Leptin participation in the processes of nervous impulse transmission and its influence on the formation of neuro-mental development of children

Review of publications on the functional features of leptin in the central nervous system in children. The participation of leptin mechanisms in the transmission of nerve impulses, the effect of leptin on cognitive functions in children. The article reveals the general mechanisms of maturation of the central nervous system in children, the participation of leptin and leptin receptors in the formation of cognitive abilities in children. Possible interrelationships of impairments in cognitive development and lipid metabolism including obesity are revealed.

Relationship Between Circulating Metabolic Hormones and Their Central Receptors During Ovariectomy-Induced Weight Gain in Rats

Although increasing research focuses on the phenomenon of body weight gain in women after menopause, the complexity of body weight regulation and the array of models used to investigate it has proven to be challenging. Here, we used ovariectomized (OVX) rats, which rapidly gain weight, to determine if receptors for ghrelin, insulin, or leptin in the dorsal vagal complex (DVC), arcuate nucleus (ARC), or paraventricular nucleus (PVN) change during post-ovariectomy weight gain. Female Sprague-Dawley rats with ad libitum access to standard laboratory chow were bilaterally OVX or sham OVX. Subgroups were weighed and then terminated on day 5, 33, or 54 post-operatively; blood and brains were collected. ELISA kits were used to measure receptors for ghrelin, insulin, and leptin in the DVC, ARC, and PVN, as well as plasma ghrelin, insulin, and leptin. As expected, body weight increased rapidly after ovariectomy. However, ghrelin receptors did not change in any of the areas for either group, nor did circulating ghrelin. Thus, the receptor:hormone ratio indicated comparable ghrelin signaling in these CNS areas for both groups. Insulin receptors in the DVC and PVN decreased in the OVX group over time, increased in the PVN of the Sham group, and were unchanged in the ARC. These changes were accompanied by elevated circulating insulin in the OVX group. Thus, the receptor:hormone ratio indicated reduced insulin signaling in the DVC and PVN of OVX rats. Leptin receptors were unchanged in the DVC and ARC, but increased over time in the PVN of the Sham group. These changes were accompanied by elevated circulating leptin in both groups that was more pronounced in the OVX group. Thus, the receptor:hormone ratio indicated reduced leptin signaling in the DVC and PVN of both groups, but only in the OVX group for the ARC. Together, these data suggest that weight gain that occurs after removal of ovarian hormones by ovariectomy is associated with selective changes in metabolic hormone signaling in the CNS. While these changes may reflect behavioral or physiological alterations, it remains to be determined whether they cause post-ovariectomy weight gain or result from it.

Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection?

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

Leptin: A Metabolic Signal for the Differentiation of Pituitary Cells

Pituitary cell function is impacted by metabolic states and therefore must receive signals that inform them about nutritional status or adiposity. A primary signal from adipocytes is leptin, which recent studies have shown regulates most pituitary cell types. Subsets of all pituitary cell types express leptin receptors and leptin has been shown to exert transcriptional control through classical JAK/STAT pathways. Recent studies show that leptin also signals through post-transcriptional pathways that involve the translational regulatory protein Musashi. Mechanistically, post-transcriptional control would permit rapid cellular regulation of critical pre-existing pituitary transcripts as energy states change. The chapter will review evidence for transcriptional and/or post-transcriptional regulation of leptin targets (including Gnrhr, activin, Fshb, Gh, Ghrhr, and Pou11f1) and the consequences of the loss of leptin signaling to gonadotrope and somatotrope functions.

Leptin and leptin receptor evaluation in atherosclerotic plaques in patients with type 2 diabetes mellitus

Background. Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction. Aim. Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes. Materials and methods. We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared. Results. No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively). Conclusion. Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy

The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2-/-, model of CGL) and their wild-type control (gBscl2+/+), as well as in mice with selective deficiency in endothelial leptin receptor (LepREC-/-). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL.

Serum levels of inflammatory biomarkers, glycaemic control indices and leptin receptors expression in adult male Wistar rats exposed to oyrethroids

BACKGROUND: Due to widespread use of pesticides, an individual’s lifetime exposure to pesticide mixtures is unavoidable, resulting in potentiation of toxic effects such as changing metabolic signaling temporarily or permanently due to the formation of free radicals among exposed individuals. OBJECTIVE: This study then looked at the expression of leptin and insulin receptors in Wistar rats exposed to pyrethroid and its effects on adipokines and glycemic indices. METHODS: 84 Wistar rats were randomly selected and divided into two groups. 51 rats were exposed to 1.2 % w/v pyrethroid insecticides, while the remaining 33 rats were grouped as non-exposed. The groups were divided into three different groups, each with 7, 21, and 41 days. The animals were anesthetically sacrificed and samples of blood were collected after days of exposure. The levels of total antioxidant status (TAS), malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), nitric oxide (NO), glucose and lipids were determined. Blood activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were also determined. ELISA was used to assess leptin, adiponectin, insulin, CRP, IL-6, and TNFα. Glycaemic indices were calculated appropriately. Leptin and Insulin expression was determined using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Data obtained were statistically compared, and P≤0.05 was considered significant. RESULTS: The mean TChol, TAG, and HDL-C were significantly different (p < 0.05) among the exposed groups. The serum mean levels of SOD, GPx, CAT, GSH, TAS, QUICKI, TNFα, IL6, and CRP were significantly reduced (p < 0.05), while mean levels of MDA, H2O2, NO, insulin, HOMA-IR, FIRI, leptin, and adiponectin were significantly elevated (p < 0.05) in exposed groups. The relative expression of insulin and leptin genes in exposed and non-exposed groups was also shown by column. CONCLUSION: It is self-evident that pyrethroid chemicals exposure may disrupt carbohydrate and lipid metabolism by raising the risk of obesity among the exposed groups.

The Important Role of Leptin in Modulating the Risk of Dermatological Diseases

It is an indisputable fact that obesity is associated with a series of health problems. One important hallmark of obesity is excessive accumulation of lipids in the adipocyte, especially triglyceride (TG). Currently, the adipocyte has been considered not only as a huge repository of excess energy in the form of fat but also as an important source of multiple hormones and cytokines called adipokines. In obesity, the adipocyte is dysfunctional with excessive production and secretion of pro-inflammatory adipokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and leptin. On the other hand, accumulating evidence has shown that leptin plays a vital role in stimulating angiogenesis, controlling lipid metabolism, and modulating the production of pro-inflammatory cytokines. Furthermore, the various activities of leptin are related to the wide distribution of leptin receptors. Notably, it has been reported that enhanced leptin levels and dysfunction of the leptin signaling pathway can influence diverse skin diseases. Recently, several studies revealed the roles of leptin in wound healing, the hair cycle, and the pathogenic development of skin diseases, such as psoriasis, lupus erythematosus, and dermatological cancers. However, the exact mechanisms of leptin in modulating the dermatological diseases are still under investigation. Therefore, in the present review, we summarized the regulatory roles of leptin in the pathological progression of diverse diseases of skin and skin appendages. Furthermore, we also provided evidence to elucidate the complicated relationship between leptin and different dermatological diseases, such as systemic lupus erythematosus (SLE), psoriasis, hidradenitis suppurativa, and some skin tumors.