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Current Rheumatology Reports Dec 2019Osteoarthritis (OA) is an aging-associated and injury-induced joint disease characterized by cartilage degradation, bone sclerosis, and persistent low-grade inflammation... (Review)
Review
PURPOSE OF THE REVIEW
Osteoarthritis (OA) is an aging-associated and injury-induced joint disease characterized by cartilage degradation, bone sclerosis, and persistent low-grade inflammation in the joint. Aging and injury are triggers of joint pathological changes mediated by pro-inflammatory factors, some of which are secreted by white adipose tissue. Adipokines including adiponectin, leptin, resistin, chemerin, IL-6, and TNF-α are major players not only during inflammation but also in metabolic regulation of joint cells including chondrocytes, osteoblasts, osteoclasts as well as mesenchymal stem cells. The purpose of this review is to summarize the signal transduction pathways of adipokines in the articular joint to provide new information on potential targets for intervention of OA.
RECENT FINDINGS
The risk of knee osteoarthritis is associated with adipokine gene polymorphism. While the infrapatellar fat pad is a major source of adipokines in knee synovial fluid, adipocytes also accumulate in the bone marrow during aging and obesity. Adipokines can act as SASPs (senescence associated secretory phenotype factors) that participate in cellular senescence of chondrocytes, but they also regulate energy metabolism impacting bone remodeling. Thus, adipokines are closely related to the metabolic syndrome and degenerative pathological changes in cartilage and bone during OA. Modulating the effects of adipokines on different cell types in the intra-articular joint will be a promising new option for OA intervention.
Topics: Adipokines; Humans; Osteoarthritis
PubMed: 31813080
DOI: 10.1007/s11926-019-0868-z -
Reviews in Endocrine & Metabolic... Dec 2021We review the effects of acute and long-term physical activity on adipokine levels in individuals with type 2 diabetes (T2D). Three electronic databases were searched.... (Review)
Review
We review the effects of acute and long-term physical activity on adipokine levels in individuals with type 2 diabetes (T2D). Three electronic databases were searched. Studies made in animal models were excluded, while studies based on participants with and without T2D, and also studies with type 1 diabetes were included. Of the 2,450 citations, 63 trials, including randomised control trials, cross-sectional and longitudinal studies, met our inclusion criteria. Seventy and five percent of studies reported the effects of physical activity on tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6), adiponectin, visfatin, omentin-1, and leptin levels. There are no robust results due to variations in exercise modality, intensity, duration, and also differences in cohort characteristics in the literature. Only four studies described the effects of an acute session of physical activity on adipokine levels. Overall, physical activity improves diabetes status by regulating adipokine levels. However, long-term aerobic + resistance training combined with dietary modifications is likely to be a more effective strategy for improving adipokines profiles in patients with type 2 diabetes.
Topics: Adipokines; Adiponectin; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Exercise; Humans; Leptin
PubMed: 33931803
DOI: 10.1007/s11154-021-09657-x -
Neuroendocrinology 2007The brain has been recognized as a prominent site of peptide biosynthesis for more than 30 years, and many neuropeptides are now known to be common to gut and brain.... (Review)
Review
The brain has been recognized as a prominent site of peptide biosynthesis for more than 30 years, and many neuropeptides are now known to be common to gut and brain. With these precedents in mind it is remarkable that adipose-derived peptides like leptin have attracted minimal attention as brain-derived putative neuromodulators of energy balance. This review outlines the evidence that several adipose-specific genes are also expressed in the central nervous system and pituitary gland. We, and others, confirmed that the genes for leptin, resistin, adiponectin, FIAF (fasting-induced adipose factor) and adiponutrin are expressed and regulated in these tissues. For example, leptin mRNA was readily detectable in human, rat, sheep and pig brain, but not in the mouse. Leptin expression in rat brain and pituitary was regulated through development, by food restriction, and following traumatic brain injury. In contrast, hypothalamic resistin mRNA was unaffected by age or by fasting, but was significantly depleted by food restriction in mouse pituitary gland. Similar results were seen in the ob/ob mouse, and we noted a marked reduction in resistin-positive hypothalamic nerve fibres. Resistin and fiaf mRNA were also upregulated in hypoxic/ischaemic mouse brain. Our studies on the regulation of neuronal adipokines were greatly aided by the availability of clonal hypothalamic neuronal cell lines. One of these, N-1, expresses both rstn and fiaf together with several other neuropeptides and receptors involved in energy homeostasis. Selective silencing of rstn revealed an autocrine/paracrine regulatory system, mediated through socs-3 expression that may influence the feedback effects of insulin and leptin in vivo. A similar convergence of signals in the pituitary gland could also influence anterior pituitary hormone secretion. In conclusion, the evidence is suggestive that brain and pituitary-derived adipokines represent a local regulatory circuit that may fine tune the feedback effects of adipose hormones in the control of energy balance.
