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Zeitschrift Fur Kinder- Und... Jan 2021
Topics: Affect; Anorexia Nervosa; Behavior; Cognition; Humans; Leptin; Time Factors
PubMed: 33423560
DOI: 10.1024/1422-4917/a000775 -
Cytokine Oct 2017After its discovery as a key controller of metabolic function, leptin has been later extensively implicated in additional functions including important modulatory... (Review)
Review
After its discovery as a key controller of metabolic function, leptin has been later extensively implicated in additional functions including important modulatory activities on the innate and adaptive immune response. This review analyzes the known implications of leptin in multiple inflammatory conditions, including autoimmune diseases, and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses.
Topics: Adaptive Immunity; Animals; Autoimmunity; Humans; Immunity, Innate; Inflammation; Leptin; Mice; Obesity
PubMed: 27916613
DOI: 10.1016/j.cyto.2016.10.011 -
Biomolecules Jul 2021Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control... (Review)
Review
Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control different processes, such as the regulation of body weight and energy expenditure, reproductive function, immune response, and bone metabolism. In addition, leptin can exert angiogenic and mitogenic actions in peripheral organs. Leptin biological activities are greatly related to its interaction with the leptin receptor. Both leptin excess and leptin deficiency, as well as leptin resistance, are correlated with different human pathologies, such as autoimmune diseases and cancers, making leptin and leptin receptor important drug targets. The development of leptin signaling modulators represents a promising strategy for the treatment of cancers and other leptin-related diseases. In the present manuscript, we provide an update review about leptin-activity modulators, comprising leptin mutants, peptide-based leptin modulators, as well as leptin and leptin receptor specific monoclonal antibodies and nanobodies.
Topics: Animals; Binding Sites; Humans; Leptin; Peptides; Receptors, Leptin; Single-Domain Antibodies
PubMed: 34356668
DOI: 10.3390/biom11071045 -
Endocrine Reviews Apr 2020Animals that lack the hormone leptin become grossly obese, purportedly for 2 reasons: increased food intake and decreased energy expenditure (thermogenesis). This review... (Review)
Review
Animals that lack the hormone leptin become grossly obese, purportedly for 2 reasons: increased food intake and decreased energy expenditure (thermogenesis). This review examines the experimental evidence for the thermogenesis component. Analysis of the data available led us to conclude that the reports indicating hypometabolism in the leptin-deficient ob/ob mice (as well as in the leptin-receptor-deficient db/db mice and fa/fa rats) derive from a misleading calculation artefact resulting from expression of energy expenditure per gram of body weight and not per intact organism. Correspondingly, the body weight-reducing effects of leptin are not augmented by enhanced thermogenesis. Congruent with this, there is no evidence that the ob/ob mouse demonstrates atrophied brown adipose tissue or diminished levels of total UCP1 mRNA or protein when the ob mutation is studied on the inbred C57BL/6 mouse background, but a reduced sympathetic nerve activity is observed. On the outbred "Aston" mouse background, brown adipose tissue atrophy is seen, but whether this is of quantitative significance for the development of obesity has not been demonstrated. We conclude that leptin is not a thermogenic hormone. Rather, leptin has effects on body temperature regulation, by opposing torpor bouts and by shifting thermoregulatory thresholds. The central pathways behind these effects are largely unexplored.
Topics: Animals; Energy Metabolism; Humans; Leptin; Mice; Obesity; Rats; Thermogenesis
PubMed: 31774114
DOI: 10.1210/endrev/bnz016 -
International Journal of Molecular... Apr 2022Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk... (Review)
Review
Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin's relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.
Topics: Adipokines; Adipose Tissue; Colorectal Neoplasms; Humans; Leptin; Obesity; Receptors, Leptin
PubMed: 35563103
DOI: 10.3390/ijms23094713 -
BMC Genomics Jul 2014A LEP transcript up-regulated in lungs of ducks (Anas platyrhynchos) infected by avian influenza A virus was recently described in the Nature Genetics manuscript that...
BACKGROUND
A LEP transcript up-regulated in lungs of ducks (Anas platyrhynchos) infected by avian influenza A virus was recently described in the Nature Genetics manuscript that reported the duck genome. In vertebrates, LEP gene symbol is reserved for leptin, the key regulator of energy balance in mammals.
RESULTS
Launching an extensive search for this gene in the genome data that was submitted to the public databases along with duck genome manuscript and extending this search to all avian genomes in the whole-genome shotgun-sequencing database, we were able to report the first identification of coding sequences capable of encoding the full leptin protein precursor in wild birds. Gene structure, synteny and sequence-similarity (up to 54% identity and 68% similarity) to reptilian leptin evident in falcons (Falco peregrinus and cherrug), tits (Pseudopodoces humilis), finches (Taeniopygia guttata) and doves (Columba livia) confirmed that the bird leptin was a true ortholog of its mammalian form. Nevertheless, in duck, like other domestic fowls the LEP gene was not identifiable.
CONCLUSION
Lack of the LEP gene in poultry suggests that birds that have lost it are particularly suited to domestication. Identification of an intact avian gene for leptin in wild birds might explain in part the evolutionary conservation of its receptor in leptin-less fowls.
