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Frontiers in Endocrinology 2021Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic... (Review)
Review
Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed.
Topics: Adipocytes; Adipose Tissue; Aging, Premature; Humans; Inflammation; Insulin Resistance; Leptin; Lipodystrophy; Lipomatosis; Syndrome
PubMed: 35046902
DOI: 10.3389/fendo.2021.803189 -
Annales de Biologie Clinique Jun 2020The identification of leptin allowed the discovery of a new endocrine system. This major adipokine controlling energy homeostasis is also involved in the regulation of... (Review)
Review
The identification of leptin allowed the discovery of a new endocrine system. This major adipokine controlling energy homeostasis is also involved in the regulation of neuroendocrine function and fertility. Unfortunately, leptin is not able to treat common obesity, which associates hyperleptinemia and resistance to the hormone. Conversely, treatment with recombinant leptin is effective in situations of leptin deficiency. Several pathophysiological situations associated with adipose tissue dysfunctions and abnormal regulation of leptin secretion are discussed in this review. The advantage of the potential use of the leptin assay in some pathophysiological conditions is proposed.
Topics: Adipokines; Adipose Tissue; Animals; Homeostasis; Humans; Leptin; Obesity; Secretory Pathway
PubMed: 32540812
DOI: 10.1684/abc.2020.1560 -
International Journal of Molecular... Apr 2021Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic... (Review)
Review
Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.
Topics: Animals; Female; Fetal Growth Retardation; Humans; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Leptin
PubMed: 33925454
DOI: 10.3390/ijms22094569 -
International Journal of Molecular... Mar 2022White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a... (Review)
Review
White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a plethora of hormones and cytokines namely adipokines. Discovered in 1994, leptin has emerged as a key molecule with pleiotropic functions. It is primarily recognized for its role in regulating energy homeostasis and food intake. Currently, further evidence suggests its potent role in reproduction, glucose metabolism, hematopoiesis, and interaction with the immune system. It is implicated in both innate and adaptive immunity, and it is reported to contribute, with other adipokines, in the cross-talking networks involved in the pathogenesis of chronic inflammation and immune-related diseases of the musculo-skeletal system such as osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the most recent findings concerning the involvement of leptin in immunity and inflammatory responses in OA and RA.
Topics: Adipokines; Arthritis, Rheumatoid; Humans; Immune System Diseases; Inflammation; Leptin; Osteoarthritis
PubMed: 35270000
DOI: 10.3390/ijms23052859 -
Journal of Neurochemistry May 2023The discovery of leptin in 1994 was an "eureka moment" in the field of neurometabolism that provided new opportunities to better understand the central control of energy... (Review)
Review
The discovery of leptin in 1994 was an "eureka moment" in the field of neurometabolism that provided new opportunities to better understand the central control of energy balance and glucose metabolism. Rapidly, a prevalent model in the field emerged that pro-opiomelanocortin (POMC) neurons were key in promoting leptin's anorexigenic effects and that the arcuate nucleus of the hypothalamus (ARC) was a key region for the regulation of energy homeostasis. While this model inspired many important discoveries, a growing body of literature indicates that this model is now outdated. In this review, we re-evaluate the hypothalamic leptin-melanocortin model in light of recent advances that directly tackle previous assumptions, with a particular focus on the ARC. We discuss how segregated and heterogeneous these neurons are, and examine how the development of modern approaches allowing spatiotemporal, intersectional, and chemogenetic manipulations of melanocortin neurons has allowed a better definition of the complexity of the leptin-melanocortin system. We review the importance of leptin in regulating glucose homeostasis, but not food intake, through direct actions on ARC POMC neurons. We further highlight how non-POMC, GABAergic neurons mediate leptin's direct effects on energy balance and influence POMC neurons.
