperglycemia in patients with type 2 diabetes.

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