Topics: Amino Acid Sequence; Animals; Avian Proteins; Base Sequence; Ducks; Leptin; Molecular Sequence Data; Sequence Analysis, DNA; Synteny
PubMed: 24992969
DOI: 10.1186/1471-2164-15-551 -
Physiology & Behavior Jul 2017The adipocyte-derived hormone leptin is an important regulator of body weight and metabolism through activation of brain leptin receptors expressed in regions such as... (Review)
Review
The adipocyte-derived hormone leptin is an important regulator of body weight and metabolism through activation of brain leptin receptors expressed in regions such as the hypothalamus. Beyond these well described and characterized activities of leptin in the hypothalamus, it is becoming increasingly clear that the central activities of leptin extend to the hippocampus. Indeed, leptin receptors are expressed in the hippocampus where these receptors are proposed to mediate various aspects of hippocampal synaptic plasticity that ultimately impact cognitive function. This concept is supported by studies demonstrating that leptin promotes hippocampal-dependent learning and memory, as well as studies indicating that leptin resistance is associated with deficits in hippocampal-dependent behaviors and in the induction of depressive-like behaviors. The effects of leptin on cognitive/behavioral plasticity in the hippocampus may be regulated by direct activation of leptin receptors expressed in the hippocampus; additionally, leptin-mediated activation of synaptic networks that project to the hippocampus may also impact hippocampal-mediated behaviors. In view of these previous observations, the goal of this review will be to discuss the mechanisms through which leptin facilitates cognition and behavior, as well as to dissect the loci at which leptin resistance leads to impairments in hippocampal synaptic plasticity, including the development of cognitive deficits and increased risk of depressive illness in metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM).
Topics: Animals; Hippocampus; Humans; Leptin; Mental Disorders; Signal Transduction
PubMed: 28267584
DOI: 10.1016/j.physbeh.2017.03.002 -
Neuroscience Nov 2020Amylin is co-secreted with insulin by pancreatic β-cells in response to a meal and produced by neurons in discrete hypothalamic brain areas. Leptin is proportionally... (Review)
Review
Amylin is co-secreted with insulin by pancreatic β-cells in response to a meal and produced by neurons in discrete hypothalamic brain areas. Leptin is proportionally secreted by the adipose tissue. Both hormones control food intake and energy homeostasis post-weaning in rodents. While amylin's main site of action is located in the area postrema (AP) and leptin's is located in the mediobasal hypothalamus, both hormones can also influence the other's signaling pathway; amylin has been shown enhance hypothalamic leptin signaling, and amylin signaling in the AP may rely on functional leptin receptors to modulate its effects. These two hormones also play major roles during other life periods. During pregnancy, leptin levels rise as a result of an increase in fat depot resulting in gestational leptin-resistance to prepare the maternal body for the metabolic needs during fetal development. The role of amylin is far less studied during pregnancy and lactation, though amylin levels seem to be elevated during pregnancy relative to insulin. Whether amylin and leptin interact during pregnancy and lactation remains to be assessed. Lastly, during brain development, amylin and leptin are major regulators of cell birth during embryogenesis and act as neurotrophic factors in the neonatal period. This review will highlight the role of amylin and leptin, and their possible interaction, during these dynamic time periods of pregnancy, lactation, and early development.
Topics: Amyloid; Child Development; Female; Humans; Infant, Newborn; Islet Amyloid Polypeptide; Lactation; Leptin; Pregnancy; Receptors, Leptin
PubMed: 31846753
DOI: 10.1016/j.neuroscience.2019.11.034 -
Metabolism: Clinical and Experimental Jan 2015Leptin has key roles in the regulation of energy balance, body weight, metabolism, and endocrine function. Leptin levels are undetectable or very low in patients with... (Review)
Review
Leptin has key roles in the regulation of energy balance, body weight, metabolism, and endocrine function. Leptin levels are undetectable or very low in patients with lipodystrophy, hypothalamic amenorrhea, and congenital leptin deficiency (CLD) due to mutations in the leptin gene. For these patients, leptin replacement therapy with metreleptin (a recombinant leptin analog) has improved or normalized most of their phenotypes, including normalization of endocrine axes, decrease in insulin resistance, and improvement of lipid profile and hepatic steatosis. Remarkable weight loss has been observed in patients with CLD. Due to its effects, leptin therapy has also been evaluated in conditions where leptin levels are normal or high, such as common obesity, diabetes (types 1 and 2), and Rabson-Mendenhall syndrome. A better understanding of the physiological roles of leptin may lead to the development of leptin-based therapies for other prevalent disorders such as obesity-associated nonalcoholic fatty liver disease, depression and dementia.
Topics: Animals; Body Weight; Energy Metabolism; Hormone Replacement Therapy; Humans; Leptin
PubMed: 25156686
DOI: 10.1016/j.metabol.2014.07.014 -
Diabetes May 2020The successful use of leptin for the treatment of individuals with lipodystrophy and leptin deficiency is well established. However, pharmacological approaches of leptin...
The successful use of leptin for the treatment of individuals with lipodystrophy and leptin deficiency is well established. However, pharmacological approaches of leptin therapy for the treatment of diet-induced obesity have been ineffective. There is ample room for a better understanding of the much famed "leptin resistance" phenomenon. Our recent data in this area prompt us to call for a conceptual shift. This shift entails a model in which a reduction of bioactive leptin levels in the context of obesity triggers a high degree of leptin sensitization and improved leptin action, both centrally and peripherally. Put another way, hyperleptinemia per se causes leptin resistance and associated metabolic disorders. In this perspective, we briefly discuss the underlying conceptual steps that led us to explore partial leptin reduction as a viable therapeutic avenue. We hope this discussion will contribute to potential future applications of partial leptin reduction therapy for the treatment of obesity and type 2 diabetes.
Topics: Animals; Biological Evolution; Humans; Leptin; Mice; Obesity
PubMed: 32312898
DOI: 10.2337/dbi19-0018