Topics: Adiponectin; Animals; Brain; Energy Metabolism; Gene Expression; Gene Expression Regulation; Humans; Leptin; Membrane Proteins; Peptide Hormones; Pituitary Gland; Resistin
PubMed: 17878708
DOI: 10.1159/000108635 -
Journal of Diabetes Research 2014The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the... (Review)
Review
The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.
Topics: Adipokines; Adipose Tissue; Animals; Cytokines; Down-Regulation; Evidence-Based Medicine; Exercise; Humans; Insulin Resistance; Metabolic Syndrome; Motor Activity; Up-Regulation
PubMed: 24563869
DOI: 10.1155/2014/726861 -
Progress in Molecular Biology and... 2015Skeletal muscle and white adipose tissue are the largest organs in the human body and both tissues act as endocrine organs capable of secreting many bioactive molecules.... (Review)
Review
Skeletal muscle and white adipose tissue are the largest organs in the human body and both tissues act as endocrine organs capable of secreting many bioactive molecules. There has been some confusion about nomenclature and we suggest that the name myokine should be restricted to a protein or molecule secreted from myocytes, whereas the term adipokine should be used to describe proteins and molecules secreted from adipocytes. In fact, many myokines are also produced by adipocytes and we propose to name them adipo-myokines. Many adipo-myokines produced by skeletal muscle or adipose tissue are influenced by exercise. Therefore, it is likely that adipo-myokines may contribute in the mediation of the health benefits of exercise and physical inactivity probably leads to an altered adipo-myokine profile, which could provide a potential mechanism for the association between sedentary behavior and many chronic diseases. Within this review, we evaluate the effects of acute and chronic exercise on myokine, adipokine, and adipo-myokine production. By using the adipo-myokine concept and including both skeletal muscle and adipose tissue, an attempt is made to gain a global view on the beneficial effects of different exercise programs and the underlying pathways.
Topics: Adipokines; Animals; Cytokines; Exercise; Humans; Models, Biological; Muscle, Skeletal
PubMed: 26477920
DOI: 10.1016/bs.pmbts.2015.07.002 -
Clinical Science (London, England :... Mar 2021The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies... (Review)
Review
The global obesity epidemic is a major contributor to chronic disease and disability in the world today. Since the discovery of leptin in 1994, a multitude of studies have characterized the pathological changes that occur within adipose tissue in the obese state. One significant change is the dysregulation of adipokine production. Adipokines are an indispensable link between metabolism and optimal immune system function; however, their dysregulation in obesity contributes to chronic low-grade inflammation and disease pathology. Herein, I will highlight current knowledge on adipokine structure and physiological function, and focus on the known roles of these factors in the modulation of the immune response. I will also discuss adipokines in rheumatic and autoimmune diseases.
Topics: Adipokines; Adipose Tissue; Animals; Autoimmunity; Humans; Inflammation; Obesity
PubMed: 33729498
DOI: 10.1042/CS20200895 -
Nature Structural & Molecular Biology Apr 2023The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and...
