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International Journal of Molecular... May 2019Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an... (Review)
Review
Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an adipokine regulating body fat mass, represents a key molecule in obesity, able to modulate immune responses and foster chronic inflammatory response in peripheral tissues. High levels of cytokines and inflammatory markers suggest an association between inflammatory state and obesity in dogs, highlighting the parallelism with humans. Canine obesity is a relevant disease always accompanied with several health conditions such as inflammation, immune-dysregulation, insulin resistance, pancreatitis, orthopaedic disorders, cardiovascular disease, and neoplasia. However, leptin involvement in many disease processes in veterinary medicine is poorly understood. Moreover, hyperleptinemia as well as leptin resistance occur with cardiac dysfunction as a consequence of altered cardiac mitochondrial metabolism in obese dogs. Similarly, leptin dysregulation seems to be involved in the pancreatitis pathophysiology. This review aims to examine literature concerning leptin and immunological status in obese dogs, in particular for the aspects related to obesity-associated diseases.
Topics: Adaptive Immunity; Animals; Dog Diseases; Dogs; Immunity, Innate; Leptin; Obesity
PubMed: 31091785
DOI: 10.3390/ijms20102392 -
Current Opinion in Endocrinology,... Oct 2015To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which... (Review)
Review
PURPOSE OF REVIEW
To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity.
RECENT FINDINGS
The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to possibly treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin tolerance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but could possibly be useful in combination with other therapies or for weight loss maintenance.
SUMMARY
Leptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, whereas the development of new techniques and drug combinations which may improve leptin's efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity.
Topics: Animals; Humans; Leptin; Lipodystrophy; Obesity
PubMed: 26313897
DOI: 10.1097/MED.0000000000000184 -
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 -
Molecular Metabolism Sep 2017The hormone leptin is an important regulator of metabolic homeostasis, able to inhibit food intake and increase energy expenditure. Leptin can also independently lower... (Review)
Review
BACKGROUND
The hormone leptin is an important regulator of metabolic homeostasis, able to inhibit food intake and increase energy expenditure. Leptin can also independently lower blood glucose levels, particularly in hyperglycemic models of leptin or insulin deficiency. Despite significant efforts and relevance to diabetes, the mechanisms by which leptin acts to regulate blood glucose levels are not fully understood.
SCOPE OF REVIEW
Here we assess literature relevant to the glucose lowering effects of leptin. Leptin receptors are widely expressed in multiple cell types, and we describe both peripheral and central effects of leptin that may be involved in lowering blood glucose. In addition, we summarize the potential clinical application of leptin in regulating glucose homeostasis.
MAJOR CONCLUSIONS
Leptin exerts a plethora of metabolic effects on various tissues including suppressing production of glucagon and corticosterone, increasing glucose uptake, and inhibiting hepatic glucose output. A more in-depth understanding of the mechanisms of the glucose-lowering actions of leptin may reveal new strategies to treat metabolic disorders.
Topics: Animals; Blood Glucose; Corticosterone; Diabetes Mellitus; Eating; Energy Metabolism; Glucagon; Glucose; Homeostasis; Humans; Insulin; Insulin Secretion; Leptin; Liver; Receptors, Leptin
PubMed: 28951828
DOI: 10.1016/j.molmet.2017.04.011 -
Cellular and Molecular Life Sciences :... Mar 2013Leptin is an adipocyte-derived hormone involved in a myriad of physiological process, including the control of energy balance and several neuroendocrine axes.... (Review)
Review
Leptin is an adipocyte-derived hormone involved in a myriad of physiological process, including the control of energy balance and several neuroendocrine axes. Leptin-deficient mice and humans are obese, diabetic, and display a series of neuroendocrine and autonomic abnormalities. These individuals are infertile due to a lack of appropriate pubertal development and inadequate synthesis and secretion of gonadotropins and gonadal steroids. Leptin receptors are expressed in many organs and tissues, including those related to the control of reproductive physiology (e.g., the hypothalamus, pituitary gland, and gonads). In the last decade, it has become clear that leptin receptors located in the brain are major players in most leptin actions, including reproduction. Moreover, the recent development of molecular techniques for brain mapping and the use of genetically modified mouse models have generated crucial new findings for understanding leptin physiology and the metabolic influences on reproductive health. In the present review, we will highlight the new advances in the field, discuss the apparent contradictions, and underline the relevance of this complex physiological system to human health. We will focus our review on the hypothalamic circuitry and potential signaling pathways relevant to leptin's effects in reproductive control, which have been identified with the use of cutting-edge technologies of molecular mapping and conditional knockouts.
