At The Cutting EdgeImmunomodulatory actions of leptin
Section snippets
Metabolic effects of leptin
Leptin, the product of the gene obese (ob), is a cytokine-like 16-kDa peptide produced by adipose tissue proportionally to the body fat mass (Campfield et al., 1995, Halaas et al., 1995, Zhang et al., 1994). The genetic defect in the leptin (ob) gene in mice results in overeating and reduced energy expenditure, leading to obesity, illustrating the important effects of leptin on maintaining energy balance (Coleman, 1978). Most, if not all, effects of leptin are mediated through the long form of
Evidence in vivo
Several in vivo studies have suggested a potential role for leptin in modulating the immune response (Table 1) (Fantuzzi and Faggioni, 2000). In human and rodents, nutritional deprivation affects both immune function (Chandra, 1991) and circulating leptin levels (Ahima et al., 1996, Grinspoon et al., 1996). Lymphoid atrophy is one of the consequences of prolonged fasting and since leptin levels are drastically reduced under such conditions, it was hypothesized that this adipocyte-derived factor
The immuno-metabolic signaling network
During the last few years it has become evident that leptin participates in functions other than the control of body weight and energy expenditure. A relation has emerged between leptin and inflammation, as evidenced by the altered immune response in genetically obese and starved rodents, as well as the available data on its effect on cytokines and hematopoiesis.
The marked upregulation of IL-1Ra by leptin is of particular interest, since it antagonize IL-1β, which was shown to mediate in part
References (63)
- et al.
A role for leptin and its cognate receptor in hematopoiesis
Curr. Biol.
(1996) Cell-mediated immunity in genetically obese C57BL/6J ob/ob) mice
Am. J. Clin. Nutr.
(1980)1990 McCollum Award lecture. Nutrition and immunity: lessons from the past and new insights into the future
Am. J. Clin. Nutr.
(1991)- et al.
Blood-borne interleukin-1 receptor antagonist crosses the blood–brain barrier
J. Neuroimmunol.
(1994) - et al.
Human leptin stimulates proliferation and activation of human circulating monocytes
Cell. Immunol.
(1999) - et al.
Identification and expression cloning of a leptin receptor OB-R
Cell
(1995) - et al.
Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells
Blood
(1997) - et al.
Role of leptin in the neuroendocrine response to fasting
Nature
(1996) - et al.
Interleukin-1 receptor antagonist: role in biology
Annu. Rev. Immunol.
(1998) - et al.
The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors
Proc. Natl. Acad. Sci. USA
(1996)
Effect of leptin on arterial thrombosis following vascular injury in mice
J. Am. Med. Assoc.
Leptin signaling deficency impairs humoral and cellular immune responses and attenuates experimental arthritis
J. Immunol.
Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks
Science
Selective deletion of leptin receptor in neurons leads to obesity
J. Clin. Invest.
Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice
Diabetologia
Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction
J. Biol. Chem.
Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
J. Clin. Invest.
Leptin deficiency enhances sensitivity to endotoxin-induced lethality
Am. J. Physiol.
LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice
Am. J. Physiol.
Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18
Proc. Natl. Acad. Sci. USA
Leptin in the regulation of immunity, inflammation, and hematopoiesis
J. Leukoc. Biol.
Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays
J. Clin. Invest.
Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity
J. Clin. Invest.
Effect of adrenalectomy and glucocorticoid replacement on development of obesity
Am. J. Physiol.
Leptin directly induces the secretion of Interleukin 1 receptor antagonist in human monocytes
J. Clin. Endocrinol. Metab.
Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein
J. Clin. Invest.
Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells
Proc. Natl. Acad. Sci. USA
Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor
J. Biol. Chem.
Serum leptin levels in women with anorexia nervosa
J. Clin. Endocrinol. Metab.
Weight-reducing effects of the plasma protein encoded by the obese gene
Science
Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor
J. Biol. Chem.
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Visfatin alters the cytokine and matrix-degrading enzyme profile during osteogenic and adipogenic MSC differentiation
2018, Osteoarthritis and CartilageCitation Excerpt :Peripherally, leptin exerts anabolic bone properties by promoting osteoblast differentiation and activity as well as inhibition of osteoclastogenesis, while catabolic effects of leptin are mediated through the central nervous system14. Immunomodulatory effects of leptin have also been described15 and may additionally affect bone turnover via indirect mechanisms. Visfatin, also called nicotinamide phosphoribosyltransferase (Nampt) or pre-B-cell colony enhancing factor (PBEF), is preferentially produced by visceral adipose tissue.
Can prebiotics assist in the management of cognition and weight gain in schizophrenia?
2018, PsychoneuroendocrinologyBiological characteristics of the adipose tissue: adipocyte as an endocrine cell
2012, Revista Medica Clinica Las CondesPsoriasis and systemic inflammatory diseases: Potential mechanistic links between skin disease and co-morbid conditions
2010, Journal of Investigative DermatologyCitation Excerpt :However, leptin is a key factor in regulating a wide range of biological responses, including energy homeostasis, hematopoiesis, neuroendocrine function, and immune responses (Auwerx and Staels, 1998; Fruhbeck et al., 1998; Huang and Li, 2000; Otero et al., 2005). Thus, in addition to being a hypothalamus modulator of food intake, body weight, and fat stores, leptin exerts an important role in acute and chronic inflammatory processes through regulation of cytokine expression that modulates the balance of helper T-cell types 1 and 2 (Juge-Aubry and Meier, 2002; Matarese et al., 2005; Otero et al., 2006). Its receptor is expressed in various tissues, including adipocytes, peripheral blood mononuclear cells, endothelial cell fibroblasts, and injured KCs (Tartaglia, 1997; Eckel et al., 2005).
Behavioral recovery from acute hypoxia is reliant on leptin
2009, Brain, Behavior, and ImmunityCitation Excerpt :How leptin serves as a neuroprotectant is not defined. Leptin is produced by adipose tissue in proportion to body mass (Juge-Aubry and Meier, 2002) and is best known for its role in regulating satiety and energy stores. The effects of leptin are mediated through the leptin receptor, a member of the class I cytokine receptors, similar in structure to the IL-6 receptor (Fruhbeck, 2006).
IL-1 family in breast cancer: Potential interplay with leptin and other adipocytokines
2009, FEBS LettersCitation Excerpt :As it is recognized that leptin acts both at the central nervous system and at the peripheral level, it may also exert its effects in morbid obesity through the IL-1 pathway and IL-1ra may contribute to central leptin resistance by inhibiting the leptin-induced reduction in food intake [75].