Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications

Abstract

Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications

“…Signal Transducer and Activator of Transcription 3 (STAT-3) is a substrate of JAK 2 and subsequently binds to the phosphorylated Tyr 1138 . STAT-3 then undergoes dimerization and translocates into the cell nucleus to function as a promoter for gene transcription [4]. Members of the SOCS family (SOCS1 and SOCS3) suppress the action of leptin by binding to JAK 2 and tyrosine residues.…”

“…Leptin is a cytokine produced predominantly by the differentiated white adipose tissue, with various func tions in the immune and endocrine systems, including reproduction, glucose homeostasis, hematopoiesis, an giogenesis, osteogenesis, wound healing, and inflam mation (4). This hormone regulates caloric expenditure and intake, playing a central action in energy balance (5).…”

The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels

“…These receptors are expressed in the brain and in peripheral tissues. 63 In the hypothalamus leptin acts as an anorexigenic hormone regulating the melanocortine/neuropeptide Y system to reduce food intake, increase energy expenditure, and decrease body weight. 64 However, circulating leptin levels are increased in obese humans, 65 suggesting that obesity may be either a result or a cause of leptin resistance.…”

Reply

“…The authors did not mention the above diseases, and this omission could have influenced the findings of the study. In addition to confounding diseases, it has been suggested that some types of antidepressants, antipsychotics, glucocorticoids, antihypertensive drugs, and statins affect serum leptin levels (5,6). Also, dietary supplements, such as linoleic acid, zinc, vitamin A, vitamin D, vitamin E, and -3 fatty acid, could affect plasma leptin levels (7,8).…”