The adipokine Leptin activates its receptor LEP-R in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility and cancer. However, the structure and mechanism of Leptin-mediated LEP-R assemblies has remained unclear. Intriguingly, the signaling-competent isoform of LEP-R is only lowly abundant amid several inactive short LEP-R isoforms contributing to a mechanistic conundrum. Here we show by X-ray crystallography and cryo-EM that, in contrast to long-standing paradigms, Leptin induces type I cytokine receptor assemblies featuring 3:3 stoichiometry and demonstrate such Leptin-induced trimerization of LEP-R on living cells via single-molecule microscopy. In mediating these assemblies, Leptin undergoes drastic restructuring that activates its site III for binding to the Ig domain of an adjacent LEP-R. These interactions are abolished by mutations linked to obesity. Collectively, our study provides the structural and mechanistic framework for how evolutionarily conserved Leptin:LEP-R assemblies with 3:3 stoichiometry can engage distinct LEP-R isoforms to achieve signaling.
Topics: Leptin; Adipokines; Protein Isoforms; Signal Transduction
PubMed: 36959263
DOI: 10.1038/s41594-023-00941-9 -
Current Molecular Medicine Aug 2010Adipose tissue is an endocrine organ able to produce a wide series of pleiotropic molecules, defined "adipokines". In addition to the regulation of food intake and... (Review)
Review
Adipose tissue is an endocrine organ able to produce a wide series of pleiotropic molecules, defined "adipokines". In addition to the regulation of food intake and energy metabolism, adipokines are also implicated in the complex control of bone biology and specifically of bone remodeling. Leptin, the most studied adipokine, promotes satiety and energy expenditure and its circulating levels are proportional to fat mass. Some paradoxical findings originally suggested the involvement of leptin in controlling bone mass. For example, obese postmenopausal women, with elevated circulating leptin and leptin resistance, appear protected against the development of osteoporosis. Moreover, genetically leptin-deficient mice, which are hypogonadal and obese, display a decreased trabecular volume in long bones, but an increased vertebral bone mass, which is reduced by leptin administration. The complex mechanisms of leptin regulation of bone mass appear to involve selected hypothalamic neuronal populations and the sympathetic outflow, with an important role of osteoblastic beta2-adrenergic receptors. Adiponectin is another adipokine, which promotes insulin sensitivity and is reduced in obese and diabetic subjects. Adiponectin appears to exert a negative effect on bone mass and seems to be an independent predictor of lower bone mass. Although the adipokines resistin and visfatin do not seem to significantly affect bone metabolism, the potential impact of them and other adipokines is still to be determined. Moreover, the molecular adipokine-bone interactions should also be considered in the context of the adipokine changes observed in diseases such as obesity and the metabolic syndrome.
Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Osteoporosis; Resistin
PubMed: 20642443
DOI: 10.2174/1566524011009060522 -
Molecules (Basel, Switzerland) Jan 2022Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered... (Review)
Review
Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.
Topics: Adipokines; Animals; Humans; Metabolic Syndrome
PubMed: 35056647
DOI: 10.3390/molecules27020334 -
Journal of Lipid Research Oct 2019The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more... (Review)
Review
The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more adipose tissue-secreted signaling mediators (adipokines) have been identified since then, and much has been learned about how adipose tissue communicates with other organs of the body to maintain systemic homeostasis. Beyond proteins, additional factors, such as lipids, metabolites, noncoding RNAs, and extracellular vesicles (EVs), released by adipose tissue participate in this process. Here, we review the diverse signaling mediators and mechanisms adipose tissue utilizes to relay information to other organs. We discuss recently identified adipokines (proteins, lipids, and metabolites) and briefly outline the contributions of noncoding RNAs and EVs to the ever-increasing complexities of adipose tissue inter-organ communication. We conclude by reflecting on central aspects of adipokine biology, namely, the contribution of distinct adipose tissue depots and cell types to adipokine secretion, the phenomenon of adipokine resistance, and the capacity of adipose tissue to act both as a source and sink of signaling mediators.
Topics: Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Lipid Metabolism; Signal Transduction
PubMed: 31209153
DOI: 10.1194/jlr.R094060