Topics: Leptin; Melanocortins; Pro-Opiomelanocortin; Hypothalamus; Arcuate Nucleus of Hypothalamus; Energy Metabolism
PubMed: 36648204
DOI: 10.1111/jnc.15765 -
Lipids in Health and Disease Oct 2020Leptin is an adipokine, adipocyte-derived compound, which acts both as a hormone and cytokine. It is mainly synthesized by adipocytes of white adipose tissue. Leptin... (Review)
Review
Leptin is an adipokine, adipocyte-derived compound, which acts both as a hormone and cytokine. It is mainly synthesized by adipocytes of white adipose tissue. Leptin possesses pleiotropic functions including, among others, stimulation of angiogenesis and production of proinflammatory cytokines. The various types of leptin activity are related to the wide distribution of leptin receptors. This adipokine acts by activating intracellular signaling cascades such as JAKs (Janus kinases), STATs (signal transducers and activators of transcription), and others.In a course of obesity, an increased serum level of leptin coexists with tissue receptor resistance. It has been reported that enhanced leptin levels, leptin receptor impairment, and dysfunction of leptin signaling can influence skin and hair. The previous studies revealed the role of leptin in wound healing, hair cycle, and pathogenesis of skin diseases like psoriasis, lupus erythematosus, and skin cancers. However, the exact mechanism of leptin's impact on the skin is still under investigation. Herein, we present the current knowledge concerning the role of leptin in psoriasis and selected skin diseases.
Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Humans; Janus Kinases; Leptin; Lupus Erythematosus, Cutaneous; Psoriasis; Receptors, Leptin; STAT Transcription Factors; Signal Transduction; Skin Diseases; Skin Neoplasms
PubMed: 33008429
DOI: 10.1186/s12944-020-01391-8 -
Cells Sep 2022Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin...
Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.
Topics: Animals; Cerebral Hemorrhage; Endothelial Cells; Humans; Leptin; Mice; Neovascularization, Physiologic; Pericytes; STAT3 Transcription Factor
PubMed: 36078162
DOI: 10.3390/cells11172755 -
Stem Cell Reviews and Reports Apr 2021Hematopoietic stem cells (HSCs) give rise to all blood and immune cells in the body. These rare cells reside in the hypoxic niche of the bone marrow (BM) where they are... (Review)
Review
Hematopoietic stem cells (HSCs) give rise to all blood and immune cells in the body. These rare cells reside in the hypoxic niche of the bone marrow (BM) where they are subjected to a complex network of regulatory factors including cellular and molecular components. To sustain hematopoiesis over the lifetime of an individual, HSCs maintain distinctive metabolic programs, and in recent years nutritional factors have been increasingly recognized as critical regulators of HSC numbers and functions. Leptin (LEP), a neuroendocrine messenger, and its receptor (LEPR) are well-known for their immunomodulatory and energy balancing effects; yet, how LEP/LEPR signaling plays a role in hematopoiesis is under-appreciated. In this review, we summarize and highlight recent work that demonstrated involvement of LEP/LEPR in hematopoiesis under steady state or stress-associated situations as well as in pathological conditions such as cardiovascular diseases and malignancies. Although the field is only in its infancy, these studies suggest evidence of potential clinical applications and proof-of-principle for more in-depth future research. Under steady state, only a minor subset of long-term hematopoietic stem cells (HSCs) express LEPR. Upon irradiation, LEPRHSCs exhibited robust repopulating capacity in long-term engraftment studies that outcompeted LEPRHSCs. LEPR stromal cells secrete critical niche factors including stem cell factor (SCF) and pleiotrophin (PTN) to support HSCs and progenitor cells. LEPR signaling mediated protective effects of fasting in ALL but not AML leukemias.
Topics: Hematopoiesis; Hematopoietic Stem Cells; Humans; Leptin; Receptors, Leptin
PubMed: 33598894
DOI: 10.1007/s12015-021-10132-y -
PeerJ 2023Leptin is a peptide hormone that regulates energy balance, immune inflammatory response, and bone metabolism. Several studies have demonstrated a relationship between... (Review)
Review
Leptin is a peptide hormone that regulates energy balance, immune inflammatory response, and bone metabolism. Several studies have demonstrated a relationship between leptin and periodontitis, a local inflammatory disease that progressively weakens the supporting structures of the teeth, eventually leading to tooth loss. This article reviews the existing literature and discusses leptin's basic characteristics, its relationship with periodontitis, and its effects on periodontal tissue metabolism.
Topics: Humans; Leptin; Periodontitis; Signal Transduction; Energy Metabolism
PubMed: 38111655
DOI: 10.7717/peerj.16633 -
International Journal of Molecular... Feb 2022Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a... (Review)
Review
Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses.
Topics: Animals; Cell Differentiation; Dental Pulp; Humans; Leptin; Odontogenesis; Periodontal Ligament
PubMed: 35216099
DOI: 10.3390/ijms23041984