Metabolic Association between Leptin and the Corticotropin Releasing Hormone

Abstract

Results and Conclusion: The available data indicate that CRH exerts a role in the regulation of leptin in human adipocytes. We show that CRH downregulates leptin production by mature adipocytes and that a strong negative correlation exists between CRH and leptin levels in the periphery, and suggest the possible mechanisms of CRH control of leptin. Delineation of CRH control of leptin production by adipocytes may explain unknown pathogenic mechanisms linking stress and metabolism. Methods: In this article, we summarized the salient information on leptin and CRH in relation to metabolism. We also investigated the direct effect of recombinant CRH on leptin secretion by primary cultures of human adipocytes isolated from subcutaneous abdominal adipose tissue of 7 healthy children and adolescents, and measured CRH and leptin levels in plasma collected from peripheral blood of 24 healthy children and adolescents to assess whether a correlation exists between CRH and leptin levels in the periphery. Objective: In healthy individuals, leptin is produced from adipose tissue and is secreted into the circulation to communicate energy balance status to the brain and control fat metabolism. Corticotropin- Releasing Hormone (CRH) is synthesized in the hypothalamus and regulates stress responses. Among the many adipokines and hormones that control fat metabolism, leptin and CRH both curb appetite and inhibit food intake. Despite numerous reports on leptin and CRH properties and function, little has been actually shown about their association in the adipose tissue environment.

Macrophage‐activating lipopeptide‐2 and corticotropin‐releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl‐CoA desaturase and fatty acid desaturase 2

“…6,12 Interestingly, exogenous CRH enters the cytoplasm of human sebocytes rapidly and builds up high intracellular concentrations, a finding which is compatible with the quick speed of CRH-induced neuron responses to stress. 37 On the other hand, CRH downregulates leptin production by mature adipocytes, 38 whereas leptin promotes a pro-inflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes. 34 These findings indicate that CRH exhibits a stress-associated catabolic activity on human lipogenic cells.…”

Leptin in Human Milk—One of the Key Regulators of Nutritional Programming

“…These receptors, like the leptin receptor, bind to Janus kinase (JAK) and phosphorylate tyrosine on the cytoplasmic portion of the receptor, to which STAT 3 (signal transducer and activator of transcription 3) is recruited (Heinrich et al, 2002). The concentration of leptin in serum is directly proportional to the amount of white adipose tissue (WAT) or food intake [ 11 , 12 ].…”

“…Studies on animal models and in obese individuals show an increase in leptin concentration in circulation [ 12 , 22 ]. This may be related to the insensitivity of leptin receptors, reduced receptor expression or hampered signal transduction in the hypothalamus.…”

“…Resistance to leptin, impairment of the regulatory outflow of leptin and increased food intake contribute to the impairment of energy homeostasis, which exacerbates the problem of obesity and has serious consequences for the whole body. The reason for this situation is complex and has not been fully understood yet [ 12 , 17 ]. Leptin is secreted in a pulsatile diurnal rhythm, with a peak at night.…”

Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player

“…This sequence is mediated by binding to melanocortin receptor 2 (MC2R), stimulation of the membrane-bound adenylate cyclase and calcium influx [ 18 , 19 ]. With the emerging evidence showing the expression of MC2R in tissues other than adrenal cortex, recent literature have shed light on new roles of ACTH, including lipolytic activity in adipocytes [ 20 ], reducing lipid content of cells by knockdown of MC2R and inhibition of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) [ 21 ], suppressing leptin expression [ 22 ], playing a role in the differentiation of mesenchymal cells [ 23 ], regulation of bone mass [ 24 ], a role in the maintenance and repair of the vascular extracellular matrix [ 25 ], controlling thymocyte homeostasis [ 26 ], and amelioration of tumor necrosis factor (TNF)-induced acute kidney injury [ 27 ].…”