Effect on Energy balance and appetite
Leptin (from leptos Greek: thin) is a 16-kDa protein hormone that helps regulate hunger by regulating energy intake and expenditure. Leptins reduce appetite and are released after a meal when hunger and thirst have been satisfied. It’s one of the most essential hormones derived from adipose tissue. In humans, the Lep gene (also known as the ObLep gene; Ob stands for obesity, while Lep stands for leptin) is found on chromosome 7. Both neuropeptides (Leptins and Galanins) have an impact on the cerebral cortex areas that control higher-order decision-making. The secretion of adipose and stomach Leptins is coordinated to ensure proper meal digestion and energy storage.
Leptin is a pro-satiety peptide that is produced mostly by white adipocytes, but also by a variety of other tissues, including the heart. Although its main activities are dependent on the activation of the long form of the leptin receptor, known as OBRb, circulating leptin acts through specialized receptors. Leptin activates a complex neuronal circuit containing anorexigenic (appetite-suppressing) and orexigenic (appetite-stimulating) neuropeptides to modulate food intake via ObRb-receptor binding in the hypothalamus. Leptin interacts with the mesolimbic dopamine system, which is involved in feeding motivation and reward, and the nucleus of the solitary tract of the brainstem to contribute to satiety outside of the hypothalamus.
Effect on Mitochondria
Although leptin has no direct effect on mitochondrial integrity, it can enhance the propensity for calcium to produce mitochondrial swelling, which can be reduced in part by an OBR antagonist.
Effect on Neuroendocrine system
Leptin levels drop rapidly before and out of proportion to changes in fat mass in response to fasting, activating the neuroendocrine response to acute energy deprivation. In mice and humans, this response includes lower levels of reproductive hormones, which prevent pregnancy (an energy-intensive process), lower thyroid hormone levels, which slow metabolic rate, higher levels of growth hormone, which may mobilize energy stores, and lower levels of insulin-like growth factor-1 (IGF-1) which may slow growth-related processes. Because individuals with congenital leptin insufficiency have normal linear growth and adrenal function, unlike mice, the connections between leptin and the growth hormone and adrenal axis appear to be less relevant in humans than in animal models.
Leptin treatment has been demonstrated to improve not just hyperinsulinemia but also levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides in persons with congenital leptin insufficiency.
Leptins can operate directly and indirectly on TRH-secreting neurons, but only indirectly on GnRH-secreting neurons in the hypothalamus. In mice and humans, the effect of leptin on cortisol levels during hunger is different. Leptin administration does not alter the high ACTH levels associated with hunger in humans, unlike in normal mice.
Sources and references: The Role of Leptin in Human Physiology: Emerging Clinical Applications by Kelesidis et al. (2011)