Leptin as a Modulator of Neuroendocrine Function in Humans

Abstract

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2 lipodystrophic mice independent of hepatocyte leptin receptors

“…Elevated corticosterone appears to be a common fi nding in murine models of leptin defi ciency ( 59 ), possibly owing to lack of a direct suppressive effect of leptin on glucocorticoid secretion by corticoadrenal cells ( 60 ). Interestingly, whereas adrenalectomy dramatically improves both hyperglycemia and hyperinsulinemia in A-ZIP/F-1 lipodystrophic mice, it fails to reduce liver triglyceride concentrations in these animals ( 61 ), suggesting that hypercorticosteronemia does not play an essential role in the hepatic steatosis associated with severe lipodystrophy.…”

Adiponectin, Leptin and Objectively Measured Physical Activity in Adults: A Narrative Review

“…On the other hand, leptin is a peptide hormone secreted by adipose tissue which plays a central role in regulating human energy homeostasis (24,25). It has been proven that the level of leptin in blood serum is higher in the obese, in comparison with both adults and children of appropriate body mass.…”

Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1

“…Few studies have investigated the hormonal changes related to the return of the menstrual cycle [7,12]. Only one study observed the hormonal changes that occur at the time of menstrual cycle return [13], but this study did not emphasize IGF-1 levels.…”

“…The pulsatile secretion of this hypothalamic peptide accelerates in proportion to the stock of fat; in other words, the excessive loss of adipose tissue leads to the decreased production of leptin, which diminishes signals to the central nervous system, leading to a decrease in GnRH and a subsequent drop in LH and FSH levels. These changes consequently lead to hypogonadotropic hypogonadism [7,8,9]. …”