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International Journal of Molecular... Jun 2021Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways.... (Review)
Review
Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.
Topics: Animals; Biomarkers; Body Temperature Regulation; Disease Management; Disease Susceptibility; Energy Metabolism; Humans; Hypothalamus; Leptin; Obesity; Signal Transduction; Thermogenesis; Treatment Outcome
PubMed: 34208585
DOI: 10.3390/ijms22126445 -
International Journal of Clinical and... 2011Leptin is a multifunctional adipose-derived cytokines that play a critical role in bodyweight homeostasis and energy balance. Recently, leptin and leptin receptor... (Review)
Review
Leptin is a multifunctional adipose-derived cytokines that play a critical role in bodyweight homeostasis and energy balance. Recently, leptin and leptin receptor dysreulation have been reported in variety of malignant cells including thyroid. Leptin modulates growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3-kinase/AKT and/or Map kinases. In this review, current understanding of leptin's role in the pathogenesis of thyroid cancer has been described.
Topics: Humans; Leptin; Receptors, Leptin; Signal Transduction; Thyroid Neoplasms
PubMed: 22076163
DOI: No ID Found -
Frontiers in Neuroendocrinology Jul 2010Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology... (Review)
Review
Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.
Topics: Energy Metabolism; Homeostasis; Humans; Immune System; Leptin; Metabolic Diseases; Models, Biological; Neurosecretory Systems; Obesity; Reproduction; Signal Transduction
PubMed: 20600241
DOI: 10.1016/j.yfrne.2010.06.002 -
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 -
Neural Plasticity 2016Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism.... (Review)
Review
Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.
Topics: Amenorrhea; Animals; Brain; Female; Hormone Replacement Therapy; Humans; Hypothalamus; Leptin; Lipodystrophy; Male; Mutation; Neuronal Plasticity; Treatment Outcome
PubMed: 26881138
DOI: 10.1155/2016/8528934 -
International Journal of Molecular... May 2016In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous...
In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model.
Topics: Animals; Brain; Eating; Feeding Behavior; Fish Proteins; Gene Expression Regulation; Goldfish; Leptin; Neuropeptide Y; Receptors, Leptin; Recombinant Proteins
PubMed: 27249000
DOI: 10.3390/ijms17060783 -
Journal of Clinical Pathology Jan 2001A major advance in the understanding of the control of appetite, food intake, and energy expenditure came with the discovery of leptin. Leptin concentrations correlate... (Review)
Review
A major advance in the understanding of the control of appetite, food intake, and energy expenditure came with the discovery of leptin. Leptin concentrations correlate with adipose tissue mass, and leptin acts via the central nervous system (CNS) to reduce food intake and increase energy expenditure. A variety of different neurotransmitters have been implicated in mediating the CNS effects of leptin. In humans, leptin deficiency is unlikely to be a major cause of obesity. Most humans are not leptin deficient, but have a leptin concentration raised in proportion to their fat mass. A recent clinical trial looking at the use of recombinant leptin in treating human obesity has resulted in only variable amounts of weight loss. The role of leptin extends beyond the control of food intake and energy expenditure. Leptin reverses many of the physiological responses to starvation. It is suggested that the main role of leptin might be in response to food deprivation and not in obesity.
Topics: Animals; Carrier Proteins; Humans; Leptin; Mice; Obesity; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins; Starvation
PubMed: 11271782
DOI: 10.1136/jcp.54.1.1 -
American Journal of Physiology.... Oct 2011Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy... (Review)
Review
Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics.
Topics: Adipose Tissue; Amenorrhea; Energy Metabolism; Female; Homeostasis; Humans; Hypothalamic Diseases; Hypothalamus; Leptin; Male; Neurosecretory Systems; Reproduction
PubMed: 21791620
DOI: 10.1152/ajpendo.00315.2011 -
Medicine Apr 2021Infections and sepsis are common causes of morbidity and mortality, with an increasing incidence worldwide. Leptin is involved in the inflammatory process and may... (Review)
Review
BACKGROUND
Infections and sepsis are common causes of morbidity and mortality, with an increasing incidence worldwide. Leptin is involved in the inflammatory process and may modulate the cytokine production, immune cell proliferation and endothelial function. There are conflicting results regarding alterations of leptin levels in infectious diseases and the outcome from sepsis.The aim of the current article is to provide an overview of the medical literature on the correlations between variations of leptin levels and infectious diseases and sepsis.
METHODS
We performed an extensive literature search in PubMed and Google Scholar databases, using keywords to identify articles related to leptin in infectious diseases and sepsis. Searches were referenced using medical subject headings that included "leptin," "adipokines," "sepsis," "infectious diseases," "leptin deficiency," "leptin resistance" or "hyperleptinemia." The language of publication, journal, or country were not included as limitation criteria.Articles or abstracts containing adequate information, such as age, sex, anthropometric indices, clinical presentation, comorbidities, and management were included in the study, whereas articles with insufficient clinical and demographic data were excluded. We assessed the quality of the studies selected.The final review of all databases was conducted on June 18, 2020.
RESULTS
We find the results from the current review to be of great importance due to the possible therapeutic role of leptin analogs in states of leptin deficiency associated with infectious diseases or sepsis.In hyperleptinemia, a therapeutic plan for obtaining leptin neutralization also needs further investigations. This could lead to the reduction of proinflammatory responses.There is a need for further studies to demonstrate the specificity and sensitivity of leptin in the early diagnosis of sepsis and the need to measure serum leptin levels in routine evaluation of the critical patient.
CONCLUSION
The multiple effects of leptin are of growing interest, but further studies are needed to elucidate the role of leptin signalling in infectious diseases and sepsis. Because very few human studies are reported, we recommend the need for further research.Better understanding of the pathophysiology of sepsis and the implication of circulating total leptin in this process could help physicians in managing this life-threatening condition.
Topics: Communicable Diseases; Drug Discovery; Early Diagnosis; Humans; Leptin; Prognosis; Sepsis
PubMed: 33907162
DOI: 10.1097/MD.0000000000025720