Topics: Animals; Energy Metabolism; Female; Fertility; Gonads; Humans; Hypothalamus; Leptin; Male; Pituitary Gland; Puberty; Reproduction; Signal Transduction
PubMed: 22851226
DOI: 10.1007/s00018-012-1095-1 -
Biochimie Oct 2012Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine... (Review)
Review
Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority of the evidence among children however suggests that systemic leptin may be associated with greater asthma prevalence and severity, particularly among prepubertal boys and peripubertal/postpubertal girls. Systemic and airway leptin concentrations may also be disproportionately higher in chronic obstructive pulmonary disease (COPD) patients, particularly among women, and reflect greater airway inflammation and disease severity. Quite like leptin, the association between systemic and airway adiponectin and asthma in humans is also controversial. Some but not all studies, demonstrate that serum adiponectin concentrations are protective against asthma among premenopausal women and peripubertal girls. On the other hand, serum adiponectin concentrations are inversely associated with asthma severity among boys but positively associated among men. Further, systemic and airway adiponectin concentrations are higher in COPD patients than controls, as demonstrated by case-control studies of men. Systemic adiponectin is also positively associated with lung function in healthy adults but inversely associated with lung function in subjects with COPD. It is therefore possible that pro-inflammatory effects of adiponectin dominate under certain physiologic conditions and anti-inflammatory effects under others. The adipokine-lung disease literature has critical gaps that include a lack of adequately powered longitudinal or weight-intervention studies; inadequate adjustment for confounding effect of obesity; and unclear understanding of potential sex interactions. It is also uncertain whether adipokine derangements precede pulmonary disease or are a consequence of it. Future research will determine whether modulation of adipokines, independent of BMI, may allow novel ways to prevent or treat inflammatory pulmonary conditions.
Topics: Adiponectin; Animals; Humans; Leptin; Lung Diseases
PubMed: 22445899
DOI: 10.1016/j.biochi.2012.03.006 -
Drug News & Perspectives Sep 2005Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging... (Review)
Review
Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity-related CVD. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. These recent discoveries could lead to novel strategies for treatment of obesity-associated CVD.
Topics: Adult; Animals; Cardiovascular Diseases; Endothelin-1; Humans; Leptin; Obesity; Reactive Oxygen Species; Sympathetic Nervous System; Ventricular Remodeling
PubMed: 16362081
DOI: 10.1358/dnp.2005.18.7.939346 -
Cytokine & Growth Factor Reviews Dec 2017The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals,... (Review)
Review
The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin's association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin's potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.
Topics: Animals; Cell Movement; Humans; Leptin; Neoplasm Metastasis; Neoplasms; Obesity; Signal Transduction
PubMed: 29158066
DOI: 10.1016/j.cytogfr.2017.11.002 -
Reproduction (Cambridge, England) Jan 2018Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such... (Review)
Review
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells. The leptin expression is induced involving the cAMP/PKA or cAMP/Epac pathways which have profound actions upon human trophoblast function. The activation of PI3K and MAPK pathways also participates in the leptin expression. Estrogens play a central role during pregnancy, particularly 17β-estradiol upregulates the leptin expression in placental cells through genomic and non-genomic actions. The leptin promoter analysis reveals specific elements that are active in placental cells. The transcription factors CREB, AP1, Sp1, NFκB and the coactivator CBP are involved in the placental leptin expression. Moreover, placental leptin promoter is a target of epigenetic marks such as DNA methylation and histone acetylation that regulates not only the leptin expression in placenta during pregnancy but also determines the predisposition of acquiring adult metabolism diseases. Taken together, all these results allow a better understanding of leptin function and regulatory mechanisms of leptin expression in human placental trophoblasts, and support the importance of leptin during pregnancy and in programming adult health.
Topics: Animals; Female; Humans; Leptin; Placenta; Pregnancy; Signal Transduction
PubMed: 29018059
DOI: 10.1530/REP-17-0512 -
International Journal of Molecular... Aug 2020Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of... (Review)
Review
Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity.
Topics: Adaptive Immunity; Animals; Autoimmune Diseases; Communicable Diseases; Humans; Immunity, Innate; Leptin; Obesity
PubMed: 32824322
DOI: 10.3390/ijms21165887