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PloS One 2022The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on...
The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. Conversely, residues predicted essential for Lep-Lepr interaction displayed divergence between teleosts and tetrapods. Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. Leptin system of Anabantiformes was phylogenetically closer to that of Pleuronectiformes, Scombriformes and Perciformes. Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts.
Topics: Animals; Disulfides; Flatfishes; Leptin; Ligands; Receptors, Leptin
PubMed: 35797380
DOI: 10.1371/journal.pone.0270881 -
Frontiers in Endocrinology 2023Organismal energy balance is controlled by inter-tissue communication mediated by the nervous system and hormones, the disruption of which causes metabolic syndrome... (Review)
Review
Organismal energy balance is controlled by inter-tissue communication mediated by the nervous system and hormones, the disruption of which causes metabolic syndrome exemplified by diabetes and obesity. Fat-storing adipose tissue, especially those located in subcutaneous white adipose tissue, secretes leptin in a proportion of fat mass, inhibiting the accumulation of organismal fat by suppressing appetite and promoting energy expenditure. With a prevalence of obesity that exhibits hyperleptinemia, most of the investigation on leptin has been focused on how it works and how it does not, which is expected to be a clue for treating obesity. In contrast, how it is synthesized, transported, and excreted, all of which are relevant to the homeostasis of blood leptin concentration, are not much understood. Of note, acute leptin reduction after hyperleptinemia in the context of obesity exhibited a beneficial effect on obesity and insulin sensitivity, indicating that manipulation of circulating leptin level may provide a therapeutic strategy. Technological advances such as "omics" analysis combined with sophisticated gene-engineered mice studies in the past decade enabled a deeper understanding of leptin's action in more detail. Here, we summarize the updated understanding of the action as well as regulation of leptin and point out the emerging direction of research on leptin.
Topics: Mice; Animals; Leptin; Adipokines; Adipose Tissue; Obesity; Diabetes Mellitus
PubMed: 37547309
DOI: 10.3389/fendo.2023.1172060 -
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 -
Cell Death & Disease Oct 2018Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies... (Review)
Review
Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies have identified an underlying role for leptin in regulation of mood and cognition via regulation of synaptic changes in the brain that have been associated with antidepressant-like actions. Brain neural plasticity occurs in response to a range of intrinsic and extrinsic stimuli, including those that may mediate the effects of antidepressants. Neural plasticity theories of depression are thought to explain multiple aspects of depression and the effects of antidepressants. It is also well documented that leptin has effects on neural plasticity. This review summarizes the recent literature on the role of leptin in neural plasticity in order to elaborate the possible mechanism of leptin's antidepressant-like effects. Recent findings provide new insights into the underlying mechanisms of neural plasticity in depression. Leptin may influence these mechanisms and consequently constitute a possible target for novel therapeutic approaches to the treatment of depression.
Topics: Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Depression; Disease Models, Animal; Female; Hippocampus; Humans; Hypothalamus; Leptin; Long-Term Potentiation; Long-Term Synaptic Depression; Male; Mice; Molecular Targeted Therapy; Neurogenesis; Rats
PubMed: 30367065
DOI: 10.1038/s41419-018-1129-1 -
Journal of Chemical Neuroanatomy Nov 2014Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been... (Review)
Review
Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as anti-psychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including autism spectrum disorders and Rhett disorder. Further, studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations.
Topics: Animals; Brain; Female; Humans; Leptin; Mental Disorders; Obesity; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 24862904
DOI: 10.1016/j.jchemneu.2014.05.001 -
The Journal of Endocrinology Oct 2014The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in... (Review)
Review
The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways.
Topics: Animals; Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Leptin; Models, Biological; Neurons; Reproduction; Sexual Maturation
PubMed: 25118207
DOI: 10.1530/JOE-14-0413 -
The Journal of Veterinary Medical... Apr 2020This study aims to investigate and compare the expressions of leptin and ghrelin in the gastrointestinal tracts of calves and cows. The mRNA expression of leptin in the...
This study aims to investigate and compare the expressions of leptin and ghrelin in the gastrointestinal tracts of calves and cows. The mRNA expression of leptin in the rumen, abomasum, and jejunum of calves was significantly higher than that in cows. In both calves and cows, abomasum ghrelin mRNA expression was significantly higher than that in other gastrointestinal tracts. In calves, leptin protein expression in the abomasum was the highest. In addition, leptin protein expression in the abomasum and jejunum of calves was significantly higher than that in cows. Results indicated that leptin in the abomasum and jejunum plays an important role during the suckling period in a ruminant.
Topics: Animals; Cattle; Female; Gastrointestinal Tract; Gene Expression; Ghrelin; Leptin; Male; RNA, Messenger
PubMed: 32092743
DOI: 10.1292/jvms.19-0680 -
Lipids in Health and Disease Feb 2020Antipsychotic-induced weight gain is the most prevalent somatic adverse event occurring in patients treated by antipsychotics, especially atypical antipsychotics. It is... (Review)
Review
Antipsychotic-induced weight gain is the most prevalent somatic adverse event occurring in patients treated by antipsychotics, especially atypical antipsychotics. It is of particular interest because of its repercussion on cardiovascular morbidity and mortality especially now that the use of second-generation antipsychotics has been extended to other mental health illnesses such as bipolar disorders and major depressive disorder. The mechanism underlying antipsychotics-induced weight gain is still poorly understood despite a significant amount of work on the topic. Recently, there has been an on-going debate of tremendous research interest on the relationship between antipsychotic-induced weight gain and body weight regulatory hormones such as leptin. Given that, researchers have brought to light the question of leptin's role in antipsychotic-induced weight gain. Here we summarize and discuss the existing evidence on the link between leptin and weight gain related to antipsychotic drugs, especially atypical antipsychotics.
Topics: Antipsychotic Agents; Depressive Disorder, Major; Female; Humans; Leptin; Male; Weight Gain
PubMed: 32033608
DOI: 10.1186/s12944-020-01203-z -
Vascular Health and Risk Management 2006Leptin, a peptide discovered more than 10 years ago, decreases food intake and increases sympathetic nerve activity to both thermogenic and non-thermogenic tissue.... (Review)
Review
Leptin, a peptide discovered more than 10 years ago, decreases food intake and increases sympathetic nerve activity to both thermogenic and non-thermogenic tissue. Leptin was initially believed to be an anti-obesity hormone, owing to its metabolic effects. However, obese individuals, for unknown reasons, become resistant to the satiety and weight-reducing effect of the hormone, but preserve leptin-mediated sympathetic activation to non-thermogenic tissue such as kidney, heart, and adrenal glands. Leptin has been shown to influence nitric oxide production and natriuresis, and along with chronic sympathetic activation, especially to the kidney, it may lead to sodium retention, systemic vasoconstriction, and blood pressure elevation. Consequently, leptin is currently considered to play an important role in the development of hypertension in obesity.
Topics: Abdominal Fat; Animals; Antihypertensive Agents; Appetite Regulation; Blood Pressure; Body Weight; Energy Metabolism; Humans; Hypertension; Kidney; Leptin; Nitric Oxide; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Time Factors
PubMed: 17319461
DOI: 10.2147/vhrm.2006.2.2.163 -
Endocrine Reviews Jun 2013Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions.... (Review)
Review
Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
Topics: Animals; Diabetes Mellitus; HIV-Associated Lipodystrophy Syndrome; Humans; Hypoglycemic Agents; Insulin Resistance; Leptin; Lipodystrophy, Congenital Generalized; Receptors, Leptin; Signal Transduction
PubMed: 23475416
DOI: 10.1210/er.